WorldWideScience

Sample records for sor ligand environment

  1. SOR-ring failure

    International Nuclear Information System (INIS)

    Kitamura, Hideo

    1981-01-01

    It was in the autumn of 1976 that the SOR-ring (synchrotron radiation storage ring) has commenced the regular operation. Since then, the period when the operation was interrupted due to the failures of SOR-ring itself is in total about 8 weeks. Failures and accidents have occurred most in the vacuum system. Those failure experiences are described on the vacuum, electromagnet, radio-frequency acceleration and beam transport systems with their interrupted periods. The eleven failures in the vacuum system have been reported, such as bellows breakage in a heating-evacuating period, leakage from the bellows of straight-through valves (made in U.S.A. and Japan), and leakage from the joint flange of the vacuum system. The longest interruption was 5 weeks due to the failure of a domestically manufactured straight-through valve. The failures of the electromagnet system involve the breakage in a cooling water system, short circuit of a winding in the Q magnet power transformer, blow of a fuse protecting the deflection magnet power source by the current less than the rating, and others. The failures of the RF acceleration system include the breakage of an output electronic tube the breakage of a cavity ceramic, RF voltage fluctuation due to the contact deterioration at a cavity electrode, and the failure of grid bias power source. It is necessary to select the highly reliable components for the vacuum system because the vacuum system failures require longer time for recovery, and very likely to induce secondary and tertiary failures. (Wakatsuki, Y.)

  2. SOR Users` Guide : How to Navigate Through the SOR Analysis.

    Energy Technology Data Exchange (ETDEWEB)

    United States. Bonneville Power Administration.

    1996-08-01

    The Columbia River System Operation Review (SOR) gave river managers, users, and the general public a chance to examine system operations in detail, to study how each river use affects others, and to consider the consequences of changing the way the system works. The task was enormous, and it was a multiyear undertaking. In its wake, the SOR left a multitude of documents and six years of analysis that can and should be used broadly for other reference and research purposes. This catalog will introduce you to numerous SOR products to be found throughout the 20 appendices and the Final Environmental Impact Statement (EIS) Main Report. They include maps, models, data bases, current descriptions of Federal hydro projects and river resources, publications, and slide shows.

  3. Characterization of Lipoprotein Lipases interactions with Sortilin and SorLA

    DEFF Research Database (Denmark)

    Klinger, Stine Christensen

    and regulation of both ligands, as well as to increase the understanding of SorLA’s and sortilin’s functions. Sortilin and SorLA were both shown to bind apolipoprotein A-V at the cell surface and mediate endocytosis. Apolipoprotein A-V trafficking could subsequently be followed through early endosomes, the trans-Golgi......LA might be involved in regulation or transport of brain lipoprotein lipase. In summary, this work adds new details to the current knowledge about the functions of SorLA and sortilin. Moreover, it increases our understanding of lipoprotein lipase and apolipoprotein A-V processing and regulation....

  4. New parallel SOR method by domain partitioning

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Dexuan [Courant Inst. of Mathematical Sciences New York Univ., NY (United States)

    1996-12-31

    In this paper, we propose and analyze a new parallel SOR method, the PSOR method, formulated by using domain partitioning together with an interprocessor data-communication technique. For the 5-point approximation to the Poisson equation on a square, we show that the ordering of the PSOR based on the strip partition leads to a consistently ordered matrix, and hence the PSOR and the SOR using the row-wise ordering have the same convergence rate. However, in general, the ordering used in PSOR may not be {open_quote}consistently ordered{close_quotes}. So, there is a need to analyze the convergence of PSOR directly. In this paper, we present a PSOR theory, and show that the PSOR method can have the same asymptotic rate of convergence as the corresponding sequential SOR method for a wide class of linear systems in which the matrix is {open_quotes}consistently ordered{close_quotes}. Finally, we demonstrate the parallel performance of the PSOR method on four different message passing multiprocessors (a KSR1, the Intel Delta, an Intel Paragon and an IBM SP2), along with a comparison with the point Red-Black and four-color SOR methods.

  5. SOR/83-77, Physical Security Regulations

    International Nuclear Information System (INIS)

    1983-01-01

    These Regulations establish and require the maintenance of security systems, equipment and procedures to implement Canada's international obligations regarding security at those nuclear facilities. The Regulations, which determine the different areas in a nuclear facility, provide for the establishment of security barriers around the ''protected areas'' occupied by facilities and prescribe that the licensees (operators) are required to keep the facilities for which they hold a licence under constant surveillance. They must also make arrangements for a response force - a local, provincial or federal police force detachment or similar force - to provide assistance where necessary. No person may enter a protected area without written authorization from the licensee concerned. Inspectors appointed under the Atomic Energy Control Regulations or designated under an agreement between Canada and the IAEA may be granted an authorization to enter such areas to discharge their duties. The Regulations have been amended by SOR/84-81 of 12 January 1988 to add certain requirements concerning documentary evidence and the duties of the board; by SOR/85-1016 of 25 October 1985 to revise the definition of response force and provide other clarifications; by SOR/91-585 of 10 October 1991 to clarify wording in French. (NEA)

  6. SOR Lithography in West Germany

    Science.gov (United States)

    Heuberger, Anton

    1989-08-01

    The 64 Mbit DRAM will represent the first generation of integrated circuits which cannot be produced reasonably by means of optical lithography techniques. X-ray lithography using synchrotron radiation seems to be the most promising method in overcoming the problems in the sub-0.5 micron range. The first year of production of the 64 Mbit DRAM will be 1995 or 1996. This means that X-ray lithography has to show its applicability in an industrial environment by 1992 and has to prove that the specifications of a 64 Mbit DRAM technology can actually be achieved. Part of this task is a demonstration of production suitable equipment such as the X-ray stepper, including an appropriate X-ray source and measurement and inspection tools. The most important bottlenecks on the way toward reaching these goals are linked to the 1 x scale mask technology, especially the pattern definition accuracy and zero level of printing defects down to the order of magnitude of 50 nm. Specifically, fast defect detection methods on the basis of high resolution e-beam techniques and repair methods have to be developed. The other problems of X-ray lithography, such as high quality single layer X-ray resists, X-ray sources and stepper including alignment are either well on the way or are already solved.

  7. Sor Juana and her library world

    OpenAIRE

    Blásquez, Elsa Barberena

    2000-01-01

    There has been numerous documents about Sor Juana since Juan Camacho published his first volume in Madrid in 1689, and more so during 1995, her anniversary. There is no certainty about the date of her birth, it is placed between 1651 and 1653, she died in 1695. The magazines A BSIDE. REVISTA DE CULTURA MEXICANA during the period 1941-1973 published 25 articles, and CONTEMPORÂNEOS eight articles from 1929 to 1931; the BOLETIN DE LA BIBLIOTECA NACIONAL published five articles in 1951 and I960, ...

  8. The Queen's Two Bodies: Sor Juana and New Spain's Vicereines

    Science.gov (United States)

    Thomas, George Anthony

    2009-01-01

    The work of Sor Juana Ines de la Cruz contains many examples of positive representations of the Queens of Spain and the Vicereines of New Spain. These poetic portraits serve to counter the primarily misogynistic portrayals of ruling women of the seventeenth century. Most importantly, Sor Juana increased the visibility of the vicereine in colonial…

  9. Sor Juana and Nicholas of Cusa

    Directory of Open Access Journals (Sweden)

    Rocío Olivares Zorrilla

    2014-11-01

    Full Text Available Without evaluating the extraordinary and consistent impression that Nicholas of Cusa exerted on the works by Sor Juana Inés de la Cruz, it would be hardly possible to achieve a profound comprehension of one of the most prominent women writers of the Latin American Baroque period. The Cusan’s legacy provided Sor Juana with the symbol of the opposing pyramids of light and shadow, and with the metaphor of the circle and the center, already sifted by the Spanish mystics. Both symbols in her poem The Dream inscribe within a Renaissance change of episteme, in which a mathematical and optical version of the ideas was always produced through the elucidation of oneself, of the individual as part of a cyclic, spherical universe in which a central, all-seeing eye is described in various works by Nicholas of Cusa. The idea of divine contemplation with our bodily eyes closed, for the incorporeal is only accessible by getting rid of the corporeal; the mathematical and geometrical speculations about divinity and the conceptions of the world as a combination of signs; how the infinite and the finite encounter and the knowledge of the world is always a probability and a conjecture, all these are philosophical traces which enlighten The Dream, one of the most captivating intellectual poems in Spanish literature.

  10. Deconvolution of astronomical images using SOR with adaptive relaxation.

    Science.gov (United States)

    Vorontsov, S V; Strakhov, V N; Jefferies, S M; Borelli, K J

    2011-07-04

    We address the potential performance of the successive overrelaxation technique (SOR) in image deconvolution, focusing our attention on the restoration of astronomical images distorted by atmospheric turbulence. SOR is the classical Gauss-Seidel iteration, supplemented with relaxation. As indicated by earlier work, the convergence properties of SOR, and its ultimate performance in the deconvolution of blurred and noisy images, can be made competitive to other iterative techniques, including conjugate gradients, by a proper choice of the relaxation parameter. The question of how to choose the relaxation parameter, however, remained open, and in the practical work one had to rely on experimentation. In this paper, using constructive (rather than exact) arguments, we suggest a simple strategy for choosing the relaxation parameter and for updating its value in consecutive iterations to optimize the performance of the SOR algorithm (and its positivity-constrained version, +SOR) at finite iteration counts. We suggest an extension of the algorithm to the notoriously difficult problem of "blind" deconvolution, where both the true object and the point-spread function have to be recovered from the blurred image. We report the results of numerical inversions with artificial and real data, where the algorithm is compared with techniques based on conjugate gradients. In all of our experiments +SOR provides the highest quality results. In addition +SOR is found to be able to detect moderately small changes in the true object between separate data frames: an important quality for multi-frame blind deconvolution where stationarity of the object is a necesessity.

  11. Set of rules SOR 2 reactor site criteria

    International Nuclear Information System (INIS)

    1976-06-01

    The purpose of this set of rules is to describe criteria which guide the Director in his evaluation of the suitability of proposed sites for stationary power and testing reactors subject to SOR 2. (B.G.)

  12. Water oxidation catalyzed by mononuclear ruthenium complexes with a 2,2'-bipyridine-6,6'-dicarboxylate (bda) ligand: how ligand environment influences the catalytic behavior.

    Science.gov (United States)

    Staehle, Robert; Tong, Lianpeng; Wang, Lei; Duan, Lele; Fischer, Andreas; Ahlquist, Mårten S G; Sun, Licheng; Rau, Sven

    2014-02-03

    A new water oxidation catalyst [Ru(III)(bda)(mmi)(OH2)](CF3SO3) (2, H2bda = 2,2'-bipyridine-6,6'-dicarboxylic acid; mmi = 1,3-dimethylimidazolium-2-ylidene) containing an axial N-heterocyclic carbene ligand and one aqua ligand was synthesized and fully characterized. The kinetics of catalytic water oxidation by 2 were measured using stopped-flow technique, and key intermediates in the catalytic cycle were probed by density functional theory calculations. While analogous Ru-bda water oxidation catalysts [Ru(bda)L2] (L = pyridyl ligands) are supposed to catalyze water oxidation through a bimolecular coupling pathway, our study points out that 2, surprisingly, undergoes a single-site water nucleophilic attack (acid-base) pathway. The diversion of catalytic mechanisms is mainly ascribed to the different ligand environments, from nonaqua ligands to an aqua ligand. Findings in this work provide some critical proof for our previous hypothesis about how alternation of ancillary ligands of water oxidation catalysts influences their catalytic efficiency.

  13. Voltage Sag Compensator for CAR and SOR of HANARO

    International Nuclear Information System (INIS)

    Kim, Hyung-Kyoo; Jung, Hoan-Sung; Wu, Jong-Sup

    2007-01-01

    HANARO is designed so as to be tripped automatically by insertion of control absorber rods(CAR) and shut-off rods(SOR) and the process systems, such as primary cooling system, secondary cooling system and reflector cooling system, etc., stop whenever the off-site power failure occurs, the reactor trips automatically. When voltage sag or momentary interruption occurs, the process systems are in operation but the reactor has an unwanted trip by insertion of CARs and SORs. We installed the voltage sag compensator on the power supply for CARs and SORs so as to prevent a nuisance trip. The compensated time is decided not to exceed 1 sec in consideration of reactor safety. This paper is concerned with the impact of the momentary interruption on the reactor and the effect of the voltage sag compensator

  14. Ultrafiltration technique in conjunction with competing ligand exchange method for Ni–humics speciation in aquatic environment

    Digital Repository Service at National Institute of Oceanography (India)

    Chakraborty, P.; Boissel, M.; Reuillon, A.; Babu, P.V.R.; Parthiban, G.

    The combination of ultrafiltration technique with competing ligand exchange method provides a better understanding of interactions between Ni and different molecular weight fractions of humic acid (HA) at varying pH in aquatic environment...

  15. A comparison theorem for the SOR iterative method

    Science.gov (United States)

    Sun, Li-Ying

    2005-09-01

    In 1997, Kohno et al. have reported numerically that the improving modified Gauss-Seidel method, which was referred to as the IMGS method, is superior to the SOR iterative method. In this paper, we prove that the spectral radius of the IMGS method is smaller than that of the SOR method and Gauss-Seidel method, if the relaxation parameter [omega][set membership, variant](0,1]. As a result, we prove theoretically that this method is succeeded in improving the convergence of some classical iterative methods. Some recent results are improved.

  16. Voltage sags impact on CAR and SOR of HANARO

    International Nuclear Information System (INIS)

    Kim, Hyung Kyoo; Jung, Hoan Sung; Wu, Jong Sup

    2004-01-01

    The combination of the unstable electric power and sensitive equipment may cause the nuisance of reactor trip. The reactor is tripped by the RRS and RPS during the occurrence of the voltage sags or momentary interruptions. We tested the components of RRS and RPS for the immunity from voltage sags and momentary interruptions. The tested components are DC power supply for CAR (control absorbed rod) of RRS and AC coil contactor for SOR (shut off rod) of RPS. We briefly describe the power quality standard for the voltage sags. This paper summarizes the magnitudes and durations of the voltage sags which impact on the CAR and SOR system

  17. SOR/72-43 Radiation Emitting Devices Regulations

    International Nuclear Information System (INIS)

    1972-01-01

    These Regulations of 10 February 1972, supplemented by SOR/77-895, lay down the classes of radiation emitting devices for the purposes of the Radiation Emitting Devices Act. They lay down their standards of design and construction and warning sign specifications and provide for the procedure to be followed by inspectors of such devices. The devices include inter alia extra-oral dental x-ray equipment, baggage inspection x-ray devices, laser scanners, television receivers. (NEA)

  18. Regulation of sorLA in general and in Alzheimer's disease

    DEFF Research Database (Denmark)

    Andersen, Olav Michael; Poulsen, Annemarie Svane Aavild; Zole, Egija

    Background: The Sortillin-related receptor (sorLA) is involved in cellular trafficking and processing of the Amyloid precursor protein (APP). A decrease in sorLA expression has been identified in brain tissue from patients suffering from Alzheimer's disease (AD), suggesting that sorLA may be a key...... tissue from patients with Alzheimer's disease. Conclusions: We have investigated the regulation of sorLA expression and identified several cis - and trans -regulatory elements important for the proper expression of sorLA. These studies may help to elucidate the mechanisms underlying the observ ed down...... regulation of sorLA and the linkage to disease onset of SORL1 SNPs in AD patients....

  19. Petrography and geochemistry of rocks from the sor-rondane mountains, droning Maude land, eastern Antarctica

    International Nuclear Information System (INIS)

    Rehman, S.S.; Shah, M.T.; Jan, M.Q.; Majid, M.

    1999-01-01

    Mamyu rock specimens, were collected from the sor-rondane mountains and Breid Bay area of Drojnning Maud land, eastern Antarctica, during the 2nd Pakistan Antarctic Expedition, 1992-93. Petrography and geochemical studies suggest that the rocks are essentially of igneous origin. The samples dredged from ocean bottom include olivine basalt, amygdaloidal volcanics, dacites and rhyodacites. A majority of these rocks are calc-alkaline and formed by the fraction of olivine, clinopyroxene and plagioclase +- titanomagnetite. Most of these rocks apparently formed in an island arc or continental margin set up. However, volcanics showing ocean floor basalt character are also present. A metamorphosed and deformed basement consisting of amphibolites, calc-silicate rocks and gneisses is intrude by under formed or only slightly deformed granites with a minor arkosic sandstone cover. The granites are chemically distinguished as I-type, originate at deeper crystal level by collisional/subduction related processes during organic environments. (author)

  20. Recognition of GPCRs by peptide ligands and membrane compartments theory: structural studies of endogenous peptide hormones in membrane environment.

    Science.gov (United States)

    Sankararamakrishnan, Ramasubbu

    2006-04-01

    One of the largest family of cell surface proteins, G-protein coupled receptors (GPCRs) regulate virtually all known physiological processes in mammals. With seven transmembrane segments, they respond to diverse range of extracellular stimuli and represent a major class of drug targets. Peptidergic GPCRs use endogenous peptides as ligands. To understand the mechanism of GPCR activation and rational drug design, knowledge of three-dimensional structure of receptor-ligand complex is important. The endogenous peptide hormones are often short, flexible and completely disordered in aqueous solution. According to "Membrane Compartments Theory", the flexible peptide binds to the membrane in the first step before it recognizes its receptor and the membrane-induced conformation is postulated to bind to the receptor in the second step. Structures of several peptide hormones have been determined in membrane-mimetic medium. In these studies, micelles, reverse micelles and bicelles have been used to mimic the cell membrane environment. Recently, conformations of two peptide hormones have also been studied in receptor-bound form. Membrane environment induces stable secondary structures in flexible peptide ligands and membrane-induced peptide structures have been correlated with their bioactivity. Results of site-directed mutagenesis, spectroscopy and other experimental studies along with the conformations determined in membrane medium have been used to interpret the role of individual residues in the peptide ligand. Structural differences of membrane-bound peptides that belong to the same family but differ in selectivity are likely to explain the mechanism of receptor selectivity and specificity of the ligands. Knowledge of peptide 3D structures in membrane environment has potential applications in rational drug design.

  1. The De-Genderization of Knowledge Production: The Case of Sor Juana Ines de la Cruz.

    Science.gov (United States)

    Salazar, Norma

    1994-01-01

    All societies have official knowledge. Life of Sor Juana Ines de la Cruz, 17th-century nun and literary genius, illustrates who discovers knowledge is more important than what knowledge is promulgated. Real issue was not what Sor Juana wrote but whether nun or woman should engage in producing and publishing knowledge. Her efforts have inspired…

  2. A System of Oceanic Reanalysis (SOR) fot the Nordic Seas

    Science.gov (United States)

    Pnyushkov, A.

    2009-04-01

    A system of oceanic reanalysis of the Nordic seas (Norwegian, Greenland and Barents seas) directed to the investigations of long period changes in the oceanic climate of the Arctic sub-polar seas was developed. The system of oceanic reanalysys (SOR) includes hybrid coordinate 22-th level ocean model HYCOM [Bleck,2002] and modern oceanographic data assimilation technique based on spectral nudging method. A series of test experiments was carried out and optimal parameters for assimilation routine were choused. These parameters take into account the accuracy of spatial restoring by means objective analysis procedure and phase distortion in modeling fields during monotonous assimilation of monthly distributions. On the basis of modeling results a set of monthly mean hydrological distributions of thermohaline parameters was created for the Nordic seas that was used for climatic field compilations on the standard levels for period 1957-1990. The data of reanalysis system projections allow us to restore the information about structure and dynamic of oceanographic fields for the periods and areas with a small number of direct measurements, for example East-Greenland currents area, north and north-east parts of the Barents sea. A series of additional experiments with SOR were performed directed to the simple assimilation of sea ice concentration data. A significant improvement of the system of objectively analyzed field preparation was done during 2008 including additional validation procedure of gridded arrays with using the direct data of oceanographic stations. This work was supported by Russian Foundation for Basic Research (grant 07-05-00393).

  3. Nanodisc-Targeted STD NMR Spectroscopy Reveals Atomic Details of Ligand Binding to Lipid Environments.

    Science.gov (United States)

    Muñoz-García, Juan C; Inacio Dos Reis, Rosana; Taylor, Richard J; Henry, Alistair J; Watts, Anthony

    2018-05-18

    Saturation transfer difference (STD) NMR spectroscopy is one of the most popular ligand-based NMR techniques for the study of protein-ligand interactions. This is due to its robustness and the fact that it is focused on the signals of the ligand, without any need for NMR information on the macromolecular target. This technique is most commonly applied to systems involving different types of ligands (e.g., small organic molecules, carbohydrates or lipids) and a protein as the target, in which the latter is selectively saturated. However, only a few examples have been reported where membrane mimetics are the macromolecular binding partners. Here, we have employed STD NMR spectroscopy to investigate the interactions of the neurotransmitter dopamine with mimetics of lipid bilayers, such as nanodiscs, by saturation of the latter. In particular, the interactions between dopamine and model lipid nanodiscs formed either from charged or zwitterionic lipids have been resolved at the atomic level. The results, in agreement with previous isothermal titration calorimetry studies, show that dopamine preferentially binds to negatively charged model membranes, but also provide detailed atomic insights into the mode of interaction of dopamine with membrane mimetics. Our findings provide relevant structural information for the design of lipid-based drug carriers of dopamine and its structural analogues and are of general applicability to other systems. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Linking the environment, DAF-7/TGFβ signaling and LAG-2/DSL ligand expression in the germline stem cell niche.

    Science.gov (United States)

    Pekar, Olga; Ow, Maria C; Hui, Kailyn Y; Noyes, Marcus B; Hall, Sarah E; Hubbard, E Jane Albert

    2017-08-15

    The developmental accumulation of proliferative germ cells in the C. elegans hermaphrodite is sensitive to the organismal environment. Previously, we found that the TGFβ signaling pathway links the environment and proliferative germ cell accumulation. Neuronal DAF-7/TGFβ causes a DAF-1/TGFβR signaling cascade in the gonadal distal tip cell (DTC), the germline stem cell niche, where it negatively regulates a DAF-3 SMAD and DAF-5 Sno-Ski. LAG-2, a founding DSL ligand family member, is produced in the DTC and activates the GLP-1/Notch receptor on adjacent germ cells to maintain germline stem cell fate. Here, we show that DAF-7/TGFβ signaling promotes expression of lag-2 in the DTC in a daf-3- dependent manner. Using ChIP and one-hybrid assays, we find evidence for direct interaction between DAF-3 and the lag-2 promoter. We further identify a 25 bp DAF-3 binding element required for the DTC lag-2 reporter response to the environment and to DAF-7/TGFβ signaling. Our results implicate DAF-3 repressor complex activity as a key molecular mechanism whereby the environment influences DSL ligand expression in the niche to modulate developmental expansion of the germline stem cell pool. © 2017. Published by The Company of Biologists Ltd.

  5. Development of an improved immunoassay for detection of sorLA in cells and biological samples

    DEFF Research Database (Denmark)

    Andersen, Olav Michael; Thakurta, Ishita Guha; West, Mark J.

    Background: SorLA (Sorting - related receptor with A- type repeats) is a 250 kDa type I transmembrane protein, belonging to the VPS10P (vacuolar protein sorting 10 protein) family of neuronal receptors. It is implicated in the development of AD (Alzheimer's Disease), atherosclerosis, diabetic...... retinopathy, and acute leukemia. Despite the overwhelming evidence regarding the role of sorLA in various diseases, there has been a lack of technologies which can precisely quantitate the levels of sorLA in various complex biological matrices. The methods are either qualitative like immunohistochemistry...

  6. Sorção do imazapyr em solos com diferentes texturas Imazapyr sorption in soils with different textures

    Directory of Open Access Journals (Sweden)

    L.E. Firmino

    2008-06-01

    Full Text Available O conhecimento do comportamento de herbicidas no ambiente, sobretudo no solo, permite a predição de possíveis impactos do seu uso em sistemas agrícolas. Com o intuito de avaliar a sorção do herbicida imazapyr no solo, foi realizado um experimento, utilizando sorgo (Sorghum bicolor como planta bioindicadora. A sorção do imazapyr foi avaliada em areia lavada e em três solos, com as seguintes texturas: muito argilosa, franco-argilo-arenosa e areia-franca, provenientes, respectivamente, das cidades de Sete Lagoas, João Pinheiro e Rio Casca, em Minas Gerais. Foram determinados: o valor de I50 (dose que inibiu 50% no acúmulo de massa seca da planta-teste e a relação de sorção [RS = (I50 solo -I 50 areia/I50 areia]. Os valores de I50 observados foram: 29,41; 10,20 e 7,33 mg kg-1, e a relação de sorção (RS: 9,77; 2,73 e 1,68, respectivamente para os solos muito argiloso, franco-argilo-arenoso e areia franca. O herbicida imazapyr apresentou a seguinte ordem de sorção nos substratos: muito argiloso > franco-argilo-arenoso > areia-franca > areia lavada. Em solos arenosos e com baixos teores de matéria orgânica, a baixa sorção do imazapyr predispõe o produto à lixiviação no perfil do solo, podendo contaminar mananciais de águas subterrâneas.Knowledge about herbicide behavior in the environment, especially in soil, allows predicting possible impacts caused by its use in agricultural systems. An experiment using Sorghum bicolor as a bio-indicator was carried out to evaluate imazapyr sorption in soil. Sorption was evaluated in washed sand and in soils of 3 different textures: very clayed, sandy clayed loam and sandy loam, respectively from Sete Lagoas, João Pinheiro and Rio Casca - Minas Gerais. The value of I50, which inhibits 50% of dry biomass accumulation of the test-plant, and sorption relation (SR = I50 soil - I50 sand/I50 sand were determined. I50 values observed were 29.41, 10.20 and 7.33 mg kg-1 and SR values were 9

  7. Synthesis and Characterization of Divalent Manganese, Iron, and Cobalt Complexes in Tripodal Phenolate/N-Heterocyclic Carbene Ligand Environments

    DEFF Research Database (Denmark)

    Käß, Martina; Hohenberger, Johannes; Adelhardt, Mario

    2014-01-01

    . The complete ligand series offers a convenient way of tuning the electronic and steric environment around the metal center, thus, allowing for control of the complex’s reactivity. This series of divalent complexes of Mn, Fe, and Co was synthesized and characterized by 1H NMR, IR, and UV/vis spectroscopy...... as well as by single-crystal X-ray diffraction studies. Variable-temperature SQUID magnetization measurements in the range from 2 to 300 K confirmed high-spin ground states for all divalent complexes and revealed a trend of increasing zero-field splitting |D| from Mn(II), to Fe(II), to Co(II) complexes...

  8. Potential New Ligand Systems for Binding Uranyl Ions in Seawater Environments

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, John [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2014-12-13

    Work began this quarter on a new project involving a combined computational and biosynthetic approach to selective recognition of uranyl ion in aqueous solution. This project exploits the results of computational studies to discover new ligand classes. Synthetic studies will follow to generate target systems for uranyl binding and determination of binding constants. The process will be iterative, with results from computation informing synthesis, and vice versa. The theme of the ligand classes to be examined initially will be biologically based. New phosphonate-containing α-amino acid N-carboxyanhydride (NCA) monomers were used recently to prepare well-defined phosphonate-containing poly-peptides and block copolypeptides. Our first approach is to utilize these phosphate- and phosphonate-containing NCAs for the coordination of uranyl. The work includes the laboratory-scale preparation of a series of NCAs and the full thermodynamic and spectroscopic characterization of the resulting uranyl complexes. We are also evaluating the sequestering activity in different physiological and environmental conditions of these copolymers as well as their biodegradability.

  9. Georges et les trésors du cosmos

    CERN Document Server

    Hawking, Lucy; Parsons, Gary

    2011-01-01

    Les voisins excentriques de Georges, Annie et Eric, ont déménagé en Floride à l'agence Spatiale Globale. Là-bas, Eric s'occupe de son nouveau robot, Homer, qui doit détécter les signes de vie sur Mars. Mais bientôt, Georges reçoit un e-mail : Annie lui demande de la rejoindre au plus vite pour une " mission cosmique " secrète. La jeune fille est persuadée qu'il se passe de drôles de choses sur Mars, car Homer vient de recevoir un message extraterrestre ! Georges et Anne (avec l'aide d'Emmett, un petit garçon bizarre) décident de réparer Cosmos, leur super-ordinateur, et d'aller voir par eux-mêmes... Emmaillotés dans des combinaisons spéciales, ils se lancent alors dans une fabuleuse chasse aux trésors sur Mars, sur les lunes de Saturne, puis sur Titan, avant de se perdre en orbite autour d'Alpha Centauri B... Mais avant de pouvoir élucider le mystère du message extraterrestre, Georges et Annie devront se livrer à une bataille spatiale acharnée qui mettra leur vie en danger, ainsi que ce...

  10. REDOR NMR Reveals Multiple Conformers for a Protein Kinase C Ligand in a Membrane Environment

    Directory of Open Access Journals (Sweden)

    Hao Yang

    2018-01-01

    Full Text Available Bryostatin 1 (henceforth bryostatin is in clinical trials for the treatment of Alzheimer’s disease and for HIV/AIDS eradication. It is also a preclinical lead for cancer immunotherapy and other therapeutic indications. Yet nothing is known about the conformation of bryostatin bound to its protein kinase C (PKC target in a membrane microenvironment. As a result, efforts to design more efficacious, better tolerated, or more synthetically accessible ligands have been limited to structures that do not include PKC or membrane effects known to influence PKC–ligand binding. This problem extends more generally to many membrane-associated proteins in the human proteome. Here, we use rotational-echo double-resonance (REDOR solid-state NMR to determine the conformations of PKC modulators bound to the PKCδ-C1b domain in the presence of phospholipid vesicles. The conformationally limited PKC modulator phorbol diacetate (PDAc is used as an initial test substrate. While unanticipated partitioning of PDAc between an immobilized protein-bound state and a mobile state in the phospholipid assembly was observed, a single conformation in the bound state was identified. In striking contrast, a bryostatin analogue (bryolog was found to exist exclusively in a protein-bound state, but adopts a distribution of conformations as defined by three independent distance measurements. The detection of multiple PKCδ-C1b-bound bryolog conformers in a functionally relevant phospholipid complex reveals the inherent dynamic nature of cellular systems that is not captured with single-conformation static structures. These results indicate that binding, selectivity, and function of PKC modulators, as well as the design of new modulators, are best addressed using a dynamic multistate model, an analysis potentially applicable to other membrane-associated proteins.

  11. Binding of canonical Wnt ligands to their receptor complexes occurs in ordered plasma membrane environments.

    Science.gov (United States)

    Sezgin, Erdinc; Azbazdar, Yagmur; Ng, Xue W; Teh, Cathleen; Simons, Kai; Weidinger, Gilbert; Wohland, Thorsten; Eggeling, Christian; Ozhan, Gunes

    2017-08-01

    While the cytosolic events of Wnt/β-catenin signaling (canonical Wnt signaling) pathway have been widely studied, only little is known about the molecular mechanisms involved in Wnt binding to its receptors at the plasma membrane. Here, we reveal the influence of the immediate plasma membrane environment on the canonical Wnt-receptor interaction. While the receptors are distributed both in ordered and disordered environments, Wnt binding to its receptors selectively occurs in more ordered membrane environments which appear to cointernalize with the Wnt-receptor complex. Moreover, Wnt/β-catenin signaling is significantly reduced when the membrane order is disturbed by specific inhibitors of certain lipids that prefer to localize at the ordered environments. Similarly, a reduction in Wnt signaling activity is observed in Niemann-Pick Type C disease cells where trafficking of ordered membrane lipid components to the plasma membrane is genetically impaired. We thus conclude that ordered plasma membrane environments are essential for binding of canonical Wnts to their receptor complexes and downstream signaling activity. © 2017 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  12. Overexpression, purification and crystallization of the tetrameric form of SorC sorbitol operon regulator

    International Nuclear Information System (INIS)

    Sanctis, Daniele de; Rêgo, Ana T.; Marçal, David; McVey, Colin E.; Carrondo, Maria A.; Enguita, Francisco J.

    2007-01-01

    The sorbitol operon regulator from K. pneumoniae has been overexpressed in E. coli, purified and crystallized. Diffraction data were collected to 3.2 Å. The sorbitol operon regulator (SorC) regulates the metabolism of l-sorbose in Klebsiella pneumonia. SorC was overexpressed in Escherichia coli and purified, and crystals were obtained of a tetrameric form. A single crystal showed X-ray diffraction to 3.20 Å. The crystal belongs to space group P2 1 2 1 2 1 , with unit-cell parameters a = 91.6, b = 113.3, c = 184.1 Å. Analysis of the molecular-replacement solution indicates the presence of four SorC molecules in the asymmetric unit

  13. SorLA controls neurotrophic activity by sorting of GDNF and its receptors GFRα1 and RET

    DEFF Research Database (Denmark)

    Glerup, Simon; Lume, Maria; Olsen, Ditte

    2013-01-01

    is targeted to lysosomes and degraded while GFRα1 recycles, creating an efficient GDNF clearance pathway. The SorLA/GFRα1 complex further targets RET for endocytosis but not for degradation, affecting GDNF-induced neurotrophic activities. SorLA-deficient mice display elevated GDNF levels, altered dopaminergic...

  14. APPLE-II type quasi-periodic variably polarizing undulator at HiSOR

    International Nuclear Information System (INIS)

    Sasaki, Shigemi; Miyamoto, Atsushi; Goto, Kiminori

    2012-01-01

    A newly constructed quasi-periodic APPLE-II undulator was installed in the HiSOR ring at Hiroshima Synchrotron Radiation Center, Hiroshima University during the summer shutdown period in 2011. This 1.8 m-long undulator has a period length of 78 mm. In this article, the mechanism of magnetic field generation for various polarization modes of APPLE undulator, the principle of quasi-periodic undulator and the performance of HiSOR QP-APPLE-II undulator are described. (author)

  15. SorCS2 Regulates Dopaminergic Wiring and Is Processed into an Apoptotic Two-Chain Receptor in Peripheral Glia

    DEFF Research Database (Denmark)

    Glerup, Simon; Olsen, Ditte; Vægter, Christian Bjerggaard

    2014-01-01

    Balancing trophic and apoptotic cues is critical for development and regeneration of neuronal circuits. Here we identify SorCS2 as a proneurotrophin (proNT) receptor, mediating both trophic and apoptotic signals in conjunction with p75NTR. CNS neurons, but not glia, express SorCS2 as a single-chain...... behavioral response to amphetamine reminiscent of ADHD. Contrary, in PNS glia, but not in neurons, proteolytic processing produced a two-chain SorCS2 isoform that mediated proNT-dependent Schwann cell apoptosis. Sciatic nerve injury triggered generation of two-chain SorCS2 in p75NTR-positive dying Schwann...... cells, with apoptosis being profoundly attenuated in Sorcs2−/− mice. In conclusion, we have demonstrated that two-chain processing of SorCS2 enables neurons and glia to respond differently to proneurotrophins....

  16. A modified SOR method for the Poisson equation in unsteady free-surface flow calculations.

    NARCIS (Netherlands)

    Botta, E.F.F.; Ellenbroek, Marcellinus Hermannus Maria

    1985-01-01

    Convergence difficulties that sometimes occur if the successive overrelaxation (SOR) method is applied to the Poisson equation on a region with irregular free boundaries are analyzed. It is shown that these difficulties are related to the treatment of the free boundaries and caused by the appearance

  17. Sorting by the cytoplasmic domain of the amyloid precursor protein binding receptor SorLA

    DEFF Research Database (Denmark)

    Nielsen, Morten S; Gustafsen, Camilla; Madsen, Peder

    2007-01-01

    -formation with the amyloid precursor protein it downregulates generation of Alzheimer's disease-associated Abeta-peptide. The receptor is mainly located in vesicles, suggesting a function in protein sorting and transport. Here we examined SorLA's trafficking using full-length and chimeric receptors and find that its...

  18. Jesuit Neo-Scholasticism and "Criollo" Consciousness in Sor Juana's "El martir del sacramento, San Hermenegildo"

    Science.gov (United States)

    Patterson, Charles

    2013-01-01

    Much of the limited scholarship dedicated to Sor Juana's "autos sacramentales" tends to separate them from the "loas" that were meant to introduce them. Critics often exalt the "loas" for the sympathy that they express for indigenous beliefs, while neglecting the "autos" or viewing them as masterful…

  19. Newton-sor iterative method for solving the two-dimensional porous ...

    African Journals Online (AJOL)

    In this paper, we consider the application of the Newton-SOR iterative method in obtaining the approximate solution of the two-dimensional porous medium equation (2D PME). The nonlinear finite difference approximation equation to the 2D PME is derived by using the implicit finite difference scheme. The developed ...

  20. Comparison results on preconditioned SOR-type iterative method for Z-matrices linear systems

    Science.gov (United States)

    Wang, Xue-Zhong; Huang, Ting-Zhu; Fu, Ying-Ding

    2007-09-01

    In this paper, we present some comparison theorems on preconditioned iterative method for solving Z-matrices linear systems, Comparison results show that the rate of convergence of the Gauss-Seidel-type method is faster than the rate of convergence of the SOR-type iterative method.

  1. Sor/88-391, 21 July 1988, uranium mines (Ontario) occupational health and safety regulations, amendment

    International Nuclear Information System (INIS)

    1988-08-01

    These Regulations (SOR/84-435) were made to establish uniformity in the laws governing occupational health and safety in mines in the Province of Ontario. To ensure conformity, the legal references in the Regulations have been amended to accord with the 1987 amendment of the Ontario Occupational Health and Safety Act [fr

  2. Mutation of the His ligand in mitoNEET stabilizes the 2Fe–2S cluster despite conformational heterogeneity in the ligand environment

    Energy Technology Data Exchange (ETDEWEB)

    Conlan, Andrea R.; Paddock, Mark L.; Homer, Christina [University of California at San Diego, La Jolla, CA 92093 (United States); Axelrod, Herbert L.; Cohen, Aina E. [Stanford Synchrotron Radiation Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025 (United States); Abresch, Edward C.; Zuris, John A. [University of California at San Diego, La Jolla, CA 92093 (United States); Nechushtai, Rachel [Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 91904 (Israel); Jennings, Patricia A., E-mail: pajennin@ucsd.edu [University of California at San Diego, La Jolla, CA 92093 (United States)

    2011-06-01

    The spectroscopic and stability properties and X-ray crystal structure of the H87C mutant of the 2Fe–2S ligand mitoNEET are reported. Strikingly, the single point mutation leads to changes in its absorbance and CD spectra and an increase of around sixfold in the stability of the 2Fe–2S clusters over the pH range 5–7. However, the crystal structure of the H87C mutant displays heterogeneity in a few key residues, including the introduced cysteine ligand. Nonetheless, the cluster is highly stabilized from release. MitoNEET is the only identified Fe–S protein localized to the outer mitochondrial membrane and a 1.5 Å resolution X-ray analysis has revealed a unique structure [Paddock et al. (2007 ▶), Proc. Natl Acad. Sci. USA, 104, 14342–14347]. The 2Fe–2S cluster is bound with a 3Cys–1His coordination which defines a new class of 2Fe–2S proteins. The hallmark feature of this class is the single noncysteine ligand His87, which when replaced by Cys decreases the redox potential (E{sub m}) by ∼300 mV and increases the stability of the cluster by around sixfold. Unexpectedly, the pH dependence of the lifetime of the 2Fe–2S cluster remains the same as in the wild-type protein. Here, the crystal structure of H87C mitoNEET was determined to 1.7 Å resolution (R factor = 18%) to investigate the structural basis of the changes in the properties of the 2Fe–2S cluster. In comparison to the wild type, structural changes are localized to the immediate vicinity of the cluster-binding region. Despite the increased stability, Cys87 displays two distinct conformations, with distances of 2.3 and 3.2 Å between the S{sup γ} and the outer Fe of the 2Fe–2S cluster. In addition, Lys55 exhibits multiple conformations in the H87C mutant protein. The structure and distinct characteristics of the H87C mutant provide a framework for further studies investigating the effects of mutation on the properties of the 2Fe–2S cluster in this new class of proteins.

  3. Sorø Klosters kirkegård for lægfolk

    DEFF Research Database (Denmark)

    Rensbro, Henriette

    2012-01-01

    8 of the graves are medieval, as brick coffins are commonly dated from late 12th to 14th century and two other graves are older. According to the Cistercian rule monks were buried without coffins and from what we know about the location of the monasteries cemeteries, it was usually the cemetery...... times. It is far from the first time stone coffin-graves have been discovered and excavated in the site of Sorø Monastery. The first record in Antikvarisk-Topografisk Arkiv is from 1826. The stone coffins are made of bricks travertine or fieldstones. The grave of archbishop and founder of the Cistercian...... convent in Sorø, Absalon (1201) has been opened and examined three times in 1536, 1827 and 1947....

  4. MEDIACIONES DEL YO Y MONSTRUOSIDAD: SOR JUANA O EL "FÉNIX" BARROCO

    Directory of Open Access Journals (Sweden)

    David Solodkow

    2009-04-01

    Full Text Available El siguiente artículo explora uno de los textos más importantes del barroco novohispano titulado "Respuesta a Sor Filotea" (1691 escrito por Sor Juana Inés de la Cruz (16487-1695. El objetivo del artículo es analizar los modos de constitución de la subjetividad (criolla y femenina en la Nueva España y las transacciones discursivas y retóricas utilizadas a tal fin. El artículo también examina las relaciones entre poder, saber y deseo dentro de la ciudad letrada y los dispositivos discursivos de control y resistencia a dicho poder colonial y religioso. El análisis pone de manifiesto la existencia de una subjetividad heterogénea, fragmentaria y en perpetua negociación y tensión con los discursos sociales de la época.The following article explores one of the most important texts of New Spain s Baroque titled "Respuesta a Sor Filotea ", written by Sor Juan Inés de la Cruz. The main objective of the article is to analyze the ways in which female and Creole subjectivity are constructed in New Spain. At the same time, the article explores the discursive and rhetoric transactions involved in the construction of that subjectivity. The article also examines the relationships between power, knowledge and desire within the de colonial lettered city, and the discursive devices of control and resistance to colonial and religious power. The analysis of the text shows the existence of an heterogeneous and fragmentary subjectivity in constant negotiation and tension with the social discourses of that time.

  5. Y682 mutation of amyloid precursor protein promotes endo-lysosomal dysfunction by disrupting APP-SorLA interaction

    Directory of Open Access Journals (Sweden)

    Luca Rosario La Rosa

    2015-04-01

    Full Text Available The intracellular transport and localization of amyloid precursor protein (APP are critical determinants of APP processing and β-amyloid peptide production, thus crucially important for the pathophysiology of Alzheimer’s disease (AD. Notably, the C-terminal Y682ENPTY687 domain of APP binds to specific adaptors controlling APP trafficking and sorting in neurons. Mutation on the Y682 residue to glycine (Y682G leads to altered APP sorting in hippocampal neurons that favors its accumulation in intracellular compartments and the release of soluble APPα. Such alterations induce premature aging and learning and cognitive deficits in APP Y682G mutant mice (APPYG/YG. Here, we report that Y682G mutation affects formation of the APP complex with sortilin-related receptor (SorLA, resulting in endo-lysosomal dysfunctions and neuronal degeneration. Moreover, disruption of the APP/SorLA complex changes the trafficking pathway of SorLA, with its consequent increase in secretion outside neurons. Mutations in the SorLA gene are a prognostic factor in AD, and increases in SorLA levels in cerebrospinal fluid are predictive of AD in humans. These results might open new possibilities in comprehending the role played by SorLA in its interaction with APP and in the progression of neuronal degeneration. In addition, they further underline the crucial role played by Y682 residue in controlling APP trafficking in neurons.

  6. I awake, she slept. Sor Juana Ines and Juan Rulfo or the new Latin American poetic condition

    Directory of Open Access Journals (Sweden)

    Hoover Delgado

    2015-12-01

    Full Text Available The article examines how Sor Juana Ines de la Cruz and Juan Rulfo, in dialogue with the literary tradition –especially with the work of Dante, Gongorism and the modern tradition– build a Latin American poetic condition. To that end, it studies the long oneiric ascent of Sor Juana, in First Dream; and Susana San Juan’s story, in Pedro Paramo. For the analysis, it goes to the concepts of resistance when suffering and the signals to transcendence provided by Maria Zambrano in her reflections on the essential condition of the human. It explains how Sor Juana and Susana San Juan offer such resistance: Sor Juana through the journey of knowledge, the sovereignty of the body, the exposure of the precariousness of life and the metaphor of the ascent; Susana, through the fall, madness and eroticism. Finally, it interprets in both characters, the appropriation of the signs of transcendence: the revaluation of the moment, of dreams and the creation-destruction of the divine. It concludes by showing how Sor Juana takes the momentum that starts in Europe with Montaigne, Bacon, the Renaissance and the Golden Age and proposes significant transformations that allow speaking of a different poetic condition. And how Rulfo, starting from the American mythic-religious condition, the non-place, the ontological indefiniteness, stops at the image of Purgatory: showing there the luminous consciousness, the unleashed eroticism and the sacralized madness of Susana as a relief, a possibility of leakage and human of redemption of the sentence.

  7. Sulfur Oxygenase Reductase (Sor) in the Moderately Thermoacidophilic Leaching Bacteria: Studies in Sulfobacillus thermosulfidooxidans and Acidithiobacillus caldus

    Science.gov (United States)

    Janosch, Claudia; Remonsellez, Francisco; Sand, Wolfgang; Vera, Mario

    2015-01-01

    The sulfur oxygenase reductase (Sor) catalyzes the oxygen dependent disproportionation of elemental sulfur, producing sulfite, thiosulfate and sulfide. Being considered an “archaeal like” enzyme, it is also encoded in the genomes of some acidophilic leaching bacteria such as Acidithiobacillus caldus, Acidithiobacillus thiooxidans, Acidithiobacillus ferrivorans and Sulfobacillus thermosulfidooxidans, among others. We measured Sor activity in crude extracts from Sb. thermosulfidooxidans DSM 9293T. The optimum temperature for its oxygenase activity was achieved at 75 °C, confirming the “thermophilic” nature of this enzyme. Additionally, a search for genes probably involved in sulfur metabolism in the genome sequence of Sb. thermosulfidooxidans DSM 9293T was done. Interestingly, no sox genes were found. Two sor genes, a complete heterodisulfidereductase (hdr) gene cluster, three tetrathionate hydrolase (tth) genes, three sulfide quinonereductase (sqr), as well as the doxD component of a thiosulfate quinonereductase (tqo) were found. Seven At. caldus strains were tested for Sor activity, which was not detected in any of them. We provide evidence that an earlier reported Sor activity from At. caldus S1 and S2 strains most likely was due to the presence of a Sulfobacillus contaminant. PMID:27682113

  8. Custom Coordination Environments for Lanthanoids: Tripodal Ligands Achieve Near-Perfect Octahedral Coordination for Two Dysprosium-Based Molecular Nanomagnets.

    Science.gov (United States)

    Lim, Kwang Soo; Baldoví, José J; Jiang, ShangDa; Koo, Bong Ho; Kang, Dong Won; Lee, Woo Ram; Koh, Eui Kwan; Gaita-Ariño, Alejandro; Coronado, Eugenio; Slota, Michael; Bogani, Lapo; Hong, Chang Seop

    2017-05-01

    Controlling the coordination sphere of lanthanoid complexes is a challenging critical step toward controlling their relaxation properties. Here we present the synthesis of hexacoordinated dysprosium single-molecule magnets, where tripodal ligands achieve a near-perfect octahedral coordination. We perform a complete experimental and theoretical investigation of their magnetic properties, including a full single-crystal magnetic anisotropy analysis. The combination of electrostatic and crystal-field computational tools (SIMPRE and CONDON codes) allows us to explain the static behavior of these systems in detail.

  9. Hacia la obra de Sor Juana Inés de la Cruz

    OpenAIRE

    Ansaldo Briones, Cecilia

    2012-01-01

    El propósito de este caso pedagógico es describir y recopilar la experiencia de una vida dedicada a la enseñanza de la literatura. La precisión se hace sobre la obra de la poeta mexicana colonial Sor Juana Inés de la Cruz, considerada la mayor exponente de las letras de Hispanoamérica hasta la llegada del siglo XX. Su obra es compleja, rica barroca y requiere de un ingreso cuidadoso y pedagógicamente planificado. El encuentro con el Constructivismo y la Pedagogía de la Comprensión le dieron h...

  10. Hacia una interpretación comprensiva de Sor Juana. Tres loas y la cifra del mundo

    OpenAIRE

    Cortijo Ocaña, Antonio

    2016-01-01

    Sor Juana Inés de la Cruz dedica gran parte de su obra al desciframiento del aparente laberinto de la realidad. Como intelectual, se imagina a sí misma como una segunda Proba, en sus funciones de intérprete, traductora y transmisora que, como Atanasio Kircher, ha de establecer correspondencias y similitudes. En Sor Juana América se convierte en tema de análisis y estudio, como puede apreciarse en particular en su Neptuno alegórico y en las loas a sus tres autos sacramentales: El divino Narcis...

  11. Population Aspects of Fishes in Geba and Sor Rivers, White Nile System in Ethiopia, East Africa

    Directory of Open Access Journals (Sweden)

    Simagegnew Melaku

    2017-01-01

    Full Text Available This study was carried out to assess the diversity, condition factor, length-weight relationship, and sex ratio of fishes in Geba and Sor Rivers located in Baro-Akobo Basin, White Nile system within Ethiopia. Fish samples were collected in one wet and one dry season. The length-weight relationships were fitted using power equation for the most abundant species. A total of 348 fish specimens were collected using gillnets and hooks. These were identified into eight species and one Garra sp. representing seven genera and four families. Family Cyprinidae was the most dominant with six species (66.7%. Labeobarbus intermedius, Labeobarbus nedgia, and Labeo cylindricus were the most abundant fish species, respectively, with 60.72%, 16.83%, and 14.66% index of relative importance (IRI. The diversity index was higher for Geba River (H′ = 1.50 than for Sor River (H′ = 1.10. All the three most abundant species had negative allometric growth. Seasonal variations in the mean Fulton condition factor (FCF were statistically significant for L. cylindricus (p<0.05. There was variation in the sex ratio with the females dominating in all the three most abundant species. Further investigation into the fish diversity, food, feeding, and reproductive behaviors of fish species especially in the tributaries of these rivers and their socioeconomic aspects is recommended.

  12. A Pausa Musical como Signo Polissémico na Obra para Guitarra de Fernando Sor

    Directory of Open Access Journals (Sweden)

    Ricardo Iván Barceló Abeijón

    2016-10-01

    Full Text Available Através do estudo de numerosas obras para guitarra do famoso músico Fernando Sor (1778-1839, temos descoberto que este artista, além de usar a pausa musical escrita com o objetivo habitual de indicar uma suspensão temporal do som numa partitura, também tem utilizado ocasionalmente esse símbolo assignando-lhe uma função suplementar não convencional: uma mudança de posição da mão esquerda. No presente artigo apresentamos essa função não evidente, que temos denominado pausa-sinal, exemplificada mediante alguns fragmentos musicais pertinentes.

  13. Formas de abandonar un laberinto: sor Juana y la figura sorjuanina del escritor americano

    Directory of Open Access Journals (Sweden)

    Facundo Ruiz

    2013-11-01

    Full Text Available Tradicionalmente, la figura de sor Juana Inés de la Cruz (1648-1695 ocupa un lugar central en la literatura y la crítica latinoamericanas y –de manera muy especial– mexicanas. Mujer y monja desiguales, poeta e “inteligencia americana” inigualables, esa figura no ha tardado en construir cierto mito en torno de su obra, como cierta “clave” que vela o desvela los caminos que conducen al corazón no sólo de su singular literatura sino de su borrascosa historia. Curiosa pero no casualmente, más de una vez la mexicana –en sus poemas así como en sus cartas– ha desalentado esas imágenes e ideas que son, también o principalmente, las de cierta concepción de la escritura y la lectura. En este sentido, el siguiente artículo se propone trazar las coordenadas de dicho problema (el mito sorjuanino y la desmitificación de sor Juana a fin de deslindar dos aspectos (inseparables de dicho fenómeno: el que hace a la lectura crítica e incluso a la edición y fijación de sus textos; y el que refiere a la concepción y práctica de la literatura en América Latina en uno de sus momentos inaugurales: el siglo XVII, y a través de una de sus figuras más elusivas: la sorjuanina.

  14. Fourth-order numerical solutions of diffusion equation by using SOR method with Crank-Nicolson approach

    Science.gov (United States)

    Muhiddin, F. A.; Sulaiman, J.

    2017-09-01

    The aim of this paper is to investigate the effectiveness of the Successive Over-Relaxation (SOR) iterative method by using the fourth-order Crank-Nicolson (CN) discretization scheme to derive a five-point Crank-Nicolson approximation equation in order to solve diffusion equation. From this approximation equation, clearly, it can be shown that corresponding system of five-point approximation equations can be generated and then solved iteratively. In order to access the performance results of the proposed iterative method with the fourth-order CN scheme, another point iterative method which is Gauss-Seidel (GS), also presented as a reference method. Finally the numerical results obtained from the use of the fourth-order CN discretization scheme, it can be pointed out that the SOR iterative method is superior in terms of number of iterations, execution time, and maximum absolute error.

  15. Report on geological fieldwork in the Sor Rondane Mountains, Eastern Dronning Maud Land, 2008-2009 (JARE-50

    Directory of Open Access Journals (Sweden)

    Masaaki Owada

    2011-07-01

    Full Text Available The Sor Rondane Mountains field party, part of the summer party of the 50th Japanese Antarctic Research Expedition (JARE-50, consisted of five geologists and one field assistant, and conducted geological fieldwork in the western Sr Rondane Mountains, Eastern Dronning Maud Land, as part of a research project of the National Institute of Polar Research (#P-5-1. The field party accessed the mountains using the Dronning Maud Land Air Network (DROMLAN from Cape Town to a runway close to the Belgian base, via the Novolazarevskaya runway. The field party made three campsites (Base Camp, Camp 1, and Camp 3 and stayed on the snowfield for 75 days. Here, we report the detailed operation plans and present a summary of the fieldwork, including information on logistics and weather reports for the western Sor Rondane Mountains.

  16. Sorção de poluentes orgânicos emergentes em lodo de esgoto

    Directory of Open Access Journals (Sweden)

    Simone Bittencourt

    2016-03-01

    Full Text Available RESUMO O uso de lodo de esgoto na agricultura promove a reciclagem de nutrientes e de matéria orgânica, trazendo benefícios ao desenvolvimento vegetal e à conservação do solo e da água. No entanto, é crescente a preocupação com poluentes orgânicos que possam estar no lodo de esgoto. A presença de medicamentos (antibióticos, tranquilizantes, antiepilépticos, hormônios (naturais e sintéticos, perfumes, bactericidas, entre outros poluentes orgânicos, em diferentes compartimentos ambientais é uma questão emergente, devido à escassez de informações sobre o impacto potencial associado à sua ocorrência, seu destino e efeitos ecotoxicológicos. Esses compostos, denominados poluentes orgânicos emergentes, podem ser removidos durante o tratamento de esgoto por degradação, transformação biológica, volatilização e/ou sorção ao lodo. Esses processos são influenciados pelas propriedades físicas e químicas do poluente e pelas condições de tratamento do esgoto. Informações sobre características físico-químicas, como potencial de acidez e hidrofobicidade, são importantes para compreender os mecanismos de remoção e para adoção de medidas que favoreçam a remoção de tais poluentes, como por exemplo a alteração nas condições operacionais e/ou adoção de tecnologias. A presente revisão bibliográfica apresenta as características físico-químicas de poluentes orgânicos emergentes e seu potencial de sorção em lodo de esgoto.

  17. Mujer y escritura en la época de Sor Juana Inés de la Cruz

    Directory of Open Access Journals (Sweden)

    Francisca NOGUEROL JIMÉNEZ

    2009-11-01

    Full Text Available RESUMEN: El artículo rastrea la existencia de escritoras coetáneas a sor Juana Inés de la Cruz que, como la monja mexicana, lucharon contra la alienación a la que eran sometidas por su condición de mujeres escritoras. A través de una serie de estrategias retóricas muy similares a las utilizadas en la «Respuesta a sor Filotea de la Cruz», las españolas María de San José, María de Zayas, la inglesa Mary Astell y la colombiana Francisca Josefa del Castillo, demostraron en distinto grado hasta qué punto el ser humano ha luchado a lo largo de su historia por conformarse como sujeto frente a un pensamiento –en este caso, la misoginia– que frustra sus intentos de expresión.ABSTRACT: This article seeks out the existence of female writers contemporary to sor Juana Inés de la Cruz who, like the Mexican nun, fought against the alienation to which they were subjected by their condition as women writers. Through a series of rethorical strategies very similar to the one’s applied in «Respuesta a sor Filotea de la Cruz», the Spanish women writers María de San José and María de Zayas, the English Mary Astell and the Colombian Francisca Josefa del Castillo demonstrated, to differing degrees, the exent to which human beings have fought throughout history to establish themselves as a subject facing a frame of mind –namely, misogyny–, that frustates their efforts of expression.

  18. Expression of transgenes targeted to the Gt(ROSA26Sor locus is orientation dependent.

    Directory of Open Access Journals (Sweden)

    Douglas Strathdee

    2006-12-01

    Full Text Available Targeting transgenes to a chosen location in the genome has a number of advantages. A single copy of the DNA construct can be inserted by targeting into regions of chromatin that allow the desired developmental and tissue-specific expression of the transgene.In order to develop a reliable system for reproducibly expressing transgenes it was decided to insert constructs at the Gt(ROSA26Sor locus. A cytomegalovirus (CMV promoter was used to drive expression of the Tetracycline (tet transcriptional activator, rtTA2(s-M2, and test the effectiveness of using the ROSA26 locus to allow transgene expression. The tet operator construct was inserted into one allele of ROSA26 and a tet responder construct controlling expression of EGFP was inserted into the other allele.Expression of the targeted transgenes was shown to be affected by both the presence of selectable marker cassettes and by the orientation of the transgenes with respect to the endogenous ROSA26 promoter. These results suggest that transcriptional interference from the endogenous gene promoter or from promoters in the selectable marker cassettes may be affecting transgene expression at the locus. Additionally we have been able to determine the optimal orientation for transgene expression at the ROSA26 locus.

  19. Comparative performance of the conjugate gradient and SOR [Successive Over Relaxation] methods for computational thermal hydraulics

    International Nuclear Information System (INIS)

    King, J.B.; Anghaie, S.; Domanus, H.M.

    1987-01-01

    Finite difference approximations to the continuity, momentum, and energy equations in thermal hydraulics codes result in a system of N by N equations for a problem having N field points. In a three dimensional problem, N increases as the problem becomes larger or more complex, and more rapidly as the computational mesh size is reduced. As a consequence, the execution time required to solve the problem increases, which may lead to placing limits on the problem resolution or accuracy. A conventinal method of solution of these systems of equations is the Successive Over Relaxation (SOR) technique. However, for a wide range of problems the execution time may be reduced by using a more efficient linear equation solver. One such method is the conjugate gradient method which was implemented in COMMIX-1B thermal hydraulics code. It was found that the execution time required to solve the resulting system of equations was reduced by a factor of about 2 for some problems. This paper summarizes the characteristics of these iterative solution procedures and compares their performance in modeling of a variety of reactor thermal hydraulic problems, using the COMMIX-1B computer code

  20. Influência do pH na sorção de imazaquin em um Latossolo Vermelho Acriférrico

    Directory of Open Access Journals (Sweden)

    W. S. D. Rocha

    2000-09-01

    Full Text Available O herbicida imazaquin é uma molécula orgânica com grupos funcionais ionizáveis, sendo sua sorção dependente do pH e da carga elétrica líquida do solo. Neste trabalho, foi estudada a sorção do imazaquin nas camadas superficiais e subsuperficiais de um Latossolo Vermelho Acriférrico típico textura muito argilosa, considerando quatro diferentes valores de pH. Com uso de moléculas radiomarcadas com carbono-14, determinou-se a quantidade sorvida pela diferença entre a quantidade aplicada e a remanescente em solução. Os resultados foram ajustados à equação de Freundlich, para determinação do coeficiente de sorção (Kf. De maneira geral, o herbicida apresentou baixa sorção no solo. Nas amostras coletadas nas duas profundidades, a sorção diminuiu com a elevação do pH. Para um mesmo valor de pH, a sorção foi maior no horizonte subsuperficial do que no superficial, sendo a carga líquida positiva resultante do baixo teor de matéria orgânica e dos elevados conteúdos de óxidos de ferro e de alumínio. Quando a carga elétrica líquida do solo foi positiva, não foi possível predizer a sorção de imazaquin, considerando apenas a especiação da molécula e a sua partição na fração orgânica do solo.

  1. Design and synthesis of a tetradentate '3-amine-1-carboxylate' ligand to mimic the metal binding environment at the non-heme iron(II) oxidase active site.

    Science.gov (United States)

    Dungan, Victoria J; Ortin, Yannick; Mueller-Bunz, Helge; Rutledge, Peter J

    2010-04-07

    Non-heme iron(II) oxidases (NHIOs) catalyse a diverse array of oxidative chemistry in Nature. As part of ongoing efforts to realize biomimetic, iron-mediated C-H activation, we report the synthesis of a new 'three-amine-one-carboxylate' ligand designed to complex with iron(II) and mimic the NHIO active site. The tetradentate ligand has been prepared as a single enantiomer in nine synthetic steps from N-Cbz-L-alanine, pyridine-2,6-dimethanol and diphenylamine, using Seebach oxazolidinone chemistry to control the stereochemistry. X-Ray crystal structures are reported for two important intermediates, along with variable temperature NMR experiments to probe the hindered interconversion of conformational isomers of several key intermediates, 2,6-disubstituted pyridine derivatives. The target ligand and an N-Cbz-protected precursor were each then complexed with iron(II) and tested for their ability to promote alkene dihydroxylation, using hydrogen peroxide as the oxidant.

  2. Report on geomorphologic and geodesic field surveys in the Sor Rondane Mountains, Eastern Dronning Maud Land, 2011-2012 (JARE-53

    Directory of Open Access Journals (Sweden)

    Yusuke Suganuma

    2012-11-01

    Full Text Available Geomorphologic and geodetic field surveys were carried out in the Sor Rondane Mountains, East Dronning Maud Land, Antarctica, during the 2011-2012 summer season as part of the 53rd Japanese Antarctic Research Expedition (JARE-53. The field party consisted of three geomorphologists, one geodesist, and one field assistant. The expedition was supported by the Belgian Antarctic Research Expedition (BELARE and the International Polar Foundation (IPF. Dronning Maud Land Air Network (DROMLAN provided air transport from Cape Town, South Africa to the Sor Rondane Mountains via Novolazarevskaya Airbase. The survey areas were the central and western parts of the Sor Rondane Mountains. This report summarizes the field expedition in terms of operations, logistics, and weather records.

  3. Report on gravity measurements and replacement of an unmanned magnetometer in the Sor Rondane Mountains, Eastern Dronning Maud Land, 2013 (JARE-55

    Directory of Open Access Journals (Sweden)

    Yusuke Suganuma

    2014-11-01

    Full Text Available Gravity measurements, replacement of the unmanned magnetometer, and a reconnaissance flight to the Belgica Mountains were carried out in the Sor Rondane Mountains as a part of the 55 th Japanese Antarctic Research Expedition (JARE-55. The field party comprised two geodesists, one geomorphologists, and one magnetospheric scientist. The Belgian Antarctic Research Expedition (BELARE and International Polar Foundation (IPF supported this field expedition. Dronning Maud Land Air Network (DROMLAN provided airborne access from Cape Town, South Africa to the Sor Rondane Mountains via Novolazarevskaya Airbase. The survey areas of this field expedition are the central parts of the Sor Rondane Mountains and the Belgica Mountains. This report summarizes the field expedition in terms of operations, logistics, and weather observations.

  4. Ontologies and Epistemologies to Achieve Knowledge in Sor Juana Ines de la Cruz’s Poem «Primero Sueño»

    Directory of Open Access Journals (Sweden)

    Lydia Deni Gamboa López

    2017-11-01

    Full Text Available In this article, I propose reading one section of sor Juana Inés de la Cruz’s poem «Primero Sueño» as a philosophical reflexion about the discussion between realists and nominalists, on the one hand, and as a reflexion about the preferable based realist/nominalist methodology on the other hand. The realist perspective presented in this poem has a Platonic-Augustinian character. The nominalist perspective —an ontology which sor Juana seems to have preferred— has an Ockhamist vein.

  5. Benzannulated tris(2-mercapto-1-imidazolyl)hydroborato ligands: tetradentate κ4-S3H binding and access to monomeric monovalent thallium in an [S3] coordination environment.

    Science.gov (United States)

    Rong, Yi; Palmer, Joshua H; Parkin, Gerard

    2014-01-21

    The benzannulated tris(mercaptoimidazolyl)borohydride sodium complex, [Tm(Bu(t)Benz)]Na, has been synthesized via the reaction of NaBH4 with 1-tert-butyl-1,3-dihydro-2H-benzimidazole-2-thione, while [Tm(MeBenz)]K has been synthesized via the reaction of KBH4 with 1-methyl-1,3-dihydro-2H-benzimidazole-2-thione. The molecular structures of the solvated adducts, {[Tm(Bu(t)Benz)]Na(THF)}2(μ-THF)2 and [Tm(MeBenz)]K(OCMe2)3, have been determined by X-ray diffraction, which demonstrates that the [Tm(R)] ligands in these complexes adopt different coordination modes to that in {[Tm(MeBenz)]Na}2(μ-THF)3. Specifically, while the [Tm(MeBenz)] ligand of the sodium complex {[Tm(MeBenz)]Na}2(μ-THF)3 adopts a κ(3)-S3 coordination mode, the potassium complex [Tm(MeBenz)]K(OCMe2)3 adopts a most uncommon inverted κ(4)-S3H coordination mode in which the potassium binds to all three sulfur donors and the hydrogen of the B-H group in a linear KH-B manner. Furthermore, the [Tm(Bu(t)Benz)] ligand of {[Tm(Bu(t)Benz)]Na(THF)}2(μ-THF)2 adopts a κ(3)-S2H coordination mode, thereby demonstrating the flexibility of this ligand system. The monovalent thallium compounds, [Tm(MeBenz)]Tl and [Tm(Bu(t)Benz)]Tl, have been obtained via the corresponding reactions of [Tm(MeBenz)]Na and [Tm(Bu(t)Benz)]Na with TlOAc. X-ray diffraction demonstrates that the three sulfur donors of the [Tm(RBenz)] ligands of both [Tm(MeBenz)]Tl and [Tm(Bu(t)Benz)]Tl chelate to thallium. This coordination mode is in marked contrast to that in other [Tm(R)]Tl compounds, which exist as dinuclear molecules wherein two of the sulfur donors coordinate to different thallium centers. As such, this observation provides further evidence that benzannulation promotes κ(3)-S3 coordination in this system.

  6. The conquered conqueror Álvar Núñez Cabeza de Vaca and the conquered conqueror Sor Juana Inés de la Cruz. Analysis of two divergent identities from two brief works

    Directory of Open Access Journals (Sweden)

    Alejandro Rodríguez Díaz del Real

    2017-11-01

    Full Text Available Starting from two recent critical publications against the fatalism of the traditional discourse of the (anti-Spanish Black Legend, which do not pretend to be revisionist but instead point out certain positive aspects to the conquest of the Americas, the article contrasts two works that illustrate the permeability of two minds who wanted to open up to diversity: Álvar Núnez Cabeza de Vaca with his Shipwrecks (Naufragios on the one hand, and Sor Juana Inés de la Cruz with his Allegorical Neptune (Neptuno alegórico on the other. Only half a century after the discovery of America, and in the exact year of the New Laws of Charles V, which reflect the spirit of Las Casas critics and a defence of the Indian that later landed in the anti-Spanish Black Legend, Cabeza de Vaca presents a case of self-discovery as a fascinated conqueror who ends up conquered by the very environment that he is supposed to dominate; by a world that is too different and mysterious not to arouse his curiosity. The article contrasts this adventure of empathy and knowledge towards the other with an original work by Sor Juana Inés de la Cruz, Neptuno alegórico (1680, which represents another kind of journey, more a literary than autobiographical one, of the American world towards a Baroque or European “otherness”. In spite of the considerable time that separates each case, and of the logical and predictable divergences in terms of literary genre, both works are united by a willingness to be carried away by cultural spheres and aesthetic guidelines that are far from the known world, doing what today we would call “leaving one’s comfort zone”, but achieving an enrichment of the authors’ own lived and creative experience, as well as the literary horizon of the reader.

  7. Educated Guess van gevolgen voor verkeersslachtoffers door maatregel Snorfiets op de rijbaan (SOR) in Amsterdam : een eerste inschatting van effecten gerelateerd aan verkeersveiligheid.

    NARCIS (Netherlands)

    Wijlhuizen, G.J. Dijkstra, A. Bos, N.M. Goldenbeld, C. & Stipdonk, H.L.

    2013-01-01

    Educated Guess about the consequences for casualties as a result of introduction of the measure Light moped in the carriageway (SOR) in Amsterdam : a first estimate of the effects related to road safety. The Board of Mayor and Eldermen of the City of Amsterdam considers moving light mopeds in 50km/h

  8. Seasonal dynamics of common ground beetles (Coleoptera: Carabidae) along an urbanisation gradient near Sorø, Zealand, Denmark

    DEFF Research Database (Denmark)

    Elek, Zoltan; Howe, Andy G.; Enggaard, Mattias

    2017-01-01

    The seasonal activity of six carabid species (Nebria brevicollis, Carabus nemoralis, C. hortensis, C. coriaceus, Pterostichus melanarius and Abax parallelepipedus) was studied along an urbanisation gradient (rural forest – suburban forest – forest fragments in urban park) in Sorø, Denmark, during...... and between the years (C. nemoralis, N. brevicollis and P. melanarius). In four out of six studied species, 2005 was less favourable than 2004. Spring activity in the urban habitat started earlier than in the suburban or forested ones. Abetter understanding of urban green infrastructures in biodiversity...... assessments may need the study of seasonality in order to distinguish whether the bioindicator’s responses are to habitat quality or stochastic seasonal events....

  9. Environment

    DEFF Research Database (Denmark)

    Valentini, Chiara

    2017-01-01

    The term environment refers to the internal and external context in which organizations operate. For some scholars, environment is defined as an arrangement of political, economic, social and cultural factors existing in a given context that have an impact on organizational processes and structures....... For others, environment is a generic term describing a large variety of stakeholders and how these interact and act upon organizations. Organizations and their environment are mutually interdependent and organizational communications are highly affected by the environment. This entry examines the origin...... and development of organization-environment interdependence, the nature of the concept of environment and its relevance for communication scholarships and activities....

  10. Reduction of dinitrogen ligands

    International Nuclear Information System (INIS)

    Richards, R.L.

    1983-01-01

    Processes of dinitrogen ligand reduction in complexes of transition metals are considered. The basic character of the dinitrogen ligand is underlined. Data on X-ray photoelectronic spectroscopy and intensities of bands ν (N 2 ) in IR-spectra of nitrogen complexes are given. The mechanism of protonation of an edge dinitrogen ligand is discussed. Model systems and mechanism of nitrogenogenase are compared

  11. Ligands in PSI structures

    International Nuclear Information System (INIS)

    Kumar, Abhinav; Chiu, Hsiu-Ju; Axelrod, Herbert L.; Morse, Andrew; Elsliger, Marc-André; Wilson, Ian A.; Deacon, Ashley

    2010-01-01

    A survey of the types and frequency of ligands that are bound to PSI structures is analyzed as well as their utility in functional annotation of previously uncharacterized proteins. Approximately 65% of PSI structures report some type of ligand(s) that is bound in the crystal structure. Here, a description is given of how such ligands are handled and analyzed at the JCSG and a survey of the types, variety and frequency of ligands that are observed in the PSI structures is also compiled and analyzed, including illustrations of how these bound ligands have provided functional clues for annotation of proteins with little or no previous experimental characterization. Furthermore, a web server was developed as a tool to mine and analyze the PSI structures for bound ligands and other identifying features

  12. LA CELDA, EL HÁBITO Y LA EVASIÓN EPISTOLAR EN SOR JUANA INÉS DE LA CRUZ

    Directory of Open Access Journals (Sweden)

    Luz Ángela Martínez

    2012-04-01

    Full Text Available Centrado en las representaciones plásticas de Sor Juana Inés de la Cruz, el presente trabajo reflexiona sobre la relación entre la representación del Barroco de Indias y su contexto de producción. A partir de las anteriores coordenadas, revisa la obra de la monja y la orientación epistolar que adquieren sus poemas como forma de evasión de la celda y el hábito.Focused on the visual representations of Sor Juana Inés de la Cruz, this paper reflects on the relationship between the Baroque of the Indies aesthetics and their context o production. Based on the above coordinates, it reviews the nun's work and the epistolary orientation that her poems acquire as a form of escape from the convent and habit.

  13. Mayor gloria de Dios es que lo sea una mujer... Sor María de Jesús de Ágreda y Sor Francisca Josefa de la Concepción del Castillo (sobre la escritura conventual en los siglos XVI y XVII

    Directory of Open Access Journals (Sweden)

    Ferrús Antón, Beatriz

    2008-06-01

    Full Text Available During the 16th and 17th centuries the convents were the best space for women’s writing. A Spanish nun, Sor María de Jesús de Ágreda, and a Latin-American nun, Sor Francisca Josefa de la Concepción del Castillo, are two of the most important writers of that time, and they serve like a example to comment the feminine writing in the convent. The autobiography, as a space for self analysis, receives a special attention.Durante los siglos XVI y XVII, los conventos se convirtieron en el espacio privilegiado para la escritura femenina. Una monja española, Sor María de Jesús de Ágreda, y otra latinoamericana Sor Francisca Josefa de la Concepción del Castillo, autoras de textos de referencia para las letras de su tiempo, nos sirven de ejemplo para analizar las claves de la escritura femenina (conventual durante estos siglos. La narración autobiográfica, como espacio de expresividad y autoanálisis femenino recibe aquí una especial atención.

  14. La monja que conquistó Europa. Sor Juana Inés en la cruz de la crítica // The nun who conquered Europe: Sor Juana Inés on the cross of criticism

    Directory of Open Access Journals (Sweden)

    Emil Volek

    2016-12-01

    Full Text Available The article situates the phenomenon of Sor Juana Inés de la Cruz (1651–1695 within the myth of the “return of the caravels,” invented from the Spanish American side as a proof of parity with the former “Mother Country,” achieved apparently towards the end of the 19th century. However, “caravels” were “returning” much earlier. Based on the author’s book La mujer que quiso ser amada por Dios (The Woman who Wanted to be Loved by God, 2016 and on recent archival discoveries, the study then focuses on the Mexican nun, the history of her publications in Spain during her lifetime, and the consequences of the historical entanglements of her supporters for her literary heritage; finally, it takes to task the surprising generalized shortcomings of the sorjuanista criticism, among others, reading her work out of its internal (“genetic” and external contexts, and not having asked some most elemental questions about her works in both the modern and the ancient editions.

  15. Transcriptional activation of LON Gene by a new form of mitochondrial stress: A role for the nuclear respiratory factor 2 in StAR overload response (SOR).

    Science.gov (United States)

    Bahat, Assaf; Perlberg, Shira; Melamed-Book, Naomi; Isaac, Sara; Eden, Amir; Lauria, Ines; Langer, Thomas; Orly, Joseph

    2015-06-15

    High output of steroid hormone synthesis in steroidogenic cells of the adrenal cortex and the gonads requires the expression of the steroidogenic acute regulatory protein (StAR) that facilitates cholesterol mobilization to the mitochondrial inner membrane where the CYP11A1/P450scc enzyme complex converts the sterol to the first steroid. Earlier studies have shown that StAR is active while pausing on the cytosolic face of the outer mitochondrial membrane while subsequent import of the protein into the matrix terminates the cholesterol mobilization activity. Consequently, during repeated activity cycles, high level of post-active StAR accumulates in the mitochondrial matrix. To prevent functional damage due to such protein overload effect, StAR is degraded by a sequence of three to four ATP-dependent proteases of the mitochondria protein quality control system, including LON and the m-AAA membranous proteases AFG3L2 and SPG7/paraplegin. Furthermore, StAR expression in both peri-ovulatory ovarian cells, or under ectopic expression in cell line models, results in up to 3-fold enrichment of the mitochondrial proteases and their transcripts. We named this novel form of mitochondrial stress as StAR overload response (SOR). To better understand the SOR mechanism at the transcriptional level we analyzed first the unexplored properties of the proximal promoter of the LON gene. Our findings suggest that the human nuclear respiratory factor 2 (NRF-2), also known as GA binding protein (GABP), is responsible for 88% of the proximal promoter activity, including the observed increase of transcription in the presence of StAR. Further studies are expected to reveal if common transcriptional determinants coordinate the SOR induced transcription of all the genes encoding the SOR proteases. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Sorção e dessorção de tiametoxam e atrazina em solo sob diferentes sistemas de manejo

    Directory of Open Access Journals (Sweden)

    Thayne D. Schmidt

    2015-06-01

    Full Text Available RESUMO A sorção e dessorção de agrotóxicos no solo são fatores importantes que contribuem para o processo de retenção, bem como seu destino ambiental e biodisponibilidade. Objetivou-se avaliar a sorção e a dessorção do tiametoxam e atrazina em um Latossolo Vermelho distroférrico típico submetido a diferentes sistemas de manejo em um experimento de longa duração. Os sistemas de manejo do solo avaliados foram convencional, integração lavoura pecuária e plantio direto. Para tal, utilizou-se o método da batelada além de amostras de solo coletadas nas profundidades de 0-10 e 10-30 cm. Observou-se baixa retenção de ambos os agrotóxicos no solo para os sistemas de manejo. Para sorção, considerando ambas as profundidades e todos os sistemas, os valores dos coeficientes de Freundlich variaram de 0,87 a 4,30 L kg-1 para o tiametoxam e de 0,98 a 3,55 L kg-1 para a atrazina. Os expoentes de Freundlich variaram de 0,53 a 1,70 para ambos os compostos considerando-se todas as profundidades e sistemas. Os coeficientes de dessorção foram, em sua maioria, superiores aos de sorção sugerindo a ocorrência do fenômeno de histerese.

  17. Identification of qSOR1, a major rice QTL involved in soil-surface rooting in paddy fields.

    Science.gov (United States)

    Uga, Yusaku; Hanzawa, Eiko; Nagai, Shinsei; Sasaki, Kazuhiro; Yano, Masahiro; Sato, Tadashi

    2012-01-01

    Specific Indonesian lowland rice (Oryza sativa L.) cultivars elongate thick primary roots on the soil surface of paddy fields. To clarify the genetic factors controlling soil-surface rooting, we performed quantitative trait locus (QTL) analyses using 124 recombinant inbred lines (RILs) derived from a cross between Gemdjah Beton, an Indonesian lowland rice cultivar with soil-surface roots, and Sasanishiki, a Japanese lowland rice cultivar without soil-surface roots. These cultivars and the RILs were tested for soil-surface rooting in a paddy field. We identified four regions of chromosomes 3, 4, 6, and 7 that were associated with soil-surface rooting in the field. Among them, one major QTL was located on the long arm of chromosome 7. This QTL explained 32.5-53.6% of the total phenotypic variance across three field evaluations. To perform fine mapping of this QTL, we measured the basal root growth angle of crown roots at the seedling stage in seven BC(2)F(3) recombinant lines grown in small cups in a greenhouse. The QTL was mapped between markers RM21941 and RM21976, which delimit an 812-kb interval in the reference cultivar Nipponbare. We have designated this QTL qSOR1 (quantitative trait locus for SOIL SURFACE ROOTING 1).

  18. Through-container, extremely low concentration detection of multiple chemical markers of counterfeit alcohol using a handheld SORS device.

    Science.gov (United States)

    Ellis, David I; Eccles, Rebecca; Xu, Yun; Griffen, Julia; Muhamadali, Howbeer; Matousek, Pavel; Goodall, Ian; Goodacre, Royston

    2017-09-21

    Major food adulteration incidents occur with alarming frequency and are episodic, with the latest incident, involving the adulteration of meat from 21 producers in Brazil supplied to 60 other countries, reinforcing this view. Food fraud and counterfeiting involves all types of foods, feed, beverages, and packaging, with the potential for serious health, as well as significant economic and social impacts. In the spirit drinks sector, counterfeiters often 'recycle' used genuine packaging, or employ good quality simulants. To prove that suspect products are non-authentic ideally requires accurate, sensitive, analysis of the complex chemical composition while still in its packaging. This has yet to be achieved. Here, we have developed handheld spatially offset Raman spectroscopy (SORS) for the first time in a food or beverage product, and demonstrate the potential for rapid in situ through-container analysis; achieving unequivocal detection of multiple chemical markers known for their use in the adulteration and counterfeiting of Scotch whisky, and other spirit drinks. We demonstrate that it is possible to detect a total of 10 denaturants/additives in extremely low concentrations without any contact with the sample; discriminate between and within multiple well-known Scotch whisky brands, and detect methanol concentrations well below the maximum human tolerable level.

  19. Sorção-dessorção do fungicida clorotalonil em solos com diferentes teores de matéria orgânica

    Directory of Open Access Journals (Sweden)

    J. B. Regitano

    2002-03-01

    Full Text Available A cinética e a sorção de pesticidas em solos permitem predizer a velocidade com que esta reação atinge o equilíbrio e investigar os possíveis mecanismos envolvidos durante a reação. Portanto, esses processos são fundamentais para que se possa compreender o destino dos pesticidas no solo. Este trabalho teve por objetivo estudar a sorção e a cinética do fungicida clorotalonil em cinco solos com diferentes teores de matéria orgânica do estado de São Paulo: Neossolo Quartzarênico órtico (RQo, Latossolo Vermelho distroférrico (LVdf-1 e LVdf-2, Latossolo Vermelho perférrico (LVj e Gleissolo (G. Nestes estudos, foi utilizado traçador radioativo, ou seja, 14C-clorotalonil, e a radioatividade foi detectada por espectrometria de cintilação líquida. Os ensaios foram realizados em sala climatizada (25±2ºC, em ambiente escuro. O ensaio de cinética constou de oito períodos de equilíbrio: 0; 0,5; 1,0; 2,0; 4,0; 8,0; 12,0 e 24,0h; sendo que nas amostras que atingiram equilíbrio (24h foram realizados os testes de dessorção, em quatro etapas subseqüentes. Nos estudos de isotermas de sorção, as concentrações de clorotalonil empregadas situaram-se entre 0,05 e 0,76µgmL-1. O modelo matemático de Elovich foi ajustado aos resultados do estudo de cinética e o modelo de Freundlich foi ajustado aos resultados do estudo de isoterma de sorção. Observou-se elevada sorção de clorotalonil nos solos estudados, exceto no solo arenoso com baixo teor de matéria orgânica (RQo. A sorção do clorotalonil relacionou-se positivamente com a matéria orgânica do solo. A cinética de sorção desse fungicida envolveu duas fases, uma imediata, de maior relevância quantitativa, e outra mais lenta. Esses resultados mostram que uma pequena fração do clorotalonil aplicado ao solo estaria disponível para ser lixiviado ao lençol freático, mas atenção especial é necessária quando ele é aplicado em solos arenosos com baixo teor de mat

  20. Isotermas de sorção de metais pesados em solos do cerrado de Goiás Sorption isotherm of heavy metals in soils of 'Cerrado' of Goiás

    Directory of Open Access Journals (Sweden)

    Luiz F. C. Oliveira

    2010-07-01

    Full Text Available A contaminação do solo e das águas subterrâneas por metais pesados é, extremamente perniciosa por serem basntante persistentes no ambiente. Objetivou-se, com este trabalho, a análise da sorção do Cu, Cr, Zn, Cd, Pb e Ni em Latossolo Vermelho Acriférrico (LVwf, Argissolo Vermelho Eutrófico (PVe, Nitossolo Vermelho Eutroférrico (NVef e Neossolo Quartzarênico (RQ pelos modelos potencial e linear da isoterma Freundlich. Para o estabelecimento de isotermas de sorção adicionaram-se a 5,0 mL de solo e 50,0 mL de solução contendo o metal pesado a ser avaliado com diferentes concentrações, respeitando-se os limites aceitáveis. As isotermas de sorção potencial e linear apresentaram bom ajuste para descrever o comportamento de adsorção dos metais pesados nas diferentes classes de solo estudadas. A sequência da retenção dos metais pesados em ordem decrescente, foi, para: o PVe: Cr+3 > Cr+6 > Ni+2 > Zn+2 > Cu+2 > Pb+2 > Cd+2; o LVwf: Cr+3 > Cr+6 > Ni+2 > Cu+2 > Cd+2 > Zn+2 > Pb+2; o RQ: Cr+6 > Cr+3 >Cu+2 > Pb+2 > Ni+2 > Zn+2 > Cd+2 e, para, o NVef: Cr+3 > Cr+6 > Pb+2 > Cu+2 > Zn+2 > Ni+2 >Cd+2. O RQ foi a classe de solo que apresentou menor retenção de metais em comparação com as demais classes de solo sendo, portanto, mais vulnerável à contaminação de águas subterrâneas.The contamination of soil and groundwater by heavy metals is extremely damaging due to high persistence of heavy metals in the environment. This work targeted the analysis of the sorption in Oxisol Typic Acrustox(LVwf, Ultisol (PVe, Kandic Oxisol (NVef and Quartzipsamment (RQ of heavy metals Cu, Cr, Zn, Cd, Pb and Ni. The sorption of the heavy metals in the soil was evaluated by batch method and described by potential and linear models of the Freundlich isotherm. For the establishment the of sorption isotherm, 50.0 mL of solution containing the heavy metal were added in 5.0 mL of soil, assessing with different concentrations within the acceptable soil

  1. Schiff base ligand

    Indian Academy of Sciences (India)

    Unknown

    Low-temperature stoichiometric Schiff base reaction in air in 3 : 1 mole ratio between benz- aldehyde and triethylenetetramine (trien) in methanol yields a novel tetraaza µ-bis(bidentate) acyclic ligand L. It was .... electrochemical work was performed as reported in ..... change in ligand shape through change in oxidation.

  2. Ligand modeling and design

    Energy Technology Data Exchange (ETDEWEB)

    Hay, B.P. [Pacific Northwest National Lab., Richland, WA (United States)

    1997-10-01

    The purpose of this work is to develop and implement a molecular design basis for selecting organic ligands that would be used in the cost-effective removal of specific radionuclides from nuclear waste streams. Organic ligands with metal ion specificity are critical components in the development of solvent extraction and ion exchange processes that are highly selective for targeted radionuclides. The traditional approach to the development of such ligands involves lengthy programs of organic synthesis and testing, which in the absence of reliable methods for screening compounds before synthesis, results in wasted research effort. The author`s approach breaks down and simplifies this costly process with the aid of computer-based molecular modeling techniques. Commercial software for organic molecular modeling is being configured to examine the interactions between organic ligands and metal ions, yielding an inexpensive, commercially or readily available computational tool that can be used to predict the structures and energies of ligand-metal complexes. Users will be able to correlate the large body of existing experimental data on structure, solution binding affinity, and metal ion selectivity to develop structural design criteria. These criteria will provide a basis for selecting ligands that can be implemented in separations technologies through collaboration with other DOE national laboratories and private industry. The initial focus will be to select ether-based ligands that can be applied to the recovery and concentration of the alkali and alkaline earth metal ions including cesium, strontium, and radium.

  3. The utilization of BSA-modified chip on the investigation of ligand ...

    African Journals Online (AJOL)

    Administrator

    2009-12-15

    Dec 15, 2009 ... investigation of ligand/protein interaction with surface plasma resonance ... for immobilizing proteins or low-molecular-weight ligands to dextran ..... contamination in dynamic aqueous environments using optical sensors. Anal.

  4. [Mucormycosis: Study of five cases found in San Juan de Dios hospital and Sor Maria Ludovica hospital in La Plata, Argentina].

    Science.gov (United States)

    Featherston, P L; Fernández, G; Munguía, H; Marín, M E

    1998-01-01

    Hospital San Juan de Dios and Sor María Ludovica in La Plata, between 1980 and 1997. Mucormicosis is a frequently fatal, opportunistic fungal infection, that affects immunocompromised patients. The risk factors include diabetes mellitus, leukemia, lymphoma, burns, etc. We present three cases of cutaneous mucormicosis in children 3, 10 and 11 years old, who had been sent to the hospital due to compound fractures in a car crash; one case of pulmonary mucormicosis in an adult 28 years old with prolonged corticotherapy and rhinocerebral mucormicosis in a patient 38 years old with a diagnosis of acute lymphoid leukemia.

  5. La imagen es la esencia: dialéctica de lo visual y cultura precolombina en Sor Juana Inés de la Cruz

    Directory of Open Access Journals (Sweden)

    Andrea Pezzé

    2015-07-01

    Full Text Available One of most important features of Neobarrocco is its cultural relation with images. This article, basing itself on Michel Foucault’s analysis of Las Meninas and on the Bolívar Echeverría’s Ethos barroco , aims to analyze the relation between image, the object of the portrait and observer in the poetry of Sor Juana Inés de la Cruz. Our objective is to understand as text puts that relation into poetry without reducing itself to a simple caption.

  6. Área de Arte y Salud del Hospital de Niños Sor María Ludovica de La Plata

    OpenAIRE

    Iriart Urruty, Andrea

    2014-01-01

    El Hospital de Niños “Sor María Ludovica” de la ciudad de La Plata, a partir de la firma de la disposición N° 940/13 por parte de la dirección del mismo, funciona el “Área de Arte y Salud” integrada por el Servicio Social, el Servicio de Salud Mental del Hospital, la Biblioteca Ambulante, el Taller de Plástica y Literatura y el Laboratorio de Arte que desarrolla el Grupo La Grieta. Esta área es un espacio institucional abocado a aunar criterios y conjugar inquietudes en torno al papel del ...

  7. Environment

    International Nuclear Information System (INIS)

    McIntyre, A.D.; Turnbull, R.G.H.

    1992-01-01

    The development of the hydrocarbon resources of the North Sea has resulted in both offshore and onshore environmental repercussions, involving the existing physical attributes of the sea and seabed, the coastline and adjoining land. The social and economic repercussions of the industry were equally widespread. The dramatic and speedy impact of the exploration and exploitation of the northern North Sea resources in the early 1970s, on the physical resources of Scotland was quickly realised together with the concern that any environmental and social damage to the physical and social fabric should be kept to a minimum. To this end, a wide range of research and other activities by central and local government, and other interested agencies was undertaken to extend existing knowledge on the marine and terrestrial environments that might be affected by the oil and gas industry. The outcome of these activities is summarized in this paper. The topics covered include a survey of the marine ecosystems of the North Sea, the fishing industry, the impact of oil pollution on seabirds and fish stocks, the ecology of the Scottish coastline and the impact of the petroleum industry on a selection of particular sites. (author)

  8. Glutamate receptor ligands

    DEFF Research Database (Denmark)

    Guldbrandt, Mette; Johansen, Tommy N; Frydenvang, Karla Andrea

    2002-01-01

    Homologation and substitution on the carbon backbone of (S)-glutamic acid [(S)-Glu, 1], as well as absolute stereochemistry, are structural parameters of key importance for the pharmacological profile of (S)-Glu receptor ligands. We describe a series of methyl-substituted 2-aminoadipic acid (AA...

  9. Omega-3 fatty acid docosahexaenoic acid increases SorLA/LR11, a sorting protein with reduced expression in sporadic Alzheimer's disease (AD): relevance to AD prevention.

    Science.gov (United States)

    Ma, Qiu-Lan; Teter, Bruce; Ubeda, Oliver J; Morihara, Takashi; Dhoot, Dilsher; Nyby, Michael D; Tuck, Michael L; Frautschy, Sally A; Cole, Greg M

    2007-12-26

    Environmental and genetic factors, notably ApoE4, contribute to the etiology of late-onset Alzheimer's disease (LOAD). Reduced mRNA and protein for an apolipoprotein E (ApoE) receptor family member, SorLA (LR11) has been found in LOAD but not early-onset AD, suggesting that LR11 loss is not secondary to pathology. LR11 is a neuronal sorting protein that reduces amyloid precursor protein (APP) trafficking to secretases that generate beta-amyloid (Abeta). Genetic polymorphisms that reduce LR11 expression are associated with increased AD risk. However these polymorphisms account for only a fraction of cases with LR11 deficits, suggesting involvement of environmental factors. Because lipoprotein receptors are typically lipid-regulated, we postulated that LR11 is regulated by docosahexaenoic acid (DHA), an essential omega-3 fatty acid related to reduced AD risk and reduced Abeta accumulation. In this study, we report that DHA significantly increases LR11 in multiple systems, including primary rat neurons, aged non-Tg mice and an aged DHA-depleted APPsw AD mouse model. DHA also increased LR11 in a human neuronal line. In vivo elevation of LR11 was also observed with dietary fish oil in young rats with insulin resistance, a model for type II diabetes, another AD risk factor. These data argue that DHA induction of LR11 does not require DHA-depleting diets and is not age dependent. Because reduced LR11 is known to increase Abeta production and may be a significant genetic cause of LOAD, our results indicate that DHA increases in SorLA/LR11 levels may play an important role in preventing LOAD.

  10. AMPA receptor ligands

    DEFF Research Database (Denmark)

    Strømgaard, Kristian; Mellor, Ian

    2004-01-01

    Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player in the f......Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player...... in the formation of memory. Hence, ligands affecting AMPARs are highly important for the study of the structure and function of this receptor, and in this regard polyamine-based ligands, particularly polyamine toxins, are unique as they selectively block Ca2+ -permeable AMPARs. Indeed, endogenous intracellular...

  11. Radiobiology with DNA ligands

    International Nuclear Information System (INIS)

    Weinreich, R.; Argentini, M.; Guenther, I.; Koziorowski, J.; Larsson, B.; Nievergelt-Egido, M.C.; Salt, C.; Wyer, L.; Dos Santos, D.F.; Hansen, H.J.

    1997-01-01

    The paper deals with the following topics: labelling of DNA ligands and other tumour-affinic compounds with 4.15-d 124 I, radiotoxicity of Hoechst 33258 and 33342 and of iodinated Hoechst 33258 in cell cultures, preparation of 76 Br-, 123 I-, and 221 At-labelled 5-halo-2'-deoxyuridine, chemical syntheses of boron derivatives of Hoechst 33258.III., Gadolinium neutron capture therapy

  12. Sorção do herbicida acetochlor em amostras de solo, ácidos húmicos e huminas de argissolo submetido à semeadura direta e ao preparo convencional Sorption of acetochlor herbicide by soil samples, humic acids and humin from an argisol under no-till and conventional tillage systems

    Directory of Open Access Journals (Sweden)

    Miguel Vicente Weiss Ferri

    2005-10-01

    Full Text Available A sorção de herbicidas no solo é um dos processos determinantes na sua dinâmica no ambiente. Para compostos fracamente polares, como é caso do acetochlor, a matéria orgânica do solo constitui o principal sorvente. O objetivo deste estudo foi avaliar a sorção de acetochlor em amostras de solo, de ácidos húmicos e de huminas de um Argissolo Vermelho distrófico (PVd submetido à semeadura direta e ao preparo convencional. Isotermas de sorção foram obtidas em temperatura ambiente e a concentração do herbicida foi determinada por cromatografia líquida de alta eficiência. As amostras de solo foram caracterizadas pelos teores de C orgânico e de substâncias húmicas; os ácidos húmicos e huminas foram caracterizados por análise elementar. A capacidade de sorção de acetochlor foi superior no solo de semeadura direta (Kd = 1,22 ± 0,11 L kg-1, K OC = 116 ± 10 L kg-1 C em relação ao preparo convencional (Kd = 0,76 ± 0,08 L kg-1, K OC = 86 ± 8 L kg-1 C. Este comportamento foi relacionado, em parte, com o maior teor de C no solo tratado com semeadura direta. Nos ácidos húmicos de preparo convencional, a sorção (Kd = 178 ± 18,9 L kg-1, K OC = 352 ± 37 L kg-1C foi similar à verificada nos ácidos húmicos de semeadura direta (Kd = 158 ± 14,6 L kg-1, K OC = 321 ± 30 L kg-1 C; situação semelhante foi observada com as huminas. Dentre as frações húmicas avaliadas, as huminas apresentaram maior capacidade de sorção (Kd = 1.028 e 1.183 L kg-1, K OC = 2.691 e 2.892 L kg-1 C.The sorption of herbicides to soil is a process determinant of its dynamics in the environment. For weakly polar compounds such as acetochlor, organic matter represents the main sorbent in soil. The goal of this study was to evaluate the sorption of acetochlor on soil samples, humic acids and humin from an "Argissolo Vermelho distrófico" (PVd-Paleudult under no-till and conventional tillage systems. Sorption isotherms were carried out at room

  13. Ligand Exchange Kinetics of Environmentally Relevant Metals

    Energy Technology Data Exchange (ETDEWEB)

    Panasci, Adele Frances [Univ. of California, Davis, CA (United States)

    2014-07-15

    The interactions of ground water with minerals and contaminants are of broad interest for geochemists but are not well understood. Experiments on the molecular scale can determine reaction parameters (i.e. rates of ligand exchange, activation entropy, activation entropy, and activation volume) that can be used in computations to gain insight into reactions that occur in natural groundwaters. Experiments to determine the rate of isotopic ligand exchange for three environmentally relevant metals, rhodium (Rh), iron (Fe), and neptunium (Np), are described. Many environmental transformations of metals (e.g. reduction) in soil occur at trivalent centers, Fe(III) in particular. Contaminant ions absorb to mineral surfaces via ligand exchange, and the reversal of this reaction can be dangerous, releasing contaminants into the environment. Ferric iron is difficult to study spectroscopically because most of its complexes are paramagnetic and are generally reactive toward ligand exchange; therefore, Rh(III), which is diamagnetic and less reactive, was used to study substitution reactions that are analogous to those that occur on mineral oxide surfaces. Studies on both Np(V) and Np(VI) are important in their own right, as 237Np is a radioactive transuranic element with a half-life of 2 million years.

  14. Bexarotene ligand pharmaceuticals.

    Science.gov (United States)

    Hurst, R E

    2000-12-01

    Bexarotene (LGD-1069), from Ligand, was the first retinoid X receptor (RXR)-selective, antitumor retinoid to enter clinical trials. The company launched the drug for the treatment of cutaneous T-cell lymphoma (CTCL), as Targretin capsules, in the US in January 2000 [359023]. The company filed an NDA for Targretin capsules in June 1999, and for topical gel in December 1999 [329011], [349982] specifically for once-daily oral administration for the treatment of patients with early-stage CTCL who have not tolerated other therapies, patients with refractory or persistent early stage CTCL and patients with refractory advanced stage CTCL. The FDA approved Targretin capsules at the end of December 1999 for once-daily oral treatment of all stages of CTCL in patients refractory to at least one prior systemic therapy, at an initial dose of 300 mg/m2/day. After an NDA was submitted in December 1999 for Targretin gel, the drug received Priority Review status for use as a treatment of cutaneous lesions in patients with stage IA, IB or IIA CTCL [354836]. The FDA issued an approvable letter in June 2000, and granted marketing clearance for CTCL in the same month [370687], [372768], [372769], [373279]. Ligand had received Orphan Drug designation for this indication [329011]. At the request of the FDA, Ligand agreed to carry out certain post-approval phase IV and pharmacokinetic studies [351604]. The company filed an MAA with the EMEA for Targretin Capsules to treat lymphoma in November 1999 [348944]. The NDA for Targretin gel is based on a multicenter phase III trial that was conducted in the US, Canada, Europe and Australia involving 50 patients and a multicenter phase I/II clinical program involving 67 patients. Targretin gel was evaluated for the treatment of patients with early stage CTCL (IA-IIA) who were refractory to, intolerant to, or reached a response plateau for at least 6 months on at least two prior therapies. Efficacy results exceeded the protocol-defined response

  15. Benzannulated Tris(2-mercapto-1-imidazolyl)hydroborato Ligands: Tetradentate κ4–S3H Binding and Access to Monomeric Monovalent Thallium in an [S3] Coordination Environment

    Science.gov (United States)

    Rong, Yi; Palmer, Joshua H.; Parkin, Gerard

    2013-01-01

    The benzannulated tris(mercaptoimidazolyl)borohydride sodium complex, [TmButBenz]Na, has been synthesized via the reaction of NaBH4 with 1-tert-butyl-1,3-dihydro-2H-benzimidazole-2-thione, while [TmMeBenz]K has been synthesized via the reaction of KBH4 with 1-methyl-1,3-dihydro-2H-benzimidazole-2-thione. The molecular structures of the solvated adducts, {[TmButBenz]Na(THF)}2(μ-THF)2 and [TmMeBenz]K(OCMe2)3, have been determined by X-ray diffraction, which demonstrates that the [TmR] ligands in these complexes adopt different coordination modes to that in {[TmMeBenz]Na}2(μ-THF)3. Specifically, while the [TmMeBenz] ligand of the sodium complex {[TmMeBenz]Na}2(μ-THF)3 adopts a κ3-S3 coordination mode, the potassium complex [TmMeBenz]K(OCMe2)3 adopts a most uncommon inverted κ4-S3H coordination mode in which the potassium binds to all three sulfur donors and the hydrogen of the B–H group in a linear K•••H–B manner. Furthermore, the [TmButBenz] ligand of {[TmButBenz]Na(THF)}2(μ-THF)2 adopts a κ3-S2H coordination mode, thereby demonstrating the flexibility of this ligand system. The monovalent thallium compounds, [TmMeBenz]Tl and [TmButBenz]Tl, have been obtained via the corresponding reactions of [TmMeBenz]Na and [TmButBenz]Na with TlOAc. X-ray diffraction demonstrates that the three sulfur donors of the [TmRBenz] ligands of both [TmMeBenz]Tl and [TmButBenz]Tl chelate to thallium. This coordination mode is in marked contrast to that in other [TmR]Tl compounds, which exist as dinuclear molecules wherein two of the sulfur donors coordinate to different thallium centers. As such, this observation provides further evidence that benzannulation promotes κ3-S3 coordination in this system. PMID:24201311

  16. Sorção e dessorção do ametryn em Latossolos brasileiros Sorption and desorption of ametryn in Brazilian Latosols

    Directory of Open Access Journals (Sweden)

    L.O.C. Silva

    2012-09-01

    Full Text Available O conhecimento dos processos de retenção de herbicidas em solo é fundamental para se prever o potencial de lixiviação e degradação e a eficiência no controle das plantas daninhas. Objetivou-se com este trabalho avaliar os processos de sorção e dessorção do ametryn em quatro solos brasileiros: Latossolo Vermelho-Amarelo (LVA, Latossolo Vermelho-Amarelo húmico (LVAh, Latossolo Vermelho (LV e Latossolo Amarelo (LA, com diferentes valores de pH. Para isso, utilizou-se o método Batch Equilibrium em condições controladas de laboratório e análise por cromatografia líquida de alta eficiência, com detector UV-Vis a 245 nm. Considerando os valores da constante de Freundlich modificada (K'f, verificou-se, entre os solos estudados, a ordem crescente de sorção do ametryn: LV pH 6,06 Knowledge of herbicide retention processes in soil is fundamental to predict leaching potential, degradation, and weed control efficiency. The objective of this study was to evaluate the processes of sorption and desorption of ametryn in four Brazilian soils: Red-Yellow Latosol (LVA, Red-Yellow humic Latosol (LVAh, Red Latosol (LV, and Yellow Latosol (LA, with different pH values. Thus, the method "Batch Equilibrium" was applied under controlled laboratory conditions, and analysis by high performance liquid chromatography using UV-Vis detector at 245 nm. Considering the values of the modified Freundlich constant (K'f, the following increasing sorption order of ametryn was verified: LV pH 6.06 <5.00 LV pH <6.30 LA pH <6.11 pH LVA

  17. Coordination chemistry of two heavy metals: I, Ligand preferences in lead(II) complexation, toward the development of therapeutic agents for lead poisoning: II, Plutonium solubility and speciation relevant to the environment

    Energy Technology Data Exchange (ETDEWEB)

    Neu, Mary Patricia [Univ. of California, Berkeley, CA (United States)

    1993-11-01

    The coordination chemistry and solution behavior of the toxic ions lead(II) and plutonium(IV, V, VI) have been investigated. The ligand pKas and ligand-lead(II) stability constants of one hydroxamic acid and four thiohydroaxamic acids were determined. Solution thermodynamic results indicate that thiohydroxamic acids are more acidic and slightly better lead chelators than hydroxamates, e.g., N-methylthioaceto-hydroxamic acid, pKa = 5.94, logβ120 = 10.92; acetohydroxamic acid, pKa = 9.34, logβ120 = 9.52. The syntheses of lead complexes of two bulky hydroxamate ligands are presented. The X-ray crystal structures show the lead hydroxamates are di-bridged dimers with irregular five-coordinate geometry about the metal atom and a stereochemically active lone pair of electrons. Molecular orbital calculations of a lead hydroxamate and a highly symmetric pseudo octahedral lead complex were performed. The thermodynamic stability of plutonium(IV) complexes of the siderophore, desferrioxamine B (DFO), and two octadentate derivatives of DFO were investigated using competition spectrophotometric titrations. The stability constant measured for the plutonium(IV) complex of DFO-methylterephthalamide is logβ120 = 41.7. The solubility limited speciation of 242Pu as a function of time in near neutral carbonate solution was measured. Individual solutions of plutonium in a single oxidation state were added to individual solutions at pH = 6.0, T = 30.0, 1.93 mM dissolved carbonate, and sampled over intervals up to 150 days. Plutonium solubility was measured, and speciation was investigated using laser photoacoustic spectroscopy and chemical methods.

  18. Coordination chemistry of two heavy metals: I, Ligand preferences in lead(II) complexation, toward the development of therapeutic agents for lead poisoning: II, Plutonium solubility and speciation relevant to the environment

    International Nuclear Information System (INIS)

    Neu, M.P.

    1993-11-01

    The coordination chemistry and solution behavior of the toxic ions lead(II) and plutonium(IV, V, VI) have been investigated. The ligand pK a s and ligand-lead(II) stability constants of one hydroxamic acid and four thiohydroaxamic acids were determined. Solution thermodynamic results indicate that thiohydroxamic acids are more acidic and slightly better lead chelators than hydroxamates, e.g., N-methylthioaceto-hydroxamic acid, pK a = 5.94, logβ 120 = 10.92; acetohydroxamic acid, pK a = 9.34, logβ l20 = 9.52. The syntheses of lead complexes of two bulky hydroxamate ligands are presented. The X-ray crystal structures show the lead hydroxamates are di-bridged dimers with irregular five-coordinate geometry about the metal atom and a stereochemically active lone pair of electrons. Molecular orbital calculations of a lead hydroxamate and a highly symmetric pseudo octahedral lead complex were performed. The thermodynamic stability of plutonium(IV) complexes of the siderophore, desferrioxamine B (DFO), and two octadentate derivatives of DFO were investigated using competition spectrophotometric titrations. The stability constant measured for the plutonium(IV) complex of DFO-methylterephthalamide is logβ 110 = 41.7. The solubility limited speciation of 242 Pu as a function of time in near neutral carbonate solution was measured. Individual solutions of plutonium in a single oxidation state were added to individual solutions at pH = 6.0, T = 30.0, 1.93 mM dissolved carbonate, and sampled over intervals up to 150 days. Plutonium solubility was measured, and speciation was investigated using laser photoacoustic spectroscopy and chemical methods

  19. Influência da matéria orgânica na sorção e dessorção do glifosato em solos com diferentes atributos mineralógicos

    Directory of Open Access Journals (Sweden)

    F. Prata

    2000-12-01

    Full Text Available O presente trabalho objetivou estudar a influência da matéria orgânica na sorção e dessorção do glifosato em três solos com diferentes atributos mineralógicos. Os ensaios foram realizados no Laboratório de Ecotoxicologia do Centro de Energia Nuclear na Agricultura (CENA/USP, em Piracicaba (SP. Os solos foram classificados como: Nitossolo Vermelho Eutroférrico (NVef, Latossolo Amarelo Ácrico (LAw e Gleissolo (G. Para avaliar a influência da matéria orgânica na sorção do glifosato, os solos foram oxidados com H2O2 (30%. O delineamento experimental foi inteiramente casualizado, com arranjo fatorial 3 x 2. No estudo da sorção, foram utilizadas cinco concentrações do herbicida: 0,42; 0,84; 1,68; 3,36 e 6,72 mg L-1, com radioatividade de 0,233 kBq mL-1. Os estudos de dessorção foram realizados na concentração de 0,84 mg L-1. Os resultados mostraram que o glifosato foi extremamente sorvido aos solos, independentemente da presença da matéria orgânica. A sorção do glifosato relacionou-se principalmente com a fração mineral dos solos, isto é, com os óxidos de Fe e Al, tendo a fração orgânica desempenhado papel secundário. Não houve dessorção do glifosato, ficando a maior parte como resíduo ligado.

  20. Ligand Depot: a data warehouse for ligands bound to macromolecules.

    Science.gov (United States)

    Feng, Zukang; Chen, Li; Maddula, Himabindu; Akcan, Ozgur; Oughtred, Rose; Berman, Helen M; Westbrook, John

    2004-09-01

    Ligand Depot is an integrated data resource for finding information about small molecules bound to proteins and nucleic acids. The initial release (version 1.0, November, 2003) focuses on providing chemical and structural information for small molecules found as part of the structures deposited in the Protein Data Bank. Ligand Depot accepts keyword-based queries and also provides a graphical interface for performing chemical substructure searches. A wide variety of web resources that contain information on small molecules may also be accessed through Ligand Depot. Ligand Depot is available at http://ligand-depot.rutgers.edu/. Version 1.0 supports multiple operating systems including Windows, Unix, Linux and the Macintosh operating system. The current drawing tool works in Internet Explorer, Netscape and Mozilla on Windows, Unix and Linux.

  1. Metal-ligand interactions

    Science.gov (United States)

    Ervin, Kent M.

    Experimental studies of the interactions of small transition-metal cluster anions with carbonyl ligands are reviewed and compared with neutral and cationic clusters. Under thermal conditions, the reaction rates of transition-metal clusters with carbon monoxide are measured as a function of cluster size. Saturation limits for carbon monoxide addition can be related to the geometric structures of the clusters. Both energy-resolved threshold collision-induced dissociation experiments and time-resolved photodissociation experiments are used to measure metal-carbonyl binding energies. For platinum and palladium trimer anions, the carbonyl binding energies are assigned to different geometric binding sites. Platinum and palladium cluster anions catalyse the oxidation of carbon monoxide to carbon dioxide in a full catalytic cycle at thermal energies.

  2. Melatonin: functions and ligands.

    Science.gov (United States)

    Singh, Mahaveer; Jadhav, Hemant R

    2014-09-01

    Melatonin is a chronobiotic substance that acts as synchronizer by stabilizing bodily rhythms. Its synthesis occurs in various locations throughout the body, including the pineal gland, skin, lymphocytes and gastrointestinal tract (GIT). Its synthesis and secretion is controlled by light and dark conditions, whereby light decreases and darkness increases its production. Thus, melatonin is also known as the 'hormone of darkness'. Melatonin and analogs that bind to the melatonin receptors are important because of their role in the management of depression, insomnia, epilepsy, Alzheimer's disease (AD), diabetes, obesity, alopecia, migraine, cancer, and immune and cardiac disorders. In this review, we discuss the mechanism of action of melatonin in these disorders, which could aid in the design of novel melatonin receptor ligands. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Macrocyclic G-quadruplex ligands

    DEFF Research Database (Denmark)

    Nielsen, M C; Ulven, Trond

    2010-01-01

    are macrocyclic structures which have been modeled after the natural product telomestatin or from porphyrin-based ligands discovered in the late 1990s. These two structural classes of G-quadruplex ligands are reviewed here with special attention to selectivity and structure-activity relationships, and with focus...

  4. INTERROGACIÓN Y ARGUMENTACIÓN EN LA CARTA ATENAGÓRICA DE SOR JUANA INÉS DE LA CRUZ

    Directory of Open Access Journals (Sweden)

    Márlom Fermín Pérez Villegas

    2017-01-01

    Full Text Available Los estudios argumentativos de la Carta Atenagórica revelan que existe un vacío en el análisis de ciertas estrategias, como los enunciados interrogativos. Este trabajo, a través del modelo de Toulmin, explora la función de aquellos desde una perspectiva pragmática, para conocer su intención e impacto argumentativo en el texto. Pero el análisis de la estructura identifica también el estilo retórico que Sor Juana Inés de la Cruz usó para responder a sus oponentes, además de su derecho como persona, mujer y religiosa para hablar y sostener su tesis, es decir, de ser un interlocutor del discurso de la época. De esta forma, los interrogativos son otra faceta de la forma estilística que la Décima Musa usó para la creación de su defensa discursiva.

  5. La reinvención de la melancolía: “Primero sueño” de Sor Juana y Melancholia I de Durero

    Directory of Open Access Journals (Sweden)

    Robin Ann Rice Carlssohn

    2015-07-01

    Full Text Available Hasta el siglo XV, la medicina natural consideraba la melancolía cómo una enfermedad lamentable que afectaba la moralidad y el ser físico del hombre. Bajo las influencias del pensamiento neoplatónico florentino, el melancólico surgió como prototipo del genio artístico moderno. Tanto Durero, que produjo su Melancholia 1 en 1514, como Sor Juana Inés de la Cruz, que redactó el “Primer sueño” por 1685, fueron fuertemente influenciados por el humanismo italiano. La hipótesis del trabajo es que el “Primer sueño” es una ecfrasis de Melancholia 1y que las dos obras son un parteaguas por el cambio de la percepción de la melancolía. Bajo el influjo del pensamiento de Ficino, entre otros, la melancolía se convirtió en signo del genio y su deseo de desamarrarse del terreno físico para ascender a la contemplación divina.

  6. Two novel mixed-ligand complexes containing organosulfonate ligands.

    Science.gov (United States)

    Li, Mingtian; Huang, Jun; Zhou, Xuan; Fang, Hua; Ding, Liyun

    2008-07-01

    The structures reported herein, viz. bis(4-aminonaphthalene-1-sulfonato-kappaO)bis(4,5-diazafluoren-9-one-kappa(2)N,N')copper(II), [Cu(C(10)H(8)NO(3)S)(2)(C(11)H(6)N(2)O)(2)], (I), and poly[[[diaquacadmium(II)]-bis(mu-4-aminonaphthalene-1-sulfonato)-kappa(2)O:N;kappa(2)N:O] dihydrate], {[Cd(C(10)H(8)NO(3)S)(2)(H(2)O)(2)].2H(2)O}(n), (II), are rare examples of sulfonate-containing complexes where the anion does not fulfill a passive charge-balancing role, but takes an active part in coordination as a monodentate and/or bridging ligand. Monomeric complex (I) possesses a crystallographic inversion center at the Cu(II) atom, and the asymmetric unit contains one-half of a Cu atom, one complete 4-aminonaphthalene-1-sulfonate (ans) ligand and one 4,5-diazafluoren-9-one (DAFO) ligand. The Cu(II) atom has an elongated distorted octahedral coordination geometry formed by two O atoms from two monodentate ans ligands and by four N atoms from two DAFO molecules. Complex (II) is polymeric and its crystal structure is built up by one-dimensional chains and solvent water molecules. Here also the cation (a Cd(II) atom) lies on a crystallographic inversion center and adopts a slightly distorted octahedral geometry. Each ans anion serves as a bridging ligand linking two Cd(II) atoms into one-dimensional infinite chains along the [010] direction, with each Cd(II) center coordinated by four ans ligands via O and N atoms and by two aqua ligands. In both structures, there are significant pi-pi stacking interactions between adjacent ligands and hydrogen bonds contribute to the formation of two- and three-dimensional networks.

  7. Correcting ligands, metabolites, and pathways

    NARCIS (Netherlands)

    Ott, M.A.; Vriend, G.

    2006-01-01

    BACKGROUND: A wide range of research areas in bioinformatics, molecular biology and medicinal chemistry require precise chemical structure information about molecules and reactions, e.g. drug design, ligand docking, metabolic network reconstruction, and systems biology. Most available databases,

  8. Standards, options and recommendations: concomitant radio chemotherapy for cancer of the cervix: a critical analysis of the literature and update of SOR

    International Nuclear Information System (INIS)

    Haie-Meder, C.; Lhomme, C.; Fervers, B.; Bataillard, A.; Chauvergne, J.; Fondrinier, E.; Guastalla, J.P.; Resbeut, M.

    2000-01-01

    The 'Standards, Options and Recommendations'(SOR) project, started in 1993, is a collaboration between the National Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres (CRLCC) and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. To update, according to the methodology of SOR, the Standards, Options and Recommendations for the management of patients with cancer of the cervix, and in particular, the place of concomitant radio-chemotherapy. Data have been identified by a literature search using Medline (to April 1999) and the personal reference lists of experts. Once the guidelines were defined, the document was submitted for review to independent national and international reviewers and to the medical committees of the CRCC. The principle recommendations concerning the place of radio-chemotherapy in the treatment of cancer of the cervix are 1) the available data shows a significant increase in local control (level of evidence A) and of overall survival (level of evidence B1)following concomitant radio-chemotherapy as compared to radiotherapy alone or the combination of radiotherapy-hydroxyurea. For stages IB, IIA, proximal IIB with bad prognostic factors (tumour size greater than 4 cm and/or invasion of pelvic nodes and/or microscopic invasion of the parametrium) and without lumbo-aortic nodal invasion, concomitant radio-chemotherapy can be considered as standard treatment. This benefit is less clear for stages distal IIB, III and IVA without para-aortic nodal invasion (level of evidence C) and must be confirmed (expert agreement). 2) the toxicity of radio-chemotherapy is essentially hematologic and

  9. Interaction of In(I) and Tl(I) cations with 2,6-diaryl pyridine ligands: cation encapsulation within a very weakly interacting N/arene host environment.

    Science.gov (United States)

    Mansaray, Hassanatu B; Tang, Christina Y; Vidovic, Dragoslav; Thompson, Amber L; Aldridge, Simon

    2012-12-03

    The interaction of 2,6-dimesitylpyridine with Tl(I) and In(I) cations has been investigated with a view to developing tractable molecular M(I) compounds which are soluble in organic media. In stark contrast to isosteric and isoelectronic terphenyl systems, complexes featuring the [(2,6-Mes(2)py)M](+) fragment feature very weak metal-ligand interactions in the solid state, as revealed by M-N distances of the order of 2.45 Å (M = In) and 2.64 Å (M = Tl). While additional weak π interactions are observed with arene solvate molecules in these systems, the related 2:1 complex [(2,6-Mes(2)py)(2)In][BAr(f)(4)] features an In(I) center wholly encapsulated by the bulky Mes(2)py donors, and even longer In-N distances [2.586(6) and 2.662(5) Å]. These contacts are about 0.5 Å greater than the sum of the respective covalent radii (2.13 Å) and provide evidence for an effectively "naked" In(I) cation stabilized to a minor extent by orbital interactions.

  10. Influência da polaridade de pesticidas não-iônicos sobre sua sorção em um latossolo Influence of the polarity of non-ionic pesticides on their sorption by a latosoil

    Directory of Open Access Journals (Sweden)

    Lenin Piasarolo

    2008-12-01

    Full Text Available Investigou-se a influência da polaridade de pesticidas não-iônicos sobre sua sorção em material do horizonte A de um Latossolo Vermelho Acriférrico típico. Foram estudados treze pesticidas, abrangendo uma ampla faixa de polaridade, expressa na forma do coeficiente de partição do composto entre n-octanol e água (Kow. Foram obtidas as isotermas de sorção dos pesticidas, agitando-se subamostras do solo com soluções aquosas dos mesmos, sendo suas determinações quantitativas feitas por cromatografia líquida de alta eficiência. As isotermas de sorção dos pesticidas revelaram-se bem ajustadas ao modelo de Freundlich, com seus valores de coeficiente de sorção (Kf variando de 0,2 a 202 mL.nmol-1. Os valores de log Kf e de log Kow dos pesticidas mostraram-se linearmente correlacionados (R² = 0,87, indicando que a partição hidrofóbica na matéria orgânica foi o principal mecanismo de sorção dos compostos no solo. Para a maioria dos pesticidas, os valores de Kf obtidos foram maiores do que aqueles previstos pela equação de Briggs (1981, a qual relaciona o valor de Kf do pesticida com o seu valor de Kow e o teor de matéria orgânica do solo. Assim, os resultados mostraram que a referida equação, obtida em solos da Inglaterra, não é adequada para a previsão do valor de Kf de pesticidas no solo estudado, e que a natureza da matéria orgânica pode ser um importante fator a influenciar a sorção de pesticidas não-iônicos em solos.The sorption of thirteen non-ionic pesticides, with varying n-octanol/water partition coefficients (Kow, by soil material taken from the A horizon of an Acriferric Red Latosol was investigated. Sorption isotherms of the pesticides were determined by the shake flask method. The concentrations of the chemicals in aqueous solutions were measured by HPLC with UV detector. Sorption isotherms of all compounds fitted well the Freundlich model, with sorption coefficient (Kf values ranging from 0,2 to 202

  11. Avaliação em curto e médio prazo da sorção e da solubilidade de resinas compostas à base de metacrilato e de silorano em saliva artificial

    Directory of Open Access Journals (Sweden)

    Isabel Cristina Celerino de Moraes Porto

    Full Text Available INTRODUÇÃO: A absorção/adsorção de moléculas de água por monômeros hidrofílicos dentro de materiais resinosos expostos à umidade da boca pode resultar em degradação. OBJETIVO: Este estudo avaliou sorção e solubilidade de resinas compostas à base de metacrilato e silorano em contato com saliva artificial, nos períodos de um dia (curto prazo, e 30 e 90 dias (médio prazo. MATERIAL E MÉTODO: Sessenta corpos de prova foram confeccionados com as resinas Filtek® Z250 e Filtek® P90 Silorano (3M/ESPE, e depois imersos em saliva artificial a 37 ± 1 ºC durante um, 30 e 90 dias. Os dados foram analisados usando-se ANOVA um fator/dois fatores seguido dos testes Tukey ou Tamhane (α = 0,05. RESULTADO: As médias de sorção das duas resinas aumentaram com o tempo (p = 0,001. A sorção de Z250 (1 e 90 d foi significativamente maior do que de P90 (p = 0,008, com valores semelhantes após 30 dias. A solubilidade das resinas também aumentou com o tempo, com diferença significativa entre todos os períodos (p = 0,001, exceto para a resina P90 (entre 1 e 30 d. Não houve diferença estatística significante entre os grupos Z250 (1 d e P90 (1 dia, Z250 (1 d e P90 (30 d, e Z250 (30 d e P90 (90 d. Para os demais pares, comprovaram-se diferenças significativas (p < 0,001. CONCLUSÃO: As propriedades de sorção e solubilidade das resinas compostas testadas foram influenciadas pelo tempo de exposição à saliva artificial. O silorano teve desempenho ora melhor ora semelhante à resina de metacrilato.

  12. LigandRFs: random forest ensemble to identify ligand-binding residues from sequence information alone

    KAUST Repository

    Chen, Peng; Huang, Jianhua Z; Gao, Xin

    2014-01-01

    Protein-ligand binding is important for some proteins to perform their functions. Protein-ligand binding sites are the residues of proteins that physically bind to ligands. Despite of the recent advances in computational prediction

  13. MODELO DE FEMINIDAD DEL SIGLO XVII: CENSURA Y SEÑALAMIENTO. EL CASO DE SOR JUANA INÉS DE LA CRUZ

    Directory of Open Access Journals (Sweden)

    Karen Esmeralda Rivera López

    2015-06-01

    Full Text Available El siguiente trabajo estudia el modelo de mujer propio del siglo XVII en el contexto del llamado periodo de la Colonia en Hispanoamérica, específi camente en la Nueva España (México. En él se revela así la construcción social de la feminidad durante ese periodo, lo que permite posicionar dentro de la cuestión la obra de una de las mujeres más sobresalientes de dicho periodo, sor Juana Inés de la Cruz. Revisar los modelos y construcciones del deber ser femenino resulta trascendental si queremos entender el contexto social, cultural y político en el que se desenvolvió esta autora, que es una de las literatas y pensadoras de una época en la cual se negaba a las mujeres el derecho a educarse, y también por censurar y silenciarlas cuando transgredían el espacio público, principalmente masculino. AbstractThis paper focuses on the study of the woman model in seventeenth century in the context of the period called colonization time in Latin America, in New Spain (Mexico specifi cally. In this work, the social construction of femininity is revealed during this period, which has the intention to position the work of one of the most prominent woman of this period, sister Juana Ines de la Cruz. Reviewing the models and the constructions of being female is transcendental if we want to understand the social cultural and political context lived by this author; she is considered as a literate and thinkers from this time when the right to educate was denied to women, and to censor and silence them when they transgressed the public space, mainly male.

  14. Sorção de fósforo em função do teor inicial e de sistemas de manejo de solos

    Directory of Open Access Journals (Sweden)

    D. S. Rheinheimer

    2003-02-01

    Full Text Available A relação entre o P sorvido/P solução do solo pode ser influenciada pelo teor de P previamente sorvido e pelos sistemas de manejo. Este trabalho teve o objetivo de avaliar as modificações na capacidade de sorção máxima (Pmax e na constante relacionada com a energia de ligação de P com os colóides (k da isoterma de Langmuir, provocadas (a pela inclusão do teor de P previamente sorvido (Ppre e (b por sistemas de manejo de solos. Coletaram-se, em maio de 1997, amostras de solo (Latossolo Vermelho distroférrico típico, Latossolo Vermelho distrófico típico e Argissolo Vermelho distrófico típico, em três camadas (0-2,5, 2,5-7,5 e 7,5-17,5 cm, de três experimentos instalados a partir de 1979, envolvendo os sistemas plantio direto e cultivo convencional com diferentes sucessões de cultura. O solo foi equilibrado com oito concentrações de P em solução de CaCl2 0,001 mol L-1. Após a agitação por 16 h, avaliou-se a concentração de P no sobrenadante. Os dados de P-sorvido e P-solução foram ajustados à equação de Langmuir, obtendo-se a Pmax e a k, considerando ou não o Ppre. A inclusão do Ppre no modelo de Langmuir aumenta, em média, 2,9 vezes o valor da k e não afeta a Pmax, no LVdf, e aumenta em todas as camadas, no LVd, e na camada superficial, no PVd. A Pmax é pouco influenciada pelos métodos de preparo do solo, sucessões de culturas e camadas amostradas.

  15. Rosetta Ligand docking with flexible XML protocols.

    Science.gov (United States)

    Lemmon, Gordon; Meiler, Jens

    2012-01-01

    RosettaLigand is premiere software for predicting how a protein and a small molecule interact. Benchmark studies demonstrate that 70% of the top scoring RosettaLigand predicted interfaces are within 2Å RMSD from the crystal structure [1]. The latest release of Rosetta ligand software includes many new features, such as (1) docking of multiple ligands simultaneously, (2) representing ligands as fragments for greater flexibility, (3) redesign of the interface during docking, and (4) an XML script based interface that gives the user full control of the ligand docking protocol.

  16. The chemistry of separations ligand degradation by organic radical cations

    International Nuclear Information System (INIS)

    Mezyk, S.P.; Horne, G.P.; Mincher, B.J.; Zalupski, P.R.; Cook, A.R.; Wishart, J.F.

    2016-01-01

    Solvent based extractions of used nuclear fuel use designer ligands in an organic phase extracting ligand complexed metal ions from an acidic aqueous phase. These extractions will be performed in highly radioactive environments, and the radiation chemistry of all these complexing agents and their diluents will play a major role in determining extraction efficiency, separation factors, and solvent-recycle longevity. Although there has been considerable effort in investigating ligand damage occurring in acidic water radiolysis conditions, only minimal fundamental kinetic and mechanistic data has been reported for the degradation of extraction ligands in the organic phase. Extraction solvent phases typically use normal alkanes such as dodecane, TPH, and kerosene as diluents. The radiolysis of such diluents produce a mixture of radical cations (R"."+), carbon-centered radicals (R".), solvated electrons, and molecular products such as hydrogen. Typically, the radical species will preferentially react with the dissolved oxygen present to produce relatively inert peroxyl radicals. This isolates the alkane radical cation species, R"."+ as the major radiolytically-induced organic species that can react with, and degrade, extraction agents in this phase. Here we report on our recent studies of organic radical cation reactions with 2 ligands: CMPO and TODGA. Elucidating these parameters, and combining them with the known acidic aqueous phase chemistry, will allow a full, fundamental, understanding of the impact of radiation on solvent extraction based separation processes to be achieved. (authors)

  17. The chemistry of separations ligand degradation by organic radical cations

    Energy Technology Data Exchange (ETDEWEB)

    Mezyk, S.P.; Horne, G.P. [California State University at Long Beach, Long Beach, CA 90840 (United States); Mincher, B.J.; Zalupski, P.R. [Idaho National Laboratory, Idaho Falls, ID 83415 (United States); Cook, A.R.; Wishart, J.F. [Chemistry Department, Brookhaven National Laboratory, New York, 11973 (United States)

    2016-07-01

    Solvent based extractions of used nuclear fuel use designer ligands in an organic phase extracting ligand complexed metal ions from an acidic aqueous phase. These extractions will be performed in highly radioactive environments, and the radiation chemistry of all these complexing agents and their diluents will play a major role in determining extraction efficiency, separation factors, and solvent-recycle longevity. Although there has been considerable effort in investigating ligand damage occurring in acidic water radiolysis conditions, only minimal fundamental kinetic and mechanistic data has been reported for the degradation of extraction ligands in the organic phase. Extraction solvent phases typically use normal alkanes such as dodecane, TPH, and kerosene as diluents. The radiolysis of such diluents produce a mixture of radical cations (R{sup .+}), carbon-centered radicals (R{sup .}), solvated electrons, and molecular products such as hydrogen. Typically, the radical species will preferentially react with the dissolved oxygen present to produce relatively inert peroxyl radicals. This isolates the alkane radical cation species, R{sup .+} as the major radiolytically-induced organic species that can react with, and degrade, extraction agents in this phase. Here we report on our recent studies of organic radical cation reactions with 2 ligands: CMPO and TODGA. Elucidating these parameters, and combining them with the known acidic aqueous phase chemistry, will allow a full, fundamental, understanding of the impact of radiation on solvent extraction based separation processes to be achieved. (authors)

  18. Sorção e mobilidade do lítio em solos de áreas de disposição final de resíduos sólidos urbanos

    Directory of Open Access Journals (Sweden)

    Luiz Fernando Coutinho de Oliveira

    2013-06-01

    Full Text Available Um dos grandes problemas da atualidade é a disposição inadequada dos resíduos sólidos urbanos no solo, e seus efeitos recaem, principalmente, na contaminação das águas e do solo. Este trabalho objetivou o estudo da sorção e da mobilidade do Lítio nos solos das áreas de disposição de resíduos sólidos urbanos dos municípios de Lavras, Campo Belo e Pouso Alegre, MG. A partir dos ensaios de sorção em batelada e mobilidade do Li em colunas de solo, ajustaram-se os parâmetros das isotermas de Freundlich e da equação de transporte de solutos no solo. Pelos resultados obtidos verificou-se que, dentre os solos avaliados, o do município de Lavras foi o que apresentou a maior mobilidade do Li seguido dos solos de Pouso Alegre e Campo Belo, sendo, portanto, mais vulnerável à contaminação das águas subterrâneas.

  19. Residue preference mapping of ligand fragments in the Protein Data Bank.

    Science.gov (United States)

    Wang, Lirong; Xie, Zhaojun; Wipf, Peter; Xie, Xiang-Qun

    2011-04-25

    The interaction between small molecules and proteins is one of the major concerns for structure-based drug design because the principles of protein-ligand interactions and molecular recognition are not thoroughly understood. Fortunately, the analysis of protein-ligand complexes in the Protein Data Bank (PDB) enables unprecedented possibilities for new insights. Herein, we applied molecule-fragmentation algorithms to split the ligands extracted from PDB crystal structures into small fragments. Subsequently, we have developed a ligand fragment and residue preference mapping (LigFrag-RPM) algorithm to map the profiles of the interactions between these fragments and the 20 proteinogenic amino acid residues. A total of 4032 fragments were generated from 71 798 PDB ligands by a ring cleavage (RC) algorithm. Among these ligand fragments, 315 unique fragments were characterized with the corresponding fragment-residue interaction profiles by counting residues close to these fragments. The interaction profiles revealed that these fragments have specific preferences for certain types of residues. The applications of these interaction profiles were also explored and evaluated in case studies, showing great potential for the study of protein-ligand interactions and drug design. Our studies demonstrated that the fragment-residue interaction profiles generated from the PDB ligand fragments can be used to detect whether these fragments are in their favorable or unfavorable environments. The algorithm for a ligand fragment and residue preference mapping (LigFrag-RPM) developed here also has the potential to guide lead chemistry modifications as well as binding residues predictions.

  20. Diffusion and sorption of allyl isothiocyanate in the process of fumigation of maize Difusão e sorção do isotiocianato alilo no processo de fumigação do milho

    Directory of Open Access Journals (Sweden)

    Juliana L. Paes

    2011-03-01

    Full Text Available The purpose of this work was to evaluate the transport of allyl isothiocyanate (AITC by means of the sorption mechanism and the diffusion of AITC through maize grains. The experimental procedure to study the sorption mechanism was conducted by injection of AITC in glass flasks containing the grains. Kinetic models of zero, first and second order were fitted to AITC concentration data, with the purpose of determining the sorption rate (k. For the study of diffusion, a prototype was utilized in which the components are a gas chamber and a cylindrical column in which the grains were stored. At the interval of 110 min, samples in the chamber and in the column were collected, which were immediately injected into the gas chromatograph. In order to determine the effective diffusion coefficient (Def of AITC through maize grains, the term referring to the sorption rate was added to the diffusion equation. The kinetic model of the first order was the one that best fitted the experimental data for the sorption mechanism, and k was 6.26 x 10-4 s-1. The Def of AITC through grains was 7.2 x 10-3 cm² s-1. It was concluded that the transport of AITC through maize grains is slow, due to the low value of Def and high sorption rate of this component by the grains.Neste trabalho o propósito foi avaliar o transporte do isotiocianato alilo (AITC, por meio do estudo do mecanismo de sorção e da difusão do AITC, nos grãos de milho. O procedimento experimental para o estudo da sorção foi conduzido pela injeção de AITC em frascos de vidro contendo os grãos. Modelos cinéticos de ordem zero, de primeira e de segunda ordem, foram ajustados aos dados de concentração do AITC com a finalidade de determinar a taxa de sorção (k. Para o estudo da difusão utilizou-se um protótipo em que os componentes são uma câmara de gás e uma coluna cilíndrica, para contenção dos grãos. A cada 110 min amostras na câmara e na coluna foram coletadas e imediatamente

  1. Crystallization of protein–ligand complexes

    International Nuclear Information System (INIS)

    Hassell, Anne M.; An, Gang; Bledsoe, Randy K.; Bynum, Jane M.; Carter, H. Luke III; Deng, Su-Jun J.; Gampe, Robert T.; Grisard, Tamara E.; Madauss, Kevin P.; Nolte, Robert T.; Rocque, Warren J.; Wang, Liping; Weaver, Kurt L.; Williams, Shawn P.; Wisely, G. Bruce; Xu, Robert; Shewchuk, Lisa M.

    2007-01-01

    Methods presented for growing protein–ligand complexes fall into the categories of co-expression of the protein with the ligands of interest, use of the ligands during protein purification, cocrystallization and soaking the ligands into existing crystals. Obtaining diffraction-quality crystals has long been a bottleneck in solving the three-dimensional structures of proteins. Often proteins may be stabilized when they are complexed with a substrate, nucleic acid, cofactor or small molecule. These ligands, on the other hand, have the potential to induce significant conformational changes to the protein and ab initio screening may be required to find a new crystal form. This paper presents an overview of strategies in the following areas for obtaining crystals of protein–ligand complexes: (i) co-expression of the protein with the ligands of interest, (ii) use of the ligands during protein purification, (iii) cocrystallization and (iv) soaks

  2. -Pincer Ligand Family through Ligand Post-Modification

    KAUST Repository

    Huang, Mei-Hui; Hu, Jinsong; Huang, Kuo-Wei

    2017-01-01

    A series of air-stable nickel complexes containing triazine-based PN3P-pincer ligands were synthesized and fully characterized. Complex 3 contains a de-aromatized central triazine ring from the deprotonation of one of the N–H arms. With a post-modification strategy, the Me-PN3P*NiCl complex (3) could be converted into a new class of diimine–traizine PN3P-pincer nickel complexes.

  3. -Pincer Ligand Family through Ligand Post-Modification

    KAUST Repository

    Huang, Mei-Hui

    2017-10-02

    A series of air-stable nickel complexes containing triazine-based PN3P-pincer ligands were synthesized and fully characterized. Complex 3 contains a de-aromatized central triazine ring from the deprotonation of one of the N–H arms. With a post-modification strategy, the Me-PN3P*NiCl complex (3) could be converted into a new class of diimine–traizine PN3P-pincer nickel complexes.

  4. Reactivity of halide and pseudohalide ligands

    International Nuclear Information System (INIS)

    Kukushkin, Yu.N.

    1987-01-01

    Reactivity of halide and pseudohalide (cyanide, azide, thiocyanate, cyanate) ligands tending to form bridge bonds in transition metal (Re, Mo, W) complexes is considered. Complexes where transition metal salts are ligands of other, complex-forming ion, are described. Transformation of innerspheric pseudohalide ligands is an important way of directed synthesis of these metal coordination compounds

  5. Ligand-regulated peptide aptamers.

    Science.gov (United States)

    Miller, Russell A

    2009-01-01

    The peptide aptamer approach employs high-throughput selection to identify members of a randomized peptide library displayed from a scaffold protein by virtue of their interaction with a target molecule. Extending this approach, we have developed a peptide aptamer scaffold protein that can impart small-molecule control over the aptamer-target interaction. This ligand-regulated peptide (LiRP) scaffold, consisting of the protein domains FKBP12, FRB, and GST, binds to the cell-permeable small-molecule rapamycin and the binding of this molecule can prevent the interaction of the randomizable linker region connecting FKBP12 with FRB. Here we present a detailed protocol for the creation of a peptide aptamer plasmid library, selection of peptide aptamers using the LiRP scaffold in a yeast two-hybrid system, and the screening of those peptide aptamers for a ligand-regulated interaction.

  6. A method for fast energy estimation and visualization of protein-ligand interaction

    Science.gov (United States)

    Tomioka, Nobuo; Itai, Akiko; Iitaka, Yoichi

    1987-10-01

    A new computational and graphical method for facilitating ligand-protein docking studies is developed on a three-dimensional computer graphics display. Various physical and chemical properties inside the ligand binding pocket of a receptor protein, whose structure is elucidated by X-ray crystal analysis, are calculated on three-dimensional grid points and are stored in advance. By utilizing those tabulated data, it is possible to estimate the non-bonded and electrostatic interaction energy and the number of possible hydrogen bonds between protein and ligand molecules in real time during an interactive docking operation. The method also provides a comprehensive visualization of the local environment inside the binding pocket. With this method, it becomes easier to find a roughly stable geometry of ligand molecules, and one can therefore make a rapid survey of the binding capability of many drug candidates. The method will be useful for drug design as well as for the examination of protein-ligand interactions.

  7. Ligand binding by PDZ domains

    DEFF Research Database (Denmark)

    Chi, Celestine N.; Bach, Anders; Strømgaard, Kristian

    2012-01-01

    , for example, are particularly rich in these domains. The general function of PDZ domains is to bring proteins together within the appropriate cellular compartment, thereby facilitating scaffolding, signaling, and trafficking events. The many functions of PDZ domains under normal physiological as well...... as pathological conditions have been reviewed recently. In this review, we focus on the molecular details of how PDZ domains bind their protein ligands and their potential as drug targets in this context....

  8. Bitopic Ligands and Metastable Binding Sites

    DEFF Research Database (Denmark)

    Fronik, Philipp; Gaiser, Birgit I; Sejer Pedersen, Daniel

    2017-01-01

    of orthosteric binding sites. Bitopic ligands have been employed to address the selectivity problem by combining (linking) an orthosteric ligand with an allosteric modulator, theoretically leading to high-affinity subtype selective ligands. However, it remains a challenge to identify suitable allosteric binding...... that have been reported to date, this type of bitopic ligands would be composed of two identical pharmacophores. Herein, we outline the concept of bitopic ligands, review metastable binding sites, and discuss their potential as a new source of allosteric binding sites....

  9. Radioiodinated ligands for dopamine receptors

    International Nuclear Information System (INIS)

    Kung, H.F.

    1994-01-01

    The dopamine receptor system is important for normal brain function; it is also the apparent action site for various neuroleptic drugs for the treatment of schizophrenia and other metal disorders. In the past few years radioiodinated ligands for single photon emission tomography (SPECT) have been successfully developed and tested in humans: [ 123 I]TISCH for D1 dopamine receptors; [ 123 I]IBZM, epidepride, IBF and FIDA2, four iodobenzamide derivatives, for D2/D3 dopamine receptors. In addition, [ 123 I]β-CIT (RTI-55) and IPT, cocaine derivatives, for the dopamine reuptake site are potentially useful for diagnosis of loss of dopamine neurons. The first iodinated ligand, (R)trans-7-OH-PIPAT, for D3 dopamine receptors, was synthesized and characterized with cloned cell lines (Spodoptera frugiperda, Sf9) expressing the D2 and D3 dopamine receptors and with rat basal forebrain membrane preparations. Most of the known iodobenzamides displayed similar potency in binding to both D2 and D3 dopamine receptors expressed in the cell lines. Initial studies appear to suggest that by fine tuning the structures it may be possible to develop agents specific for D2 and D3 dopamine receptors. It is important to investigate D2/D3 selectivity for this series of potent ligands

  10. Histerese das isotermas de sorção da polpa de manga (Mangifera indica L. variedade manteiga Hysteresis of the sorption isotherms of mango pulp (Mangifera indica L. manteiga variety

    Directory of Open Access Journals (Sweden)

    Camila de S. Paglarini

    2013-03-01

    Full Text Available As isotermas de sorção são de grande importância para predizer processos de secagem e armazenamento de um produto. A histerese é um fenômeno que ocorre devido à diferença entre as curvas de adsorção e dessorção. O presente trabalho teve o objetivo de analisar a influência da temperatura nas isotermas de sorção e na histerese da polpa de manga variedade manteiga. As isotermas foram determinadas pelo método gravimétrico estático, com a utilização de diferentes concentrações ácidas, nas temperaturas de 20, 30, 40 e 50 °C e atividade de água variando de 4,3 a 88,8% até atingir a umidade de equilíbrio. Foram analisados seis modelos matemáticos para isotermas de sorção (GAB, BET, Halsey, Henderson-Thompson, Oswin e Luikov ajustados aos dados experimentais, através de regressão não-linear. A histerese foi calculada pela área compreendida entre as curvas de dessorção e adsorção. De acordo com os resultados obtidos o modelo de GAB foi o que melhor se ajustou às isotermas de equilíbrio da manga. A área da histerese reduziu 51% entre as temperaturas de 20 e 50 °C.The sorption isotherms are of great importance for predicting drying and storage of a product. Hysteresis is a phenomenon that occurs due to the difference between the curves of adsorption and desorption. This study aimed to analyse the influence of temperature on sorption isotherms and hysteresis of mango pulp manteiga variety. The isotherms were determined by the static method with the use of different acid concentrations. The samples were submitted to temperatures of 20, 30, 40 and 50 °C and water activity ranging from 4.3 to 88.8% until the equilibrium moisture content. Six mathematical models for the sorption isotherms (GAB, BET, Halsey, Henderson-Thompson, Oswin and Luikov were analysed and adjusted to the experimental data using nonlinear regression. The hysteresis was calculated as the area between the curves of adsorption and desorption

  11. Contrasting roles for TLR ligands in HIV-1 pathogenesis.

    Directory of Open Access Journals (Sweden)

    Beda Brichacek

    2010-09-01

    Full Text Available The first line of a host's response to various pathogens is triggered by their engagement of cellular pattern recognition receptors (PRRs. Binding of microbial ligands to these receptors leads to the induction of a variety of cellular factors that alter intracellular and extracellular environment and interfere directly or indirectly with the life cycle of the triggering pathogen. Such changes may also affect any coinfecting microbe. Using ligands to Toll-like receptors (TLRs 5 and 9, we examined their effect on human immunodeficiency virus (HIV-1 replication in lymphoid tissue ex vivo. We found marked differences in the outcomes of such treatment. While flagellin (TLR5 agonist treatment enhanced replication of CC chemokine receptor 5 (CCR 5-tropic and CXC chemokine receptor 4 (CXCR4-tropic HIV-1, treatment with oligodeoxynucleotide (ODN M362 (TLR9 agonist suppressed both viral variants. The differential effects of these TLR ligands on HIV-1 replication correlated with changes in production of CC chemokines CCL3, CCL4, CCL5, and of CXC chemokines CXCL10, and CXCL12 in the ligand-treated HIV-1-infected tissues. The nature and/or magnitude of these changes were dependent on the ligand as well as on the HIV-1 viral strain. Moreover, the tested ligands differed in their ability to induce cellular activation as evaluated by the expression of the cluster of differentiation markers (CD 25, CD38, CD39, CD69, CD154, and human leukocyte antigen D related (HLA-DR as well as of a cell proliferation marker, Ki67, and of CCR5. No significant effect of the ligand treatment was observed on apoptosis and cell death/loss in the treated lymphoid tissue ex vivo. Our results suggest that binding of microbial ligands to TLRs is one of the mechanisms that mediate interactions between coinfected microbes and HIV-1 in human tissues. Thus, the engagement of appropriate TLRs by microbial molecules or their mimetic might become a new strategy for HIV therapy or prevention.

  12. Ut pictura poesis y la construcción espaciotemporal de las imágenes literarias en «El divino Narciso» de sor Juana Inés de la Cruz

    Directory of Open Access Journals (Sweden)

    Robin Ann Rice

    2018-06-01

    Full Text Available En contraposición a las teorías tradicionales sobre el lenguaje, este artículo propone que la presencia de Ut pictura poesis textual denota una literatura ilustrativa que se comprende sincrónicamente y, por lo tanto, produce un constructo espaciotemporal. El propósito del estudio es el de examinar El divino Narciso de sor Juana Inés de la Cruz y analizar ciertas técnicas empleadas tales como imágenes literarias plásticas, en particular, los bloques alegóricos, los emblemas y las evocaciones de imágenes tan reconocidas que con una simple mención de su tema, los espectadores habrían podido recrearlas en su imaginación gracias a procesos cognitivos espaciotemporales.

  13. Isotermas de sorção de tâmaras: determinação experimental e avaliação de modelos matemáticos Dates sorption isotherms: experimental determination and mathematics models evaluation

    Directory of Open Access Journals (Sweden)

    Mônica E.T. PRADO

    1999-01-01

    Full Text Available As isotermas de sorção de tâmaras (Phoenix dactylifera L., da variedade Zahidi, foram determinadas para três temperaturas, 60, 70 e 80° C pelo método estático gravimétrico. As curvas experimentais foram ajustadas pelas equações de BET, BET linearizada, GAB, HALSEY, OSWIN e PELEG. O desvio relativo entre os valores experimentais e os valores estimados foi calculado para cada curva, a fim de se avaliar qual equação melhor se ajustou aos dados experimentais.Dates sorption isotherms were determined by gravimetric at three differents temperatures (60, 70 and 80° C. Experimental data was adjusted to six sorption models de BET, linear BET, GAB, HALSEY, OSWIN and PELEG. The average relative deviations between calculated and experimental data were calculated do select best fit model.

  14. Mixed-ligand Pt(II) dithione-dithiolato complexes: influence of the dicyanobenzodithiolato ligand on the second-order NLO properties.

    Science.gov (United States)

    Espa, Davide; Pilia, Luca; Marchiò, Luciano; Artizzu, Flavia; Serpe, Angela; Mercuri, Maria Laura; Simão, Dulce; Almeida, Manuel; Pizzotti, Maddalena; Tessore, Francesca; Deplano, Paola

    2012-03-28

    The mixed-ligand dithiolene complex [Pt(Bz(2)pipdt)(dcbdt)] (1) bearing the two ligands Bz(2)pipdt = 1,4-dibenzyl-piperazine-3,2-dithione and dcbdt = dicyanobenzodithiolato, has been synthesized, characterized and studied to evaluate its second-order optical nonlinearity. The dithione/dithiolato character of the two ligands gives rise to an asymmetric distribution of the charge in the molecule. This is reflected by structural data showing that in the C(2)S(2)PtS(2)C(2) dithiolene core the four sulfur atoms define a square-planar coordination environment of the metal where the Pt-S bond distances involving the two ligands are similar, while the C-S bond distances in the C(2)S(2) units exhibit a significant difference in Bz(2)pipdt (dithione) and dcbdt (dithiolato). 1 shows a moderately strong absorption peak in the visible region, which can be related to a HOMO-LUMO transition, where the dcbdt ligand (dithiolato) contributes mostly to the HOMO, and the Bz(2)pipdt one (dithione) mostly to the LUMO. Thus this transition has ligand-to-ligand charge transfer (CT) character with some contribution of the metal and undergoes negative solvatochromism and molecular quadratic optical nonlinearity (μβ(0) = -1296 × 10(-48) esu), which was determined by the EFISH (electric-field-induced second-harmonic generation) technique and compared with the values of similar complexes on varying the dithiolato ligand (mnt = maleonitriledithiolato, dmit = 2-thioxo-1,3-dithiole-4,5-dithiolato). Theoretical calculations help to elucidate the role of the dithiolato ligands in affecting the molecular quadratic optical nonlinearity of these complexes.

  15. Simulação do transporte e da sorção de imazaquin em colunas de solo Simulation of imazaquin transport and sorption in soil columns

    Directory of Open Access Journals (Sweden)

    Robson Rolland Monticelli Barizon

    2006-08-01

    Full Text Available Dentre os métodos disponíveis para avaliar o comportamento de agrotóxicos no solo, destacam-se o método "batch" (análise em batelada e o deslocamento miscível. O objetivo deste estudo foi avaliar a sorção e a mobilidade do imazaquin em solos com diferentes características químicas, físicas e mineralógicas, utilizando as técnicas de deslocamento miscível e "batch". Os ensaios foram realizados no laboratório de Ecotoxicologia do Centro de Energia Nuclear na Agricultura da Universidade de São Paulo (CENA/USP, Piracicaba, São Paulo. Os solos utilizados, classificados como Neossolo Quartzarênico (RQ, Latossolo Vermelho-Amarelo (LVA e Latossolo Vermelho distroférrico (LVdf, foram secos ao ar e peneirados em malha 2 mm, sendo então procedida a caracterização química, física e mineralógica das amostras. Foi selecionada para o estudo a molécula do Imazaquin. No ensaio do deslocamento miscível, foi aplicada uma solução de CaCl2, obtendo-se uma curva de eluição do Cl-, utilizado como traçador. As curvas de eluição do Cl- foram ajustadas a um modelo baseado na equação de convecção-dispersão para transporte ideal. Após a eluição do Cl-, aplicou-se a solução que continha 14C-imazaquin que gerou as curvas de eluição para esta molécula. A curva foi ajustada a um modelo bicontínuo que considera o não-equilíbrio durante o transporte. No ensaio de sorção com o método "batch", foram utilizadas soluções de imazaquin radiomarcado variando de 0,67 a 10,72 mmol L-1 para obtenção das isotermas ajustadas pela equação de Freundlich. A taxa de lixiviação foi alta para todos os solos, sendo maior para o RQ. As curvas de eluição do Cl- foram simétricas para todos os solos e apresentaram um bom ajuste ao modelo que considera o transporte ideal, indicando que não houve não-equilíbrio relacionado com o transporte. Para o imazaquin, as curvas de eluição foram assimétricas, com prolongamento da parte posterior

  16. Insights into an original pocket-ligand pair classification: a promising tool for ligand profile prediction.

    Directory of Open Access Journals (Sweden)

    Stéphanie Pérot

    Full Text Available Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely

  17. Insights into an original pocket-ligand pair classification: a promising tool for ligand profile prediction.

    Science.gov (United States)

    Pérot, Stéphanie; Regad, Leslie; Reynès, Christelle; Spérandio, Olivier; Miteva, Maria A; Villoutreix, Bruno O; Camproux, Anne-Claude

    2013-01-01

    Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely, some key pocket

  18. Ligand photo-isomerization triggers conformational changes in iGluR2 ligand binding domain.

    Directory of Open Access Journals (Sweden)

    Tino Wolter

    Full Text Available Neurological glutamate receptors bind a variety of artificial ligands, both agonistic and antagonistic, in addition to glutamate. Studying their small molecule binding properties increases our understanding of the central nervous system and a variety of associated pathologies. The large, oligomeric multidomain membrane protein contains a large and flexible ligand binding domains which undergoes large conformational changes upon binding different ligands. A recent application of glutamate receptors is their activation or inhibition via photo-switchable ligands, making them key systems in the emerging field of optochemical genetics. In this work, we present a theoretical study on the binding mode and complex stability of a novel photo-switchable ligand, ATA-3, which reversibly binds to glutamate receptors ligand binding domains (LBDs. We propose two possible binding modes for this ligand based on flexible ligand docking calculations and show one of them to be analogues to the binding mode of a similar ligand, 2-BnTetAMPA. In long MD simulations, it was observed that transitions between both binding poses involve breaking and reforming the T686-E402 protein hydrogen bond. Simulating the ligand photo-isomerization process shows that the two possible configurations of the ligand azo-group have markedly different complex stabilities and equilibrium binding modes. A strong but slow protein response is observed after ligand configuration changes. This provides a microscopic foundation for the observed difference in ligand activity upon light-switching.

  19. Synthesis and complexation of acyclic dithiolate ligands

    International Nuclear Information System (INIS)

    Ashford, L.

    1999-11-01

    Four approaches to ring substituted and unsubstituted N,N'-bis(o-mercaptobenzyliden)propylenediaminate ligands are described using N,N-dimethylcarbamate as a thiolate protecting group. Of the four basic methods, substitution, reduction, rearrangement and oxidation, the latter two successfully synthesise the aldehyde precursor. Rearrangement of the thiocarbamoyl group to the protected thiophenol is shown to be facilitated by a para-nitro substiuent. Ni(II) and Cu(II) complexes of N,N'-bis(p-nitro-o-mercaptobenzyliden)-propylenediaminate are synthesised by reaction of 2-formyl-4-nitro-N,N-dimethylcarbamoyI thiophenol, [Ni(OAc) 2 ].4(H 2 O) and 1,3-diaminopropane. The para-unsubstituted Ni(II) complex, Nickel-[N,N'-bis(o-mercaptobenzyliden) propylenediaminate] is prepared via reaction of the aldehyde, 2-formyl-N,N-dimethylcarbamoyl thiophenol with [Ni(OAc) 2 ].4(H 2 O) and 1,3-diaminopropane. The analogous carbamoyl-protected amine ligands, N,N'-dimethyl-N.N'-di[2-(N'',N''-dimethylcarbamyl)mercapto] benzyl-1,3-propane-diamine and N,N'-dimethyl-N,N'-di[2-(N'',N''-dimethylcarbamyl)mercapto] benzyl-1,2-ethane-diamine are also studied. The tertiary-butyl-protected diimine ligand, N,N'-bis-(o-mercaptobenzylidene)-propylenediaminate is prepared from 2-(tert-butylsulfanyl)benzaldehyde and 1,3-diaminopropane. Reaction with [Ni(H 2 O) 6 ]Cl 2 gives Nickel-[N,N'-bis(o-mercaptobenzyliden)-propylenediaminate], the crystal structure showing a distorted square-planar Ni(II) centre. Reaction with ZnCl 2 gives Zinc-[N,N'-bis(o-mercaptobenzyliden)propylenediaminate]dichloride. The crystal structure shows the thiolate donors remain protected and uncoordinated. The Zn(II) ion is coordinated by two imine donors and two chloride ions in a tetrahedral environment. In reactions with Ag(I) and Hg(II), N,N'-bis-(o-mercaptobenzylidene)-propylenediaminate acts as a reductant giving the free metals. Structural data and NMR and IR spectroscopic data for Nickel

  20. Development of immobilized ligands for actinide separations

    International Nuclear Information System (INIS)

    Paine, R.T.

    1994-01-01

    Primary goals during this grant period were to (1) synthesize new bifunctional chelating ligands, (2) characterize the structural features of the Ln and An coordination complexes formed by these ligands, (3) use structural data to iteratively design new classes of multifunctional ligands, and (4) explore additional routes for attachment of key ligands to solid supports that could be useful for chromatographic separations. Some highlights of recently published work as well as a summary of submitted, unpublished and/or still in progress research are outlined

  1. Automatic generation of bioinformatics tools for predicting protein-ligand binding sites.

    Science.gov (United States)

    Komiyama, Yusuke; Banno, Masaki; Ueki, Kokoro; Saad, Gul; Shimizu, Kentaro

    2016-03-15

    Predictive tools that model protein-ligand binding on demand are needed to promote ligand research in an innovative drug-design environment. However, it takes considerable time and effort to develop predictive tools that can be applied to individual ligands. An automated production pipeline that can rapidly and efficiently develop user-friendly protein-ligand binding predictive tools would be useful. We developed a system for automatically generating protein-ligand binding predictions. Implementation of this system in a pipeline of Semantic Web technique-based web tools will allow users to specify a ligand and receive the tool within 0.5-1 day. We demonstrated high prediction accuracy for three machine learning algorithms and eight ligands. The source code and web application are freely available for download at http://utprot.net They are implemented in Python and supported on Linux. shimizu@bi.a.u-tokyo.ac.jp Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

  2. Macrocyclic ligands for uranium complexation

    International Nuclear Information System (INIS)

    Potts, K.T.

    1991-04-01

    A highly preorganized 24-macrocycle containing biuret, thiobiuret and pyridine subunits has been prepared by high dilution ring-closure procedures. Intermediate products to this macrocycle have been utilized to extend this synthetic route to include further representatives where solubility and stability will be influenced by substituent variation. A 1:1 complex has been formed from uranyl acetate and a quinquepyridine derivative, this representing a new type of ligand for the uranyl ion. A very convenient synthetic procedure that will allow the incorporation of these macrocycles into polymeric systems has been developed for the introduction of a vinyl substituent into the 4-position of the pyridine ring. Using triflate, vinyltributyltin and Pd 0 chemistry, this procedure should make a variety of substituted 4-vinylpyridines available for the first time. 3 refs

  3. Reverse depletion effects and the determination of ligand density on some spherical bioparticles

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Chunxiang [Heilongjiang Bayi Agricultural University (China); Liu, Yanhui, E-mail: ionazati@itp.ac.cn; Fan, Yangtao; Liu, Yijun; Li, Qiancheng; Xu, Houqiang, E-mail: houqiangxu@yahoo.com [Guizhou University (China)

    2016-06-15

    In cell environments crowded with macromolecules, the depletion effects act and assist in the assembly of a wide range of cellular structures, from the cytoskeleton to the chromatin loop, which are well accepted. But a recent quantum dot experiment indicated that the dimensions of the receptor–ligand complex have strong effects on the size-dependent exclusion of proteins in cell environments. In this article, a continuum elastic model is constructed to resolve the competition between the dimension of the receptor–ligand complex and depletion effects in the endocytosis of a spherical virus-like bioparticle. Our results show that the depletion effects do not always assist endocytosis of a spherical virus-like bioparticle; while the dimension of the ligand–receptor complex is larger than the size of a small bioparticle in cell environments, the depletion effects do not work and reverse effects appear. The ligand density covered on the virus can be identified quantitatively.

  4. CXCR4 Ligands : The Next Big Hit?

    NARCIS (Netherlands)

    Walenkamp, Annemiek M. E.; Lapa, Constantin; Herrmann, Ken; Wester, Hans-Juergen

    2017-01-01

    The G protein-coupled protein receptor C-X-C chemokine receptor 4 (CXCR4) is an attractive target for cancer diagnosis and treatment, as it is overexpressed in many solid and hematologic cancers. Binding of its ligand, C-X-C chemokine ligand 12 (CXCL12), results in receptor internalization and

  5. Ligand-receptor Interactions by NMR Spectroscopy

    Directory of Open Access Journals (Sweden)

    Novak. P.

    2008-04-01

    Full Text Available Today NMR spectroscopy is a method of choice for elucidation of interactions between biomolecules and the potential ligands. Knowledge on these interactions is an essential prerequisite for the rational drug design. The most important contribution of NMR to drug design a few years ago was the 3D structure determination of proteins. Besides delivering the 3D structures of the free proteins as a raw material for the modeling studies on ligand binding, NMR can directly yield valuable experimental data on the biologically important protein-ligand complexes. In addition to X-ray diffraction, NMR spectroscopy can provide information on the internal protein dynamics ordynamics of intermolecular interactions. Changes in NMR parameters allow us to detect ("SAR by NMR" and quantitatively determine binding affinities (titration, diffusion NMR experiments, etc. of potential ligands. Also, it is possible to determine the binding site and conformations of ligands, receptors and receptor-ligand complexes with the help of NMR methods such as tr-NOESY. Epitopes or functional groups responsible for binding of ligands to the receptor can be identified by employing STD or WaterLOGSY experiments. In this review are described some of the most frequent NMR methods for the characterization of the interactions between biomolecules and ligands, together with their advantages and disadvantages.

  6. Autocrine signal transmission with extracellular ligand degradation

    Science.gov (United States)

    Muratov, C B; Posta, F; Shvartsman, S Y

    2009-03-01

    Traveling waves of cell signaling in epithelial layers orchestrate a number of important processes in developing and adult tissues. These waves can be mediated by positive feedback autocrine loops, a mode of cell signaling where binding of a diffusible extracellular ligand to a cell surface receptor can lead to further ligand release. We formulate and analyze a biophysical model that accounts for ligand-induced ligand release, extracellular ligand diffusion and ligand-receptor interaction. We focus on the case when the main mode for ligand degradation is extracellular and analyze the problem with the sharp threshold positive feedback nonlinearity. We derive expressions that link the speed of propagation and other characteristics of traveling waves to the parameters of the biophysical processes, such as diffusion rates, receptor expression level, etc. Analyzing the derived expressions we found that traveling waves in such systems can exhibit a number of unusual properties, e.g. non-monotonic dependence of the speed of propagation on ligand diffusivity. Our results for the fully developed traveling fronts can be used to analyze wave initiation from localized perturbations, a scenario that frequently arises in the in vitro models of epithelial wound healing, and guide future modeling studies of cell communication in epithelial layers.

  7. Organotellurium ligands – designing and complexation reactions

    Indian Academy of Sciences (India)

    Unknown

    membered rings it is negative and ~30 ppm only. Keywords. Organotellurium ligands; hybrid telluroether; platinum metal complexes; tellurium-125 NMR. 1. Introduction. Tellurium is the noblest metalloid which may act as a Lewis acid as well as Lewis base. The ligand chemistry of tellurium, which acts as a 'soft' donor, was ...

  8. Is the isolated ligand binding domain a good model of the domain in the native receptor?

    Science.gov (United States)

    Deming, Dustin; Cheng, Qing; Jayaraman, Vasanthi

    2003-05-16

    Numerous studies have used the atomic level structure of the isolated ligand binding domain of the glutamate receptor to elucidate the agonist-induced activation and desensitization processes in this group of proteins. However, no study has demonstrated the structural equivalence of the isolated ligand binding fragments and the protein in the native receptor. In this report, using visible absorption spectroscopy we show that the electronic environment of the antagonist 6-cyano-7-nitro-2,3-dihydroxyquinoxaline is identical for the isolated protein and the native glutamate receptors expressed in cells. Our results hence establish that the local structure of the ligand binding site is the same in the two proteins and validate the detailed structure-function relationships that have been developed based on a comparison of the structure of the isolated ligand binding domain and electrophysiological consequences in the native receptor.

  9. Heterogeneity and dynamics of the ligand recognition mode in purine-sensing riboswitches.

    Science.gov (United States)

    Jain, Niyati; Zhao, Liang; Liu, John D; Xia, Tianbing

    2010-05-04

    High-resolution crystal structures and biophysical analyses of purine-sensing riboswitches have revealed that a network of hydrogen bonding interactions appear to be largey responsible for discrimination of cognate ligands against structurally related compounds. Here we report that by using femtosecond time-resolved fluorescence spectroscopy to capture the ultrafast decay dynamics of the 2-aminopurine base as the ligand, we have detected the presence of multiple conformations of the ligand within the binding pockets of one guanine-sensing and two adenine-sensing riboswitches. All three riboswitches have similar conformational distributions of the ligand-bound state. The known crystal structures represent the global minimum that accounts for 50-60% of the population, where there is no significant stacking interaction between the ligand and bases of the binding pocket, but the hydrogen-bonding cage collectively provides an electronic environment that promotes an ultrafast ( approximately 1 ps) charge transfer pathway. The ligand also samples multiple conformations in which it significantly stacks with either the adenine or the uracil bases of the A21-U75 and A52-U22 base pairs that form the ceiling and floor of the binding pocket, respectively, but favors the larger adenine bases. These alternative conformations with well-defined base stacking interactions are approximately 1-1.5 kcal/mol higher in DeltaG degrees than the global minimum and have distinct charge transfer dynamics within the picosecond to nanosecond time regime. Inside the pocket, the purine ligand undergoes dynamic motion on the low nanosecond time scale, sampling the multiple conformations based on time-resolved anisotropy decay dynamics. These results allowed a description of the energy landscape of the bound ligand with intricate details and demonstrated the elastic nature of the ligand recognition mode by the purine-sensing riboswitches, where there is a dynamic balance between hydrogen bonding

  10. Sorção de potássio em amostras de solo submetidas à aplicação de vinhaça Sorption of potassium in soil submitted to application of vinasse

    Directory of Open Access Journals (Sweden)

    Lorena M. Nicochelli

    2012-07-01

    Full Text Available No processo de produção do etanol a vinhaça é um subproduto gerado em grande escala, em média, na razão de aproximadamente 13 L de vinhaça por litro de álcool destilado. Este volume produzido representa um problema no acondicionamento e nos processos de tratamento deste efluente que, na maioria das vezes, é lançado no solo por fertirrigação. Tendo em vista os altos teores de nutrientes, com destaque para o potássio e o alto teor de matéria orgânica, a disposição da vinhaça no solo necessita de estudos, uma vez que pode ocorrer lixiviação de vários desses elementos às águas subsuperficiais. Foram realizados ensaios de batelada, o que permitiu a avaliação do efeito de diferentes fatores, como a variação da razão solo: solução e do tempo de contato na sorção do potássio em três amostras de solo distintas, submetidas à aplicação de vinhaça. Nos ensaios com razão solo:solução 1:50; em todas as amostras, houve maior sorção que na razão 1:4. O tempo de contato ideal para estabelecimento das condições de equilíbrio foi 24 h. Dentre as amostras estudadas a maior sorção foi constatada para a amostra com maior percentual de argila em sua composição e maior capacidade de troca catiônica.In the process of producing ethanol, vinasse is a by-product generated in large scale, on average, at a rate around 13 L of vinasse per liter of distilled alcohol. This volume represents a problem in conditioning and treatment processes of this wastewater, which most of time is incorporated into the soil by fertigation. Considering the high levels of nutrients, especially potassium and the high content of organic matter, the disposal of vinasse into the soil needs further studies, because there may be leaching of several elements to groundwater. Batch tests were performed, which allowed assessment of the effect of different factors such as variation of the soil to solution ratio and the variation of contact time between

  11. Correcting ligands, metabolites, and pathways

    Directory of Open Access Journals (Sweden)

    Vriend Gert

    2006-11-01

    Full Text Available Abstract Background A wide range of research areas in bioinformatics, molecular biology and medicinal chemistry require precise chemical structure information about molecules and reactions, e.g. drug design, ligand docking, metabolic network reconstruction, and systems biology. Most available databases, however, treat chemical structures more as illustrations than as a datafield in its own right. Lack of chemical accuracy impedes progress in the areas mentioned above. We present a database of metabolites called BioMeta that augments the existing pathway databases by explicitly assessing the validity, correctness, and completeness of chemical structure and reaction information. Description The main bulk of the data in BioMeta were obtained from the KEGG Ligand database. We developed a tool for chemical structure validation which assesses the chemical validity and stereochemical completeness of a molecule description. The validation tool was used to examine the compounds in BioMeta, showing that a relatively small number of compounds had an incorrect constitution (connectivity only, not considering stereochemistry and that a considerable number (about one third had incomplete or even incorrect stereochemistry. We made a large effort to correct the errors and to complete the structural descriptions. A total of 1468 structures were corrected and/or completed. We also established the reaction balance of the reactions in BioMeta and corrected 55% of the unbalanced (stoichiometrically incorrect reactions in an automatic procedure. The BioMeta database was implemented in PostgreSQL and provided with a web-based interface. Conclusion We demonstrate that the validation of metabolite structures and reactions is a feasible and worthwhile undertaking, and that the validation results can be used to trigger corrections and improvements to BioMeta, our metabolite database. BioMeta provides some tools for rational drug design, reaction searches, and

  12. Autocrine signal transmission with extracellular ligand degradation

    International Nuclear Information System (INIS)

    Muratov, C B; Posta, F; Shvartsman, S Y

    2009-01-01

    Traveling waves of cell signaling in epithelial layers orchestrate a number of important processes in developing and adult tissues. These waves can be mediated by positive feedback autocrine loops, a mode of cell signaling where binding of a diffusible extracellular ligand to a cell surface receptor can lead to further ligand release. We formulate and analyze a biophysical model that accounts for ligand-induced ligand release, extracellular ligand diffusion and ligand–receptor interaction. We focus on the case when the main mode for ligand degradation is extracellular and analyze the problem with the sharp threshold positive feedback nonlinearity. We derive expressions that link the speed of propagation and other characteristics of traveling waves to the parameters of the biophysical processes, such as diffusion rates, receptor expression level, etc. Analyzing the derived expressions we found that traveling waves in such systems can exhibit a number of unusual properties, e.g. non-monotonic dependence of the speed of propagation on ligand diffusivity. Our results for the fully developed traveling fronts can be used to analyze wave initiation from localized perturbations, a scenario that frequently arises in the in vitro models of epithelial wound healing, and guide future modeling studies of cell communication in epithelial layers

  13. Radiation induced ligand loss from cobalt complexes

    International Nuclear Information System (INIS)

    Funston, A. M.; McFadyen, W.D.; Tregloan, P.A.

    2000-01-01

    Full text: Due to the rapid nature of ligand dissociation from cobalt(II) complexes the study of the rate of ligand dissociation necessitates the use of a technique such as pulse radiolysis. This allows the rapid reduction of the corresponding cobalt(III) complex by a reducing radical, such as the aquated electron, to form the cobalt(II) complex. However, to date, no systematic study of either the mechanism of reduction or the influence of the electronic structure on the rate of ligand dissociation has been carried out. In order to understand these processes more fully the mechanism of reduction of a range of related cobalt(III) complexes by the aquated electron and the subsequent rate of ligand dissociation from the resulting cobalt(II) complexes is being investigated. It has been found that a number of processes are observed following the initial rapid reaction of the cobalt(III) complex with the aquated electron. Ultimately ligand loss is observed. Depending upon the complex, the initial processes observed may include the formation of coordinated radicals and electron transfer within the complex. For complexes containing aromatic ligands such as 2,2'-bipyridine, 1,10-phenanthroline and dipyrido[3,2-a:2',3'-c]phenazine the formation of a coordinated radical is observed as the initial reduction step. The kinetics of ligand dissociation of these complexes has been determined. The loss of monodentate ligands is fast and has been indistinguishable from the reduction processes when aromatic ligands are also present in the complex. However, for diamine chelates and diimine chelates spectra of the transient species can be resolved

  14. Labeled receptor ligands for spect

    International Nuclear Information System (INIS)

    Kung, H.F.

    1989-01-01

    Receptor specific imaging agents for single photon emission computed tomography (SPECT) can potentially be useful in the understanding of basic biochemistry and pharmacology of receptors. SPECT images may also provide tools for evaluation of density and binding kinetics of a specific receptor, information important for diagnosis and patient management. Basic requirements for receptor imaging agents are: (a) they are labeled with short-lived isotopes, (b) they show high selectivity and specific uptake, (c) they exhibit high target/background ratio, and (d) they can be modeled to obtain quantitative information. Several good examples of CNS receptor specific ligands labeled with I-123 have been developed, including iodoQNB, iodoestrogen iodobenzadiazepine, iodobenazepine, iodobenzamides for muscarinic, estrogen benzadiazepine, D-1 and D-2 dopamine receptors. With the advent of newer and faster SPECT imaging devices, it may be feasible to quantitate the receptor density by in vivo imaging techniques. These new brain imaging agents can provide unique diagnostic information, which may not be available through other imaging modalities, such as CT and MRI

  15. A Versatile Dinucleating Ligand Containing Sulfonamide Groups

    DEFF Research Database (Denmark)

    Sundberg, Jonas; Witt, Hannes; Cameron, Lisa

    2014-01-01

    ligand can be prepared in aqueous solutions using only divalent metal ions. Two of the copper(II) complexes, [Cu2(psmp)(OH)] and [Cu2(psmp)(OAc)2]-, demonstrate the anticipated 1:2 ligand/metal stoichiometry and show that the dimetallic binding site created for exogenous ligands possesses high inherent...... of antiferromagnetic coupling. This is corroborated computationally by broken-symmetry density functional theory, which for isotropic modeling of the coupling predicts an antiferromagnetic coupling strength of J = 70.5 cm-1....

  16. Sorção de atrazina e de mesotriona em latossolos e estimativa do potencial de contaminação

    Directory of Open Access Journals (Sweden)

    Rosane Martinazzo

    2011-01-01

    Full Text Available Following application herbicides usually reach the soil and undergo several dissipation processes which determine their effects on target organisms and on the environment. This work aimed to evaluate atrazine and mesotrione sorption in Oxisols and estimate their potential impact on the environment. We observed that atrazine sorption was influenced by soil organic matter content and its hydrophobic character. Clay fraction was the main factor influencing mesotrione sorption followed in a lesser extent by soil organic matter content. In contrast to atrazine, mesotrione retention was favored by the higher carboxylic substitution in the aliphatic chains of soil organic matter. Atrazine and mesotrione were considered compounds that are likely to pose an appreciable risk of causing deleterious effects on the environment.

  17. Ligand based pharmacophore modelling of anticancer histone ...

    African Journals Online (AJOL)

    USER

    2010-06-21

    Jun 21, 2010 ... The study was carried out using the software Ligand Scout (version .... Computer Science, for his great help and support. We are also grateful to Faculty of Engineering and applied. Sciences, Mohammad .... Aided Mol. Design ...

  18. Synthesis and characterization β-ketoamine ligands

    Science.gov (United States)

    Zaid, Nurzati Amani Mohamed; Hassan, Nur Hasyareeda; Karim, Nurul Huda Abd

    2018-04-01

    β-ketoamine ligands are important members of heterodonor ligand because of their ease of preparation and modification of both steric and/or electronic effects. Complexes with β-ketoamine has received much less attention and there has been no study about this complex with β-ketoamine in ionic liquid reported. Two type of β-ketoamine ligands which are 4-amino-3-pentene-2-onato (A) and 3-amino-2-butenoic acid methyl ester (B) have been synthesized in this work. The resulting compound formed was characterized using standard spectroscopic and structural techniques which includes 1H and 13C, NMR spectroscopy and FTIR spectroscopy. The 1H and 13C NMR spectrum displayed all the expected signals with correct integration and multiplicity. And it is proved that there are some differences between two ligands as observed in NMR and FTIR spectrum.

  19. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Clouse, Katherine N; Goodrich, Jennifer S

    2006-01-01

    ...) activity has been associated with an increased prognosis of breast cancer. During cogenesis in Drosophila melanogaster local Egfr activation by the spatially-restricted TGFalpha-like ligand Gurken (Grk...

  20. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Goodrich, Jennifer S

    2005-01-01

    ...) activity has been associated with an increased prognosis of breast cancer. During oogenesis in Drosophila melanogaster, local EGFR activation by the spatially restricted TGF alpha-like ligand, Gurken (Grk...

  1. Bystander protein protects potential vaccine-targeting ligands against intestinal proteolysis.

    Science.gov (United States)

    Reuter, Fabian; Bade, Steffen; Hirst, Timothy R; Frey, Andreas

    2009-07-20

    Endowing mucosal vaccines with ligands that target antigen to mucosal lymphoid tissues may improve immunization efficacy provided that the ligands withstand the proteolytic environment of the gastro-intestinal tract until they reach their destination. Our aim was to investigate whether and how three renowned ligands - Ulex europaeus agglutinin I and the B subunits of cholera toxin and E. coli heat-labile enterotoxin - master this challenge. We assessed the digestive power of natural murine intestinal fluid (natIF) using assays for trypsin, chymotrypsin and pancreatic elastase along with a test for nonspecific proteolysis. The natIF was compared with simulated murine intestinal fluid (simIF) that resembled the trypsin, chymotrypsin and elastase activities of its natural counterpart but lacked or contained albumins as additional protease substrates. The ligands were exposed to the digestive fluids and degradation was determined. The studies revealed that (i) the three pancreatic endoproteases constitute only one third of the total protease activity of natIF and (ii) the ligands resist proteolysis in natIF and protein-enriched simIF over 3 h but (iii) are partially destroyed in simIF that lacks additional protease substrate. We assume that the proteins of natIF are preferred substrates for the intestinal proteases and thus can protect vaccine-targeting ligands from destruction.

  2. Remediation of lead-contaminated soil with non-toxic biodegradable natural ligands extracted from soybean.

    Science.gov (United States)

    Lee, Yong-Woo; Kim, Chulsung

    2012-01-01

    Bench-scale soil washing studies were performed to evaluate the potential application of non-toxic, biodegradable extracted soybean-complexing ligands for the remediation of lead-contaminated soils. Results showed that, with extracted soybean-complexing ligands, lead solubility extensively increased when pH of the solution was higher than 6, and approximately 10% (500 mg/kg) of lead was removed from a rifle range soil. Two potential primary factors controlling the effectiveness of lead extraction from lead-contaminated soils with natural ligands are adsorption of extracted aqueous lead ions onto the ground soybean and the pH of the extraction solution. More complexing ligands were extracted from the ground soybean as the reaction pH increased. As a result, significantly higher lead extraction efficiency was observed under basic environments. In addition, less adsorption onto soybean was observed when the pH of the solution was higher than 7. Among two available Lewis base functional groups in the extracted soybean-complexing ligands such as carboxylate and the alpha-amino functional groups, the non-protonated alpha-amino functional groups may play an important role for the dissolution of lead from lead-contaminated soil through the formation of soluble lead--ligand complexes.

  3. Cell-specific targeting by heterobivalent ligands.

    Science.gov (United States)

    Josan, Jatinder S; Handl, Heather L; Sankaranarayanan, Rajesh; Xu, Liping; Lynch, Ronald M; Vagner, Josef; Mash, Eugene A; Hruby, Victor J; Gillies, Robert J

    2011-07-20

    Current cancer therapies exploit either differential metabolism or targeting to specific individual gene products that are overexpressed in aberrant cells. The work described herein proposes an alternative approach--to specifically target combinations of cell-surface receptors using heteromultivalent ligands ("receptor combination approach"). As a proof-of-concept that functionally unrelated receptors can be noncovalently cross-linked with high avidity and specificity, a series of heterobivalent ligands (htBVLs) were constructed from analogues of the melanocortin peptide ligand ([Nle(4), dPhe(7)]-α-MSH) and the cholecystokinin peptide ligand (CCK-8). Binding of these ligands to cells expressing the human Melanocortin-4 receptor and the Cholecystokinin-2 receptor was analyzed. The MSH(7) and CCK(6) were tethered with linkers of varying rigidity and length, constructed from natural and/or synthetic building blocks. Modeling data suggest that a linker length of 20-50 Å is needed to simultaneously bind these two different G-protein coupled receptors (GPCRs). These ligands exhibited up to 24-fold enhancement in binding affinity to cells that expressed both (bivalent binding), compared to cells with only one (monovalent binding) of the cognate receptors. The htBVLs had up to 50-fold higher affinity than that of a monomeric CCK ligand, i.e., Ac-CCK(6)-NH(2). Cell-surface targeting of these two cell types with labeled heteromultivalent ligand demonstrated high avidity and specificity, thereby validating the receptor combination approach. This ability to noncovalently cross-link heterologous receptors and target individual cells using a receptor combination approach opens up new possibilities for specific cell targeting in vivo for therapy or imaging.

  4. Semiconductor Quantum Dots with Photoresponsive Ligands.

    Science.gov (United States)

    Sansalone, Lorenzo; Tang, Sicheng; Zhang, Yang; Thapaliya, Ek Raj; Raymo, Françisco M; Garcia-Amorós, Jaume

    2016-10-01

    Photochromic or photocaged ligands can be anchored to the outer shell of semiconductor quantum dots in order to control the photophysical properties of these inorganic nanocrystals with optical stimulations. One of the two interconvertible states of the photoresponsive ligands can be designed to accept either an electron or energy from the excited quantum dots and quench their luminescence. Under these conditions, the reversible transformations of photochromic ligands or the irreversible cleavage of photocaged counterparts translates into the possibility to switch luminescence with external control. As an alternative to regulating the photophysics of a quantum dot via the photochemistry of its ligands, the photochemistry of the latter can be controlled by relying on the photophysics of the former. The transfer of excitation energy from a quantum dot to a photocaged ligand populates the excited state of the species adsorbed on the nanocrystal to induce a photochemical reaction. This mechanism, in conjunction with the large two-photon absorption cross section of quantum dots, can be exploited to release nitric oxide or to generate singlet oxygen under near-infrared irradiation. Thus, the combination of semiconductor quantum dots and photoresponsive ligands offers the opportunity to assemble nanostructured constructs with specific functions on the basis of electron or energy transfer processes. The photoswitchable luminescence and ability to photoinduce the release of reactive chemicals, associated with the resulting systems, can be particularly valuable in biomedical research and can, ultimately, lead to the realization of imaging probes for diagnostic applications as well as to therapeutic agents for the treatment of cancer.

  5. Designer TGFβ superfamily ligands with diversified functionality.

    Directory of Open Access Journals (Sweden)

    George P Allendorph

    Full Text Available Transforming Growth Factor--beta (TGFβ superfamily ligands, including Activins, Growth and Differentiation Factors (GDFs, and Bone Morphogenetic Proteins (BMPs, are excellent targets for protein-based therapeutics because of their pervasiveness in numerous developmental and cellular processes. We developed a strategy termed RASCH (Random Assembly of Segmental Chimera and Heteromer, to engineer chemically-refoldable TGFβ superfamily ligands with unique signaling properties. One of these engineered ligands, AB208, created from Activin-βA and BMP-2 sequences, exhibits the refolding characteristics of BMP-2 while possessing Activin-like signaling attributes. Further, we find several additional ligands, AB204, AB211, and AB215, which initiate the intracellular Smad1-mediated signaling pathways more strongly than BMP-2 but show no sensitivity to the natural BMP antagonist Noggin unlike natural BMP-2. In another design, incorporation of a short N-terminal segment from BMP-2 was sufficient to enable chemical refolding of BMP-9, without which was never produced nor refolded. Our studies show that the RASCH strategy enables us to expand the functional repertoire of TGFβ superfamily ligands through development of novel chimeric TGFβ ligands with diverse biological and clinical values.

  6. LigandRFs: random forest ensemble to identify ligand-binding residues from sequence information alone

    KAUST Repository

    Chen, Peng

    2014-12-03

    Background Protein-ligand binding is important for some proteins to perform their functions. Protein-ligand binding sites are the residues of proteins that physically bind to ligands. Despite of the recent advances in computational prediction for protein-ligand binding sites, the state-of-the-art methods search for similar, known structures of the query and predict the binding sites based on the solved structures. However, such structural information is not commonly available. Results In this paper, we propose a sequence-based approach to identify protein-ligand binding residues. We propose a combination technique to reduce the effects of different sliding residue windows in the process of encoding input feature vectors. Moreover, due to the highly imbalanced samples between the ligand-binding sites and non ligand-binding sites, we construct several balanced data sets, for each of which a random forest (RF)-based classifier is trained. The ensemble of these RF classifiers forms a sequence-based protein-ligand binding site predictor. Conclusions Experimental results on CASP9 and CASP8 data sets demonstrate that our method compares favorably with the state-of-the-art protein-ligand binding site prediction methods.

  7. An Experiment Illustrating the Change in Ligand p"K"[subscript a] upon Protein Binding

    Science.gov (United States)

    Chenprakhon, Pirom; Panijpan, Bhinyo; Chaiyen, Pimchai

    2012-01-01

    The modulation of ligand p"K"[subscript a] due to its surrounding environment is a crucial feature that controls many biological phenomena. For example, the shift in the p"K"[subscript a] of substrates or catalytic residues at enzyme active sites upon substrate binding often triggers and controls enzymatic reactions. In this work, we developed an…

  8. Synthesis and characterization of mixed ligand chiral nanoclusters

    KAUST Repository

    Guven, Zekiye P.

    2016-06-22

    Chiral mixed ligand silver nanoclusters were synthesized in the presence of a chiral and an achiral ligand. While the chiral ligand led mostly to the formation of nanoparticles, the presence of the achiral ligand drastically increased the yield of nanoclusters with enhanced chiral properties. © 2016 The Royal Society of Chemistry.

  9. Synthesis and characterization of mixed ligand chiral nanoclusters

    KAUST Repository

    Guven, Zekiye P.; Ustbas, Burcin; Harkness, Kellen M.; Coskun, Hikmet; Joshi, Chakra Prasad; Besong, Tabot M.D.; Stellacci, Francesco; Bakr, Osman; Akbulut, Ozge

    2016-01-01

    Chiral mixed ligand silver nanoclusters were synthesized in the presence of a chiral and an achiral ligand. While the chiral ligand led mostly to the formation of nanoparticles, the presence of the achiral ligand drastically increased the yield of nanoclusters with enhanced chiral properties. © 2016 The Royal Society of Chemistry.

  10. Impact of protein and ligand impurities on ITC-derived protein-ligand thermodynamics.

    Science.gov (United States)

    Grüner, Stefan; Neeb, Manuel; Barandun, Luzi Jakob; Sielaff, Frank; Hohn, Christoph; Kojima, Shun; Steinmetzer, Torsten; Diederich, François; Klebe, Gerhard

    2014-09-01

    The thermodynamic characterization of protein-ligand interactions by isothermal titration calorimetry (ITC) is a powerful tool in drug design, giving valuable insight into the interaction driving forces. ITC is thought to require protein and ligand solutions of high quality, meaning both the absence of contaminants as well as accurately determined concentrations. Ligands synthesized to deviating purity and protein of different pureness were titrated by ITC. Data curation was attempted also considering information from analytical techniques to correct stoichiometry. We used trypsin and tRNA-guanine transglycosylase (TGT), together with high affinity ligands to investigate the effect of errors in protein concentration as well as the impact of ligand impurities on the apparent thermodynamics. We found that errors in protein concentration did not change the thermodynamic properties obtained significantly. However, most ligand impurities led to pronounced changes in binding enthalpy. If protein binding of the respective impurity is not expected, the actual ligand concentration was corrected for and the thus revised data compared to thermodynamic properties obtained with the respective pure ligand. Even in these cases, we observed differences in binding enthalpy of about 4kJ⋅mol(-1), which is considered significant. Our results indicate that ligand purity is the critical parameter to monitor if accurate thermodynamic data of a protein-ligand complex are to be recorded. Furthermore, artificially changing fitting parameters to obtain a sound interaction stoichiometry in the presence of uncharacterized ligand impurities may lead to thermodynamic parameters significantly deviating from the accurate thermodynamic signature. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. New functionalized β-diketiminate ligands and f elements

    International Nuclear Information System (INIS)

    Dulong, Florian

    2013-01-01

    β-diketiminate ligands have received increased interest in coordination chemistry, especially for homogeneous catalysis. Their successful applications arise from an easy and fine tuning of the ligand electronic and geometric properties. However, these modifications are limited to the introduction of neutral donors (ethers or amines), on the nitrogen substituents of the β-diketiminate skeleton. The main focus of this research project is to overcome this limitation by synthesizing new β-diketiminate ligands functionalized by one or two anionic aryl-oxide groups, and to study their coordination chemistry with lanthanide and actinide ions. Access to these species relies on a fine understanding of the mechanism underlying their formation, and the sensitivity of the β-di-iminium skeleton towards nucleophiles (phenols) has been identified as the limiting side reaction in the synthetic route. Addition of reactants in well defined order allowed the formation of two new N-aryl-oxy-β-diketiminate dianions on a multi-gram scale. The two ligands differ by their steric bulk and exhibit different coordination behaviors towards lanthanides and actinide ions, which were rationalized on geometric considerations. The reactivity of three of these new complexes has been investigated. A Ce(III) N-aryl-oxy-β-diketiminate complex exhibits interesting reduction properties, due to the shift of its oxidation potential to negative values by its coordination environment. A Th(IV) complex presents a vacant coordination site, which has been probed with different Lewis bases, emphasizing two spatial arrangements ruled by inter-ligand repulsion. It has been compared to its U(IV) analogue, which can be oxidized to a rare terminal mono-oxo uranium(VI) species. The latter was reversibly reduced to its U(V) and U(IV) derivatives, creating the first series of terminal mono-oxo uranium complexes with three successive oxidation states. These compounds represent an opportunity to better understand

  12. Expression of nociceptive ligands in canine osteosarcoma.

    Science.gov (United States)

    Shor, S; Fadl-Alla, B A; Pondenis, H C; Zhang, X; Wycislo, K L; Lezmi, S; Fan, T M

    2015-01-01

    Canine osteosarcoma (OS) is associated with localized pain as a result of tissue injury from tumor infiltration and peritumoral inflammation. Malignant bone pain is caused by stimulation of peripheral pain receptors, termed nociceptors, which reside in the localized tumor microenvironment, including the periosteal and intramedullary bone cavities. Several nociceptive ligands have been determined to participate directly or indirectly in generating bone pain associated with diverse skeletal abnormalities. Canine OS cells actively produce nociceptive ligands with the capacity to directly or indirectly activate peripheral pain receptors residing in the bone tumor microenvironment. Ten dogs with appendicular OS. Expression of nerve growth factor, endothelin-1, and microsomal prostaglandin E synthase-1 was characterized in OS cell lines and naturally occurring OS samples. In 10 dogs with OS, circulating concentrations of nociceptive ligands were quantified and correlated with subjective pain scores and tumor volume in patients treated with standardized palliative therapies. Canine OS cells express and secrete nerve growth factor, endothelin-1, and prostaglandin E2. Naturally occurring OS samples uniformly express nociceptive ligands. In a subset of OS-bearing dogs, circulating nociceptive ligand concentrations were detectable but failed to correlate with pain status. Localized foci of nerve terminal proliferation were identified in a minority of primary bone tumor samples. Canine OS cells express nociceptive ligands, potentially permitting active participation of OS cells in the generation of malignant bone pain. Specific inhibitors of nociceptive ligand signaling pathways might improve pain control in dogs with OS. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

  13. Immobilisation of ligands by radio-derivatized polymers; Immobilisering av ligander med radioderiverte polymerer

    Energy Technology Data Exchange (ETDEWEB)

    Varga, J.M.; Fritsch, P.

    1995-01-30

    The invention relates to radio-derivatized polymers and a method of producing them by contacting non-polymerizable conjugands with radiolysable polymers in the presence of irradiation. The resulting radio-derivatized polymers can be further linked with ligand of organic or inorganic nature to immobilize such ligands. 2 figs., 5 tabs.

  14. A General Ligand Design for Gold Catalysis allowing Ligand-Directed Anti Nucleophilic Attack of Alkynes

    Science.gov (United States)

    Wang, Yanzhao; Wang, Zhixun; Li, Yuxue; Wu, Gongde; Cao, Zheng; Zhang, Liming

    2014-01-01

    Most homogenous gold catalyses demand ≥0.5 mol % catalyst loading. Due to the high cost of gold, these reactions are unlikely to be applicable in medium or large scale applications. Here we disclose a novel ligand design based on the privileged biphenyl-2-phosphine framework that offers a potentially general approach to dramatically lowering catalyst loading. In this design, an amide group at the 3’ position of the ligand framework directs and promotes nucleophilic attack at the ligand gold complex-activated alkyne, which is unprecedented in homogeneous gold catalysis considering the spatial challenge of using ligand to reach antiapproaching nucleophile in a linear P-Au-alkyne centroid structure. With such a ligand, the gold(I) complex becomes highly efficient in catalyzing acid addition to alkynes, with a turnover number up to 99,000. Density functional theory calculations support the role of the amide moiety in directing the attack of carboxylic acid via hydrogen bonding. PMID:24704803

  15. A new class of PN3-pincer ligands for metal–ligand cooperative catalysis

    KAUST Repository

    Li, Huaifeng

    2014-12-01

    Work on a new class of PN3-pincer ligands for metal-ligand cooperative catalysis is reviewed. While the field of the pyridine-based PN3-transition metal pincer complexes is still relatively young, many important applications of these complexes have already emerged. In several cases, the PN3-pincer complexes for metal-ligand cooperative catalysis result in significantly improved or unprecedented activities. The synthesis and coordination chemistry of PN3-pincer ligands are briefly summarized first to cover the synthetic routes for their preparation, followed by a focus review on their applications in catalysis. A specific emphasis is placed on the later section about the role of PN3-pincer ligands\\' dearomatization-rearomatization steps during the catalytic cycles. The mechanistic insights from density functional theory (DFT) calculations are also discussed.

  16. A new class of PN3-pincer ligands for metal–ligand cooperative catalysis

    KAUST Repository

    Li, Huaifeng; Zheng, Bin; Huang, Kuo-Wei

    2014-01-01

    Work on a new class of PN3-pincer ligands for metal-ligand cooperative catalysis is reviewed. While the field of the pyridine-based PN3-transition metal pincer complexes is still relatively young, many important applications of these complexes have already emerged. In several cases, the PN3-pincer complexes for metal-ligand cooperative catalysis result in significantly improved or unprecedented activities. The synthesis and coordination chemistry of PN3-pincer ligands are briefly summarized first to cover the synthetic routes for their preparation, followed by a focus review on their applications in catalysis. A specific emphasis is placed on the later section about the role of PN3-pincer ligands' dearomatization-rearomatization steps during the catalytic cycles. The mechanistic insights from density functional theory (DFT) calculations are also discussed.

  17. Effects of PPARγ ligands on vascular tone.

    Science.gov (United States)

    Salomone, Salvatore; Drago, Filippo

    2012-06-01

    Peroxisome Proliferator-Activated Receptor γ (PPARγ), originally described as a transcription factor for genes of carbohydrate and lipid metabolism, has been more recently studied in the context of cardiovascular pathophysiology. Here, we review the available data on PPARγ ligands as modulator of vascular tone. PPARγ ligands include: thiazolidinediones (used in the treatment of type 2 diabetes mellitus), glitazars (bind and activate both PPARγ and PPARα), and other experimental drugs (still in development) that exploit the chemistry of thiazolidinediones as a scaffold for PPARγ-independent pharmacological properties. In this review, we examine both short (mostly from in vitro data)- and long (mostly from in vivo data)-term effects of PPARγ ligands that extend from PPARγ-independent vascular effects to PPARγ-dependent gene expression. Because endothelium is a master regulator of vascular tone, we have attempted to differentiate between endothelium-dependent and endothelium-independent effects of PPARγ ligands. Based on available data, we conclude that PPARγ ligands appear to influence vascular tone in different experimental paradigms, most often in terms of vasodilatation (potentially increasing blood flow to some tissues). These effects on vascular tone, although potentially beneficial, must be weighed against specific cardiovascular warnings that may apply to some drugs, such as rosiglitazone.

  18. LIBRA: LIgand Binding site Recognition Application.

    Science.gov (United States)

    Hung, Le Viet; Caprari, Silvia; Bizai, Massimiliano; Toti, Daniele; Polticelli, Fabio

    2015-12-15

    In recent years, structural genomics and ab initio molecular modeling activities are leading to the availability of a large number of structural models of proteins whose biochemical function is not known. The aim of this study was the development of a novel software tool that, given a protein's structural model, predicts the presence and identity of active sites and/or ligand binding sites. The algorithm implemented by ligand binding site recognition application (LIBRA) is based on a graph theory approach to find the largest subset of similar residues between an input protein and a collection of known functional sites. The algorithm makes use of two predefined databases for active sites and ligand binding sites, respectively, derived from the Catalytic Site Atlas and the Protein Data Bank. Tests indicate that LIBRA is able to identify the correct binding/active site in 90% of the cases analyzed, 90% of which feature the identified site as ranking first. As far as ligand binding site recognition is concerned, LIBRA outperforms other structure-based ligand binding sites detection tools with which it has been compared. The application, developed in Java SE 7 with a Swing GUI embedding a JMol applet, can be run on any OS equipped with a suitable Java Virtual Machine (JVM), and is available at the following URL: http://www.computationalbiology.it/software/LIBRAv1.zip. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Dockomatic - automated ligand creation and docking.

    Science.gov (United States)

    Bullock, Casey W; Jacob, Reed B; McDougal, Owen M; Hampikian, Greg; Andersen, Tim

    2010-11-08

    The application of computational modeling to rationally design drugs and characterize macro biomolecular receptors has proven increasingly useful due to the accessibility of computing clusters and clouds. AutoDock is a well-known and powerful software program used to model ligand to receptor binding interactions. In its current version, AutoDock requires significant amounts of user time to setup and run jobs, and collect results. This paper presents DockoMatic, a user friendly Graphical User Interface (GUI) application that eases and automates the creation and management of AutoDock jobs for high throughput screening of ligand to receptor interactions. DockoMatic allows the user to invoke and manage AutoDock jobs on a single computer or cluster, including jobs for evaluating secondary ligand interactions. It also automates the process of collecting, summarizing, and viewing results. In addition, DockoMatic automates creation of peptide ligand .pdb files from strings of single-letter amino acid abbreviations. DockoMatic significantly reduces the complexity of managing multiple AutoDock jobs by facilitating ligand and AutoDock job creation and management.

  20. Dockomatic - automated ligand creation and docking

    Directory of Open Access Journals (Sweden)

    Hampikian Greg

    2010-11-01

    Full Text Available Abstract Background The application of computational modeling to rationally design drugs and characterize macro biomolecular receptors has proven increasingly useful due to the accessibility of computing clusters and clouds. AutoDock is a well-known and powerful software program used to model ligand to receptor binding interactions. In its current version, AutoDock requires significant amounts of user time to setup and run jobs, and collect results. This paper presents DockoMatic, a user friendly Graphical User Interface (GUI application that eases and automates the creation and management of AutoDock jobs for high throughput screening of ligand to receptor interactions. Results DockoMatic allows the user to invoke and manage AutoDock jobs on a single computer or cluster, including jobs for evaluating secondary ligand interactions. It also automates the process of collecting, summarizing, and viewing results. In addition, DockoMatic automates creation of peptide ligand .pdb files from strings of single-letter amino acid abbreviations. Conclusions DockoMatic significantly reduces the complexity of managing multiple AutoDock jobs by facilitating ligand and AutoDock job creation and management.

  1. Ligand identification using electron-density map correlations

    International Nuclear Information System (INIS)

    Terwilliger, Thomas C.; Adams, Paul D.; Moriarty, Nigel W.; Cohn, Judith D.

    2007-01-01

    An automated ligand-fitting procedure is applied to (F o − F c )exp(iϕ c ) difference density for 200 commonly found ligands from macromolecular structures in the Protein Data Bank to identify ligands from density maps. A procedure for the identification of ligands bound in crystal structures of macromolecules is described. Two characteristics of the density corresponding to a ligand are used in the identification procedure. One is the correlation of the ligand density with each of a set of test ligands after optimization of the fit of that ligand to the density. The other is the correlation of a fingerprint of the density with the fingerprint of model density for each possible ligand. The fingerprints consist of an ordered list of correlations of each the test ligands with the density. The two characteristics are scored using a Z-score approach in which the correlations are normalized to the mean and standard deviation of correlations found for a variety of mismatched ligand-density pairs, so that the Z scores are related to the probability of observing a particular value of the correlation by chance. The procedure was tested with a set of 200 of the most commonly found ligands in the Protein Data Bank, collectively representing 57% of all ligands in the Protein Data Bank. Using a combination of these two characteristics of ligand density, ranked lists of ligand identifications were made for representative (F o − F c )exp(iϕ c ) difference density from entries in the Protein Data Bank. In 48% of the 200 cases, the correct ligand was at the top of the ranked list of ligands. This approach may be useful in identification of unknown ligands in new macromolecular structures as well as in the identification of which ligands in a mixture have bound to a macromolecule

  2. Sorção e dessorção do imazaquin em solos com diferentes características granulométricas, químicas e mineralógicas Imazaquin sorption and desorption in soils with different mineralogical, physical and chemical characteristics

    Directory of Open Access Journals (Sweden)

    Robson Rolland Monticelli Barizon

    2005-10-01

    Full Text Available O presente estudo teve o objetivo de avaliar a sorção e dessorção do imazaquin em solos com diferentes características granulométricas, químicas e mineralógicas por meio de isotermas e estudos de cinética e, assim, quantificar a histerese no processo de sorção-dessorção. Os solos utilizados foram classificados como Latossolo Vermelho distroférrico (LVdf, Latossolo Vermelho-Amarelo (LVA e Neossolo Quartzarênico (RQ. Os solos foram secos ao ar e peneirados em malha de 2 mm, sendo então procedida à caracterização dessas amostras. A molécula radiomarcada com 14C utilizada foi o imazaquin, herbicida do grupo das imidazolinonas. A radioatividade foi determinada por espectrometria de cintilação líquida. Os ensaios foram realizados em sala climatizada (25 ± 2 °C. Nas isotermas de sorção, foram utilizadas cinco concentrações do imazaquin (0,67; 1,34; 2,68; 5,36; 10,72 µmol L-1, sendo os resultados ajustados à equação de Freundlich, obtendo, assim, os parâmetros de sorção. Na seqüência, foram realizadas quatro extrações com solução 0,005 mol L-1 de CaCl2, determinando-se os parâmetros de dessorção de forma similar à sorção. No ensaio de cinética de sorção, foi determinada a quantidade sorvida de imazaquin, a partir da adição de solução de 2,99 µmol L-1 do imazaquin, em períodos preestabelecidos (0; 0,5; 1; 3; 6; 12; 24 e 48 h, após a aplicação do imazaquin, com os resultados sendo ajustados à equação de Elovich. De maneira geral, o imazaquin apresentou baixa sorção para os três solos, com os maiores coeficientes de sorção nos solos com maior teor de argila e CO. Os coeficientes de dessorção foram maiores que os coeficientes de sorção, demonstrando a ocorrência de histerese. A cinética de sorção mostrou que o imazaquin foi sorvido em duas etapas: uma rápida, que apresentou a maior fração sorvida, e outra lenta. A aplicação da Lei de Fick aos dados experimentais do ensaio de

  3. Ligand sphere conversions in terminal carbide complexes

    DEFF Research Database (Denmark)

    Morsing, Thorbjørn Juul; Reinholdt, Anders; Sauer, Stephan P. A.

    2016-01-01

    Metathesis is introduced as a preparative route to terminal carbide complexes. The chloride ligands of the terminal carbide complex [RuC(Cl)2(PCy3)2] (RuC) can be exchanged, paving the way for a systematic variation of the ligand sphere. A series of substituted complexes, including the first...... example of a cationic terminal carbide complex, [RuC(Cl)(CH3CN)(PCy3)2]+, is described and characterized by NMR, MS, X-ray crystallography, and computational studies. The experimentally observed irregular variation of the carbide 13C chemical shift is shown to be accurately reproduced by DFT, which also...... demonstrates that details of the coordination geometry affect the carbide chemical shift equally as much as variations in the nature of the auxiliary ligands. Furthermore, the kinetics of formation of the sqaure pyramidal dicyano complex, trans-[RuC(CN)2(PCy3)2], from RuC has been examined and the reaction...

  4. Characteristic molecular vibrations of adenosine receptor ligands.

    Science.gov (United States)

    Chee, Hyun Keun; Yang, Jin-San; Joung, Je-Gun; Zhang, Byoung-Tak; Oh, S June

    2015-02-13

    Although the regulation of membrane receptor activation is known to be crucial for molecular signal transduction, the molecular mechanism underlying receptor activation is not fully elucidated. Here we study the physicochemical nature of membrane receptor behavior by investigating the characteristic molecular vibrations of receptor ligands using computational chemistry and informatics methods. By using information gain, t-tests, and support vector machines, we have identified highly informative features of adenosine receptor (AdoR) ligand and corresponding functional amino acid residues such as Asn (6.55) of AdoR that has informative significance and is indispensable for ligand recognition of AdoRs. These findings may provide new perspectives and insights into the fundamental mechanism of class A G protein-coupled receptor activation. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  5. Supramolecular architectures constructed using angular bipyridyl ligands

    International Nuclear Information System (INIS)

    Barnett, Sarah Ann

    2003-01-01

    This work details the synthesis and characterization of a series of coordination frameworks that are formed using bidentate angular N-donor ligands. Pyrimidine was reacted with metal(ll) nitrate salts. Reactions using Cd(NO 3 ) 2 receive particular focus and the analogous reactions using the linear ligand, pyrazine, were studied for comparison. In all cases, two-dimensional coordination networks were prepared. Structural diversity is observed for the Cd(ll) centres including metal-nitrate bridging. In contrast, first row transition metal nitrates form isostructural one-dimensional chains with only the bridging N-donor ligands generating polymeric propagation. The angular ligand, 2,4-bis(4-pyridyl)-1,3,5-triazine (dpt), was reacted with Cd(NO 3 ) 2 and Zn(NO 3 ) 2 . Whereas Zn(NO 3 ) 2 compounds exhibit solvent mediated polymorphism, a range of structures were obtained for the reactions with Cd(NO 3 ) 2 , including the first example of a doubly parallel interpenetrated 4.8 2 net. 4,7-phenanthroline, was reacted with various metal(ll) nitrates as well as cobalt(ll) and copper(ll) halides. The ability of 4,7-phenanthroline to act as both a N-donor ligand and a hydrogen bond acceptor has been discussed. Reactions of CuSCN with pyrimidine yield an unusual three-dimensional structure in which polymeric propagation is not a result of ligand bridging. The reaction of CuSCN with dpt yielded structural supramolecular isomers. (author)

  6. Strong Ligand-Protein Interactions Derived from Diffuse Ligand Interactions with Loose Binding Sites.

    Science.gov (United States)

    Marsh, Lorraine

    2015-01-01

    Many systems in biology rely on binding of ligands to target proteins in a single high-affinity conformation with a favorable ΔG. Alternatively, interactions of ligands with protein regions that allow diffuse binding, distributed over multiple sites and conformations, can exhibit favorable ΔG because of their higher entropy. Diffuse binding may be biologically important for multidrug transporters and carrier proteins. A fine-grained computational method for numerical integration of total binding ΔG arising from diffuse regional interaction of a ligand in multiple conformations using a Markov Chain Monte Carlo (MCMC) approach is presented. This method yields a metric that quantifies the influence on overall ligand affinity of ligand binding to multiple, distinct sites within a protein binding region. This metric is essentially a measure of dispersion in equilibrium ligand binding and depends on both the number of potential sites of interaction and the distribution of their individual predicted affinities. Analysis of test cases indicates that, for some ligand/protein pairs involving transporters and carrier proteins, diffuse binding contributes greatly to total affinity, whereas in other cases the influence is modest. This approach may be useful for studying situations where "nonspecific" interactions contribute to biological function.

  7. Study on the optical properties of CdSe QDs with different ligands in specific matrix

    International Nuclear Information System (INIS)

    Lin Wei; Zou Wei; Du Zhongjie; Li Hangquan; Zhang Chen

    2013-01-01

    Different ligand structures of CdSe quantum dots were designed and synthesized for the specific matrix and the effect of the ligands on the photoluminescence and optical properties were further investigated. Ligand exchange reaction was used to synthesize thioglycolic acid-capped CdSe QDs and the process was characterized by FT-IR and titration. The influence of environmental pH value and storing time on the properties of thioglycolic acid-capped CdSe QDs in aqueous solution were studied by absorption and photoluminescence spectra. It was found that alkaline environment was more beneficial for the application of CdSe QDs. Therefore, the amino ligands with different molecular weight were grafted onto CdSe QDs for improving the compatibility with epoxy matrix and then amino-capped CdSe QDs/epoxy nanocomposites were fabricated. The morphologies and properties of the nanocomposites were characterized by DLS, HR-TEM, UV–Vis spectra, and photoluminescence spectra. As a result, amino ligands with short-molecular chain-capped CdSe QDs/epoxy nanocomposites exhibited good dispersion, high transparency and photoluminescence, and would be suitable for potential application in light-emitting diode device.

  8. Interaction of calreticulin with CD40 ligand, TRAIL and Fas ligand

    DEFF Research Database (Denmark)

    Duus, K; Pagh, R T; Holmskov, U

    2007-01-01

    is utilized by many other functionally diverse molecules and in this work the interaction of calreticulin with C1q and structurally similar molecules was investigated. In addition to C1q and MBL, CD40 ligand (CD40L), tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL) were...... found to bind calreticulin strongly. A low level or no binding was observed for adiponectin, tumour necrosis factor-alpha (TNF-alpha), CD30L, surfactant protein-A and -D and collagen VIII. The interaction with calreticulin required a conformational change in CD40L, TRAIL and FasL and showed the same...

  9. Structural characterization of natural nickel and copper binding ligands along the US GEOTRACES Eastern Pacific Zonal transect

    Directory of Open Access Journals (Sweden)

    Rene M Boiteau

    2016-11-01

    Full Text Available Organic ligands form strong complexes with many trace elements in seawater. Various metals can compete for the same ligand chelation sites, and the final speciation of bound metals is determined by relative binding affinities, concentrations of binding sites, uncomplexed metal concentrations, and association/dissociation kinetics. Different ligands have a wide range of metal affinities and specificities. However, the chemical composition of these ligands in the marine environment remains poorly constrained, which has hindered progress in modeling marine metal speciation. In this study, we detected and characterized natural ligands that bind copper (Cu and nickel (Ni in the eastern South Pacific Ocean with liquid chromatography tandem inductively coupled plasma mass spectrometry (LC-ICPMS, and high resolution electrospray ionization mass spectrometry (ESIMS. Dissolved Cu, Ni, and ligand concentrations were highest near the coast. Chromatographically unresolved polar compounds dominated ligands isolated near the coast by solid phase extraction. Offshore, metal and ligand concentrations decreased, but several new ligands appeared. One major ligand was detected that bound both Cu2+ and Ni2+. Based on accurate mass and fragmentation measurements, this compound has a molecular formula of C20H21N4O8S2 + M+ (M = metal isotope and contains several azole-like metal binding groups. Additional lipophilic Ni complexes were also present only in oligotrophic waters, with masses of 649, 698, and 712 m/z (corresponding to the 58Ni metal complex. Molecular formulae of C32H54N3O6S2Ni+ and C33H56N3O6S2Ni+ were determined for two of these compounds. Addition of Cu and Ni to the samples also revealed the presence of additional compounds that can bind both Ni and Cu. Although these specific compounds represent a small fraction of the total dissolved Cu and Ni pool, they highlight the compositional diversity and spatial heterogeneity of marine Ni and Cu ligands, as

  10. Ligand iron catalysts for selective hydrogenation

    Science.gov (United States)

    Casey, Charles P.; Guan, Hairong

    2010-11-16

    Disclosed are iron ligand catalysts for selective hydrogenation of aldehydes, ketones and imines. A catalyst such as dicarbonyl iron hydride hydroxycyclopentadiene) complex uses the OH on the five member ring and hydrogen linked to the iron to facilitate hydrogenation reactions, particularly in the presence of hydrogen gas.

  11. Programmed Death-Ligand 1 Immunohistochemistry Testing

    DEFF Research Database (Denmark)

    Büttner, Reinhard; Gosney, John R; Skov, Birgit Guldhammer

    2017-01-01

    Purpose Three programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors are currently approved for treatment of non-small-cell lung cancer (NSCLC). Treatment with pembrolizumab in NSCLC requires PD-L1 immunohistochemistry (IHC) testing. Nivolumab and atezolizumab are approved without PD-L1...

  12. Versatile phosphite ligands based on silsesquioxane backbones

    NARCIS (Netherlands)

    van der Vlugt, JI; Ackerstaff, J; Dijkstra, TW; Mills, AM; Kooijman, H; Spek, AL; Meetsma, A; Abbenhuis, HCL; Vogt, D

    Silsesquioxanes are employed as ligand backbones for the synthesis of novel phosphite compounds with 3,3'-5,5'-tetrakis(tert-butyl)-2,2'-di-oxa-1,1'-biphenyl substituents. Both mono- and bidentate phosphites are prepared in good yields. Two types of silsesquioxanes are employed as starting

  13. Ammonia formation by metal-ligand cooperative hydrogenolysis of a nitrido ligand

    Science.gov (United States)

    Askevold, Bjorn; Nieto, Jorge Torres; Tussupbayev, Samat; Diefenbach, Martin; Herdtweck, Eberhardt; Holthausen, Max C.; Schneider, Sven

    2011-07-01

    Bioinspired hydrogenation of N2 to ammonia at ambient conditions by stepwise nitrogen protonation/reduction with metal complexes in solution has experienced remarkable progress. In contrast, the highly desirable direct hydrogenation with H2 remains difficult. In analogy to the heterogeneously catalysed Haber-Bosch process, such a reaction is conceivable via metal-centred N2 splitting and unprecedented hydrogenolysis of the nitrido ligands to ammonia. We report the synthesis of a ruthenium(IV) nitrido complex. The high nucleophilicity of the nitrido ligand is demonstrated by unusual N-C coupling with π-acidic CO. Furthermore, the terminal nitrido ligand undergoes facile hydrogenolysis with H2 at ambient conditions to produce ammonia in high yield. Kinetic and quantum chemical examinations of this reaction suggest cooperative behaviour of a phosphorus-nitrogen-phosphorus pincer ligand in rate-determining heterolytic hydrogen splitting.

  14. Dynamic ligand-based pharmacophore modeling and virtual ...

    Indian Academy of Sciences (India)

    Five ligand-based pharmacophore models were generated from 40 different .... the Phase module of the Schrodinger program.35 Each model consisted of six types of ... ligand preparation included the OPLS_2005 force field and to retain the ...

  15. Substrate coated with receptor and labelled ligand for assays

    International Nuclear Information System (INIS)

    1980-01-01

    Improvements in the procedures for assaying ligands are described. The assay consists of a polystyrene tube on which receptors are present for both the ligand to be assayed and a radioactively labelled form of the ligand. The receptors on the bottom portion of the tube are also coated with labelled ligands, thus eliminating the necessity for separate addition of the labelled ligand and sample during an assay. Examples of ligands to which this method is applicable include polypeptides, nucleotides, nucleosides and proteins. Specific examples are given in which the ligand to be assayed is digoxin, the labelled form of the ligand is 3-0-succinyl digoxyigenin tyrosine ( 125 I) and the receptor is digoxin antibody. (U.K.)

  16. Role of ligand-ligand vs. core-core interactions in gold nanoclusters.

    Science.gov (United States)

    Milowska, Karolina Z; Stolarczyk, Jacek K

    2016-05-14

    The controlled assembly of ligand-coated gold nanoclusters (NCs) into larger structures paves the way for new applications ranging from electronics to nanomedicine. Here, we demonstrate through rigorous density functional theory (DFT) calculations employing novel functionals accounting for van der Waals forces that the ligand-ligand interactions determine whether stable assemblies can be formed. The study of NCs with different core sizes, symmetry forms, ligand lengths, mutual crystal orientations, and in the presence of a solvent suggests that core-to-core van der Waals interactions play a lesser role in the assembly. The dominant interactions originate from combination of steric effects, augmented by ligand bundling on NC facets, and related to them changes in electronic properties induced by neighbouring NCs. We also show that, in contrast to standard colloidal theory approach, DFT correctly reproduces the surprising experimental trends in the strength of the inter-particle interaction observed when varying the length of the ligands. The results underpin the importance of understanding NC interactions in designing gold NCs for a specific function.

  17. Mutual control of axial and equatorial ligands: model studies with [Ni]-bacteriochlorophyll-a.

    Science.gov (United States)

    Yerushalmi, Roie; Noy, Dror; Baldridge, Kim K; Scherz, Avigdor

    2002-07-17

    Modification of the metal's electronic environment by ligand association and dissociation in metalloenzymes is considered cardinal to their catalytic activity. We have recently presented a novel system that utilizes the bacteriochlorophyll (BChl) macrocycle as a ligand and reporter. This system allows for charge mobilization in the equatorial plane and experimental estimate of changes in the electronic charge density around the metal with no modification of the metal's chemical environment. The unique spectroscopy, electrochemistry and coordination chemistry of [Ni]-bacteriochlorophyll ([Ni]-BChl) enable us to follow directly fine details and steps involved in the function of the metal redox center. This approach is utilized here whereby electro-chemical reduction of [Ni]-BChl to the monoanion [Ni]-BChl(-) results in reversible dissociation of biologically relevant axial ligands. Similar ligand dissociation was previously detected upon photoexcitation of [Ni]-BChl (Musewald, C.; Hartwich, G.; Lossau, H.; Gilch, P.; Pollinger-Dammer, F.; Scheer, H.; Michel-Beyerle, M. E. J. Phys. Chem. B 1999, 103, 7055-7060 and Noy, D.; Yerushalmi, R.; Brumfeld, V.; Ashur, I.; Baldridge, K. K.; Scheer, H.; Scherz, A. J. Am. Chem. Soc. 2000, 122, 3937-3944). The electrochemical measurements and quantum mechanical (QM) calculations performed here for the neutral, singly reduced, monoligated, and singly reduced, monoligated [Ni]-BChl suggest the following: (a) Electroreduction, although resulting in a pi anion [Ni]-BChl(-) radical, causes electron density migration to the [Ni]-BChl core. (b) Reduction of nonligated [Ni]-BChl does not change the macrocycle conformation, whereas axial ligation results in a dramatic expansion of the metal core and a flattening of the highly ruffled macrocycle conformation. (c) In both the monoanion and singly excited [Ni]-BChl ([Ni]-BChl*), the frontier singly occupied molecular orbital (SOMO) has a small but nonnegligible metal character. Finally, (d

  18. AutoSite: an automated approach for pseudo-ligands prediction—from ligand-binding sites identification to predicting key ligand atoms

    Science.gov (United States)

    Ravindranath, Pradeep Anand; Sanner, Michel F.

    2016-01-01

    Motivation: The identification of ligand-binding sites from a protein structure facilitates computational drug design and optimization, and protein function assignment. We introduce AutoSite: an efficient software tool for identifying ligand-binding sites and predicting pseudo ligand corresponding to each binding site identified. Binding sites are reported as clusters of 3D points called fills in which every point is labelled as hydrophobic or as hydrogen bond donor or acceptor. From these fills AutoSite derives feature points: a set of putative positions of hydrophobic-, and hydrogen-bond forming ligand atoms. Results: We show that AutoSite identifies ligand-binding sites with higher accuracy than other leading methods, and produces fills that better matches the ligand shape and properties, than the fills obtained with a software program with similar capabilities, AutoLigand. In addition, we demonstrate that for the Astex Diverse Set, the feature points identify 79% of hydrophobic ligand atoms, and 81% and 62% of the hydrogen acceptor and donor hydrogen ligand atoms interacting with the receptor, and predict 81.2% of water molecules mediating interactions between ligand and receptor. Finally, we illustrate potential uses of the predicted feature points in the context of lead optimization in drug discovery projects. Availability and Implementation: http://adfr.scripps.edu/AutoDockFR/autosite.html Contact: sanner@scripps.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27354702

  19. A response calculus for immobilized T cell receptor ligands

    DEFF Research Database (Denmark)

    Andersen, P S; Menné, C; Mariuzza, R A

    2001-01-01

    determine the level of T cell activation. When fitted to T cell responses against purified ligands immobilized on plastic surfaces, the 2D-affinity model adequately simulated changes in cellular activation as a result of varying ligand affinity and ligand density. These observations further demonstrated...

  20. Fullerenes as a new type of ligands for transition metals

    International Nuclear Information System (INIS)

    Sokolov, V.I.

    2007-01-01

    Fullerenes are considered as ligands in transition metal π-complexes. The following aspects are discussed: metals able to form π-complexes with fullerenes (Zr, V, Ta, Mo, W, Re, Ru, etc.); haptic numbers; homo- and hetero ligand complexes; ligand compatibility with fullerenes for different metals, including fullerenes with a disturbed structure of conjugation [ru

  1. New pinene-derived pyridines as bidentate chiral ligands

    Czech Academy of Sciences Publication Activity Database

    Malkov, A. V.; Stewart-Liddon, A.; Teplý, Filip; Kobr, L.; Muir, K. W.; Haigh, D.; Kočovský, P.

    2008-01-01

    Roč. 64, č. 18 (2008), s. 4011-4025 ISSN 0040-4020 Institutional research plan: CEZ:AV0Z40550506 Keywords : chiral ligands * transition metal catalysis * asymmetric catalysis * pyridine ligands * oxazoline ligands Subject RIV: CC - Organic Chemistry Impact factor: 2.897, year: 2008

  2. Qualitative study of African-American job satisfaction in a scientific/technical research environment

    Energy Technology Data Exchange (ETDEWEB)

    Krossa, Cheryl Delemos [San Francisco Univ. (United States)

    1996-09-01

    Many studies have been conducted in the area of job satisfaction. Its necessary attributes sor components have been studied, analyzed, validated, standardized, and normed, onpredominantly white male populations. Few of these studies have focused on people of color, specifically African-Americans, and fewer still on those African-Americans working in a high-tech, scientific and research environments. The researchers have defined what is necessary for the current dominent culture`s population, but are their findings applicable and valid for our nation`s other cultures and ethnic groups? Among the conclusions: the subjects felt that there was no real difference in job satisfiers from their white colleagues; however the subjects had the sense of community (African-American) and the need to give back to it. Frustrations included politics, funding, and lack of control.

  3. Sigma-2 receptor ligands QSAR model dataset

    Directory of Open Access Journals (Sweden)

    Antonio Rescifina

    2017-08-01

    Full Text Available The data have been obtained from the Sigma-2 Receptor Selective Ligands Database (S2RSLDB and refined according to the QSAR requirements. These data provide information about a set of 548 Sigma-2 (σ2 receptor ligands selective over Sigma-1 (σ1 receptor. The development of the QSAR model has been undertaken with the use of CORAL software using SMILES, molecular graphs and hybrid descriptors (SMILES and graph together. Data here reported include the regression for σ2 receptor pKi QSAR models. The QSAR model was also employed to predict the σ2 receptor pKi values of the FDA approved drugs that are herewith included.

  4. Metal-ligand cooperative activation of nitriles by a ruthenium complex with a de-aromatized PNN pincer ligand

    NARCIS (Netherlands)

    Eijsink, Linda E; Perdriau, Sébastien C P; de Vries, Johannes G; Otten, Edwin

    2016-01-01

    The pincer complex (PNN)RuH(CO), with a de-aromatized pyridine in the ligand backbone, is shown to react with nitriles in a metal-ligand cooperative manner. This leads to the formation of a series of complexes with new Ru-N(nitrile) and C(ligand)-C(nitrile) bonds. The initial nitrile cycloaddition

  5. Cell surface receptors for signal transduction and ligand transport: a design principles study.

    Directory of Open Access Journals (Sweden)

    Harish Shankaran

    2007-06-01

    Full Text Available Receptors constitute the interface of cells to their external environment. These molecules bind specific ligands involved in multiple processes, such as signal transduction and nutrient transport. Although a variety of cell surface receptors undergo endocytosis, the systems-level design principles that govern the evolution of receptor trafficking dynamics are far from fully understood. We have constructed a generalized mathematical model of receptor-ligand binding and internalization to understand how receptor internalization dynamics encodes receptor function and regulation. A given signaling or transport receptor system represents a particular implementation of this module with a specific set of kinetic parameters. Parametric analysis of the response of receptor systems to ligand inputs reveals that receptor systems can be characterized as being: i avidity-controlled where the response control depends primarily on the extracellular ligand capture efficiency, ii consumption-controlled where the ability to internalize surface-bound ligand is the primary control parameter, and iii dual-sensitivity where both the avidity and consumption parameters are important. We show that the transferrin and low-density lipoprotein receptors are avidity-controlled, the vitellogenin receptor is consumption-controlled, and the epidermal growth factor receptor is a dual-sensitivity receptor. Significantly, we show that ligand-induced endocytosis is a mechanism to enhance the accuracy of signaling receptors rather than merely serving to attenuate signaling. Our analysis reveals that the location of a receptor system in the avidity-consumption parameter space can be used to understand both its function and its regulation.

  6. Multiple ligand-binding modes in bacterial R67 dihydrofolate reductase

    Science.gov (United States)

    Alonso, Hernán; Gillies, Malcolm B.; Cummins, Peter L.; Bliznyuk, Andrey A.; Gready, Jill E.

    2005-03-01

    R67 dihydrofolate reductase (DHFR), a bacterial plasmid-encoded enzyme associated with resistance to the drug trimethoprim, shows neither sequence nor structural homology with the chromosomal DHFR. It presents a highly symmetrical toroidal structure, where four identical monomers contribute to the unique central active-site pore. Two reactants (dihydrofolate, DHF), two cofactors (NADPH) or one of each (R67•DHF•NADPH) can be found simultaneously within the active site, the last one being the reactive ternary complex. As the positioning of the ligands has proven elusive to empirical determination, we addressed the problem from a theoretical perspective. Several potential structures of the ternary complex were generated using the docking programs AutoDock and FlexX. The variability among the final poses, many of which conformed to experimental data, prompted us to perform a comparative scoring analysis and molecular dynamics simulations to assess the stability of the complexes. Analysis of ligand-ligand and ligand-protein interactions along the 4 ns trajectories of eight different structures allowed us to identify important inter-ligand contacts and key protein residues. Our results, combined with published empirical data, clearly suggest that multipe binding modes of the ligands are possible within R67 DHFR. While the pterin ring of DHF and the nicotinamide ring of NADPH assume a stacked endo-conformation at the centre of the pore, probably assisted by V66, Q67 and I68, the tails of the molecules extend towards opposite ends of the cavity, adopting multiple configurations in a solvent rich-environment where hydrogen-bond interactions with K32 and Y69 may play important roles.

  7. EGFR Activation by Spatially Restricted Ligands

    Science.gov (United States)

    2006-06-01

    the level of ligand production, that result in human breast cancer. We have integrated genetic and biochemical methods to study (1) the effects of a...and spindle-B encode components of the RAD52 DNA repair pathway and affect meiosis and patterning in Drosophila oogenesis. Genes Dev 12, 2711-2723...findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision

  8. Selective oxoanion separation using a tripodal ligand

    Energy Technology Data Exchange (ETDEWEB)

    Custelcean, Radu; Moyer, Bruce A.; Rajbanshi, Arbin

    2016-02-16

    The present invention relates to urea-functionalized crystalline capsules self-assembled by sodium or potassium cation coordination and by hydrogen-bonding water bridges to selectively encapsulate tetrahedral divalent oxoanions from highly competitive aqueous alkaline solutions and methods using this system for selective anion separations from industrial solutions. The method involves competitive crystallizations using a tripodal tris(urea) functionalized ligand and, in particular, provides a viable approach to sulfate separation from nuclear wastes.

  9. Targeting Selectins and Their Ligands in Cancer

    Directory of Open Access Journals (Sweden)

    Alessandro eNatoni

    2016-04-01

    Full Text Available Aberrant glycosylation is a hallmark of cancer cells with increased evidence pointing to a role in tumor progression. In particular, aberrant sialylation of glycoproteins and glycolipids have been linked to increased immune cell evasion, drug evasion, drug resistance, tumor invasiveness, and vascular dissemination leading to metastases. Hypersialylation of cancer cells is largely the result of overexpression of sialyltransferases. Humans differentially express twenty different sialyltransferases in a tissue-specific manner, each of which catalyze the attachment of sialic acids via different glycosidic linkages (2-3; 2-6 or 2-8 to the underlying glycan chain. One important mechanism whereby overexpression of sialyltransferases contributes to an enhanced metastatic phenotype is via the generation of selectin ligands. Selectin ligand function requires the expression of sialyl-Lewis X and its structural-isomer sialyl-Lewis A, which are synthesized by the combined action of alpha 1-3-fucosyltransferases, 2-3-sialyltransferases, 1-4-galactosyltranferases, and N-acetyl--glucosaminyltransferases. The α2-3-sialyltransferases ST3Gal4 and ST3Gal6 are critical to the generation of functional E- and P-selectin ligands and overexpression of these sialyltransferases have been linked to increased risk of metastatic disease in solid tumors and poor outcome in multiple myeloma. Thus, targeting selectins and their ligands as well as the enzymes involved in their generation, in particular sialyltransferases, could be beneficial to many cancer patients. Potential strategies include sialyltransferase inhibition and the use of selectin antagonists, such as glycomimetic drugs and antibodies. Here, we review ongoing efforts to optimize the potency and selectivity of sialyltransferase inhibitors, including the potential for targeted delivery approaches, as well as evaluate the potential utility of selectin inhibitors, which are now in early clinical

  10. Sor Juana y la piedra filosofal

    Directory of Open Access Journals (Sweden)

    Dardo Scavino

    2008-07-01

    Full Text Available ...el deseo no satisfecho incrusta en la memoria experiencias imaginarias, apetecidas pero no realizadas, más imborrables que las verdaderasJuan José SaerTimeoEn su Nuevo diccionario enciclopédico de las ciencias del lenguaje Oswald Ducrot y Jean-Marie Schaeffer proponen una breve receta : "Consígase un pollo bien vivo, mátelo, vacíelo, trócelo, métalo en el horno y sírvalo con cebollas." A medida que la receta transcurre, observaban los lingüistas, "el pollo, referente común de los diferente...

  11. Challenges for the development of a biotic ligand model predicting copper toxicity in estuaries and seas

    OpenAIRE

    de Polo, A; Scrimshaw, MD

    2012-01-01

    This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2011 SETAC. An effort is ongoing to develop a biotic ligand model (BLM) that predicts copper (Cu) toxicity in estuarine and marine environments. At present, the BLM accounts for the effects of water chemistry on Cu speciation, but it does not consider the influence of water chemistry on the physiology of the organisms. We discuss how chemistry affects Cu toxicity not only by ...

  12. Synthetic NCAM-derived Ligands of the Fibroblast Growth Factor Receptor

    DEFF Research Database (Denmark)

    Hansen, Stine; Li, Shizhong; Bock, Elisabeth

    2008-01-01

    The neural cell adhesion molecule (NCAM) responds to cues in the external environment and transmits signals to the cell through extracellular and intracellular interactions with a number of other signal transduction molecules. One such NCAM interaction partner is the fibroblast growth factor...... various FN3 module loop regions, have been identified as FGFR ligands. All four peptides activate FGFR and differentially modulate a number of neuronal functions, such as differentiation, survival, and synaptic changes that are important for learning, memory, and neuronal regeneration....

  13. Determination of ligand binding modes in weak protein–ligand complexes using sparse NMR data

    Energy Technology Data Exchange (ETDEWEB)

    Mohanty, Biswaranjan; Williams, Martin L.; Doak, Bradley C.; Vazirani, Mansha; Ilyichova, Olga [Monash University, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences (Australia); Wang, Geqing [La Trobe University, La Trobe Institute for Molecular Bioscience (Australia); Bermel, Wolfgang [Bruker Biospin GmbH (Germany); Simpson, Jamie S.; Chalmers, David K. [Monash University, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences (Australia); King, Glenn F. [The University of Queensland, Institute for Molecular Bioscience (Australia); Mobli, Mehdi, E-mail: m.mobli@uq.edu.au [The University of Queensland, Centre for Advanced Imaging (Australia); Scanlon, Martin J., E-mail: martin.scanlon@monash.edu [Monash University, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences (Australia)

    2016-11-15

    We describe a general approach to determine the binding pose of small molecules in weakly bound protein–ligand complexes by deriving distance constraints between the ligand and methyl groups from all methyl-containing residues of the protein. We demonstrate that using a single sample, which can be prepared without the use of expensive precursors, it is possible to generate high-resolution data rapidly and obtain the resonance assignments of Ile, Leu, Val, Ala and Thr methyl groups using triple resonance scalar correlation data. The same sample may be used to obtain Met {sup ε}CH{sub 3} assignments using NOESY-based methods, although the superior sensitivity of NOESY using [U-{sup 13}C,{sup 15}N]-labeled protein makes the use of this second sample more efficient. We describe a structural model for a weakly binding ligand bound to its target protein, DsbA, derived from intermolecular methyl-to-ligand nuclear Overhauser enhancements, and demonstrate that the ability to assign all methyl resonances in the spectrum is essential to derive an accurate model of the structure. Once the methyl assignments have been obtained, this approach provides a rapid means to generate structural models for weakly bound protein–ligand complexes. Such weak complexes are often found at the beginning of programs of fragment based drug design and can be challenging to characterize using X-ray crystallography.

  14. Effect of some environmental ligands and fertilizers on humic acid complexation with strontium. Vol. 4

    Energy Technology Data Exchange (ETDEWEB)

    Helal, A A; Iman, D M; Khalifa, S M; Aly, H F [Hot Laborities Center, Atomic Energy Authority, Cairo, (Egypt)

    1996-03-01

    Strontium-90 represents one of the main radionuclides produced in fission products. Migration of strontium in the environment in case of accidental release is governed by many factors, besides its interaction with the materials present in the environment. Both humic acid and fertilizers are present on agricultural lands or aqueous streams. Other ligands such as EDTA, citrates, and phosphates are present in the environment. The binding and exchange of cations by the soil organic fractions is of importance in soil fertility because the supply of Na{sup +}, K{sup +}, Ca{sup 2+}, Mg{sup 2+} and certain micro nutrients (Cu{sup 2+}, Mn{sup 2+}, Zn{sup 2+} and Fe{sup 3+}) to plant is strongly dependent on the cation exchange capacity of the soil which may be induced by organic matters. The effect of the presence of certain fertilizers and some environmental ligands on the Sr-humate complex was studied. In general, the fertilizers and the complexing ligands investigated are compared with humic acid in its complexation with strontium. 6 figs.

  15. ProBiS-ligands: a web server for prediction of ligands by examination of protein binding sites.

    Science.gov (United States)

    Konc, Janez; Janežič, Dušanka

    2014-07-01

    The ProBiS-ligands web server predicts binding of ligands to a protein structure. Starting with a protein structure or binding site, ProBiS-ligands first identifies template proteins in the Protein Data Bank that share similar binding sites. Based on the superimpositions of the query protein and the similar binding sites found, the server then transposes the ligand structures from those sites to the query protein. Such ligand prediction supports many activities, e.g. drug repurposing. The ProBiS-ligands web server, an extension of the ProBiS web server, is open and free to all users at http://probis.cmm.ki.si/ligands. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. Spectrophotometric method for determination of bifunctional macrocyclic ligands in macrocyclic ligand-protein conjugates

    International Nuclear Information System (INIS)

    Dadachova, E.; Chappell, L.L.; Brechbiel, M.W.

    1999-01-01

    A simple spectrophotometric assay for determination of bifunctional polyazacarboxylate-macrocyclic ligands of different sizes that are conjugated to proteins has been developed for: 12-membered macrocycle DOTA (2-[4-nitrobenzyl]-1, 4, 7, 10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) and analogs, the 15-membered PEPA macrocycle (2-[4-nitrobenzyl]-1,4,7,10,13-pentaazacyclopentadecane-N,N',N'',N''',N'''' -pentaacetic acid), and the large 18-membered macrocycle HEHA (1,4,7,10,13,16-hexaazacyclooctadecane-N,N',N'',N''',N''''-hexaacetic acid). The method is based on titration of the blue-colored 1:1 Pb(II)-Arsenazo III (AAIII) complex with the polyazacarboxylate macrocyclic ligand in the concentration range of 0-2.5 μM, wherein color change occurring upon transchelation of the Pb(II) from the AAIII to the polyazamacrocyclic ligand is monitored at 656 nm. The assay is performed at ambient temperature within 20 min without any interfering interaction between the protein and Pb(II)-AA(III) complex. Thus, this method also provides a ligand-to-protein ratio (L/P ratio) that reflects the effective number of ligands per protein molecule available to radiolabeling. The method is not suitable for 14-membered TETA macrocycle (2-[4-nitrobenzyl]-1, 4, 8, 11-tetraazacyclotetradecane N,N',N'',N'''-tetraacetic acid) because of low stability constant of Pb(II)-TETA complex. The method is rapid, simple and may be customized for other polyazacarboxylate macrocyclic ligands

  17. A robust ligand exchange approach for preparing hydrophilic, biocompatible photoluminescent quantum dots

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Sujuan; Zhou, Changhua [Key Laboratory for Special Functional Materials of the Ministry of Education, Henan University, Kaifeng 475004 (China); Yuan, Hang [Life Science Division, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055 (China); Shen, Huaibin [Key Laboratory for Special Functional Materials of the Ministry of Education, Henan University, Kaifeng 475004 (China); Zhao, Wenxiu [Life Science Division, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055 (China); Ma, Lan, E-mail: malan@sz.tsinghua.edu.cn [Life Science Division, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055 (China); Li, Lin Song, E-mail: lsli@henu.edu.cn [Key Laboratory for Special Functional Materials of the Ministry of Education, Henan University, Kaifeng 475004 (China)

    2013-08-01

    Graphical abstract: - Highlights: • Aqueous CdSe/ZnS QDs were prepared using polymaleic anhydrides as capping ligand. • Effect of reaction temperature and time were systematically studied in the synthesis process. • Water-soluble QDs exhibited a good stability in physiological relevant environment. • The aqueous QDs were applied as biological probe to detect human embryonic stem cell. - Abstract: This paper describes a robust ligand exchange approach for preparing biocompatible CdSe/ZnS quantum dots (QDs) to make bioprobe for effective cell imaging. In this method, polymaleic anhydride (PMA) ligand are first used to replace original hydrophobic ligand (oleic acid) and form a protection shell with multiple hydrophilic groups to coat and protect CdSe/ZnS QDs. The as-prepared aqueous QDs exhibit small particle size, good colloidal stability in aqueous solutions with a wide range of pH, salt concentrations and under thermal treatment, which are necessary for biological applications. The use of this new class of aqueous QDs for effective cell imaging shows strong fluorescence signal to human embryonic stem cell, which demonstrate that PMA coated QDs are fully satisfied with the requirements of preparing high quality biological probe.

  18. Spray-coated ligand-free Cu2ZnSnS4 nanoparticle thin films

    DEFF Research Database (Denmark)

    Engberg, Sara Lena Josefin; Murthy, Swathi; Kofod, Guggi

    We have fabricated Cu2ZnSnS4 (CZTS) thin films from spray-coating ligand-free nanoparticle inks. The as-synthesized CZTS nanoparticles were inherently ligand-free [1], which allows the use of polar solvents, such as water and ethanol. Another advantage of these particles is that user- and environ......We have fabricated Cu2ZnSnS4 (CZTS) thin films from spray-coating ligand-free nanoparticle inks. The as-synthesized CZTS nanoparticles were inherently ligand-free [1], which allows the use of polar solvents, such as water and ethanol. Another advantage of these particles is that user......- and environmentally-friendly alkali metal chloride salts can be directly dissolved in controllable amounts. The homogeneous distribution of alkali metals in the ink allows uniform grain growth within the deposited absorber layer as a result of liquid phase assisted sintering. We find that particularly beneficial...... as an unquantifiable amount of ZnS. A Sono-tek spray-coating system is used which utilizes ultrasonic atomization. We investigate the effect of different binders, ink concentration, and spray-coating conditions, i.e. spray power, flow rate from syringe pump, distance between spray nozzle and the substrate, and time...

  19. Steric Maps to Evaluate the Role of Steric Hindrance on the IPr NHC Ligand

    KAUST Repository

    Poater, Albert

    2013-06-01

    Density functional theory (DFT) calculations were used to predict and rationalize the effect of the modification of the structure of the prototype 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) (IPr) N-heterocyclic carbene (NHC) ligand. The modification consists in the substitution of the methyl groups of ortho isopropyl substituent with phenyl groups, and here we plan to describe how such significant changes effect the metal environment and therefore the related catalytic behaviour by simple steric maps. Bearing in mind that there is a significant structural difference between IPr and IPr* ligands, that translated in different reactivity for several olefin metathesis reactions, here by means of DFT we characterize where the NHC ligand plays a more active role and where it is a simple spectator, or at least its modification does not significantly change its catalytic role/performance. Furthermore, this communication endeavours to modify further the skeleton of the IPr NHC ligand. The optimization of these bulky new systems go to the limits of the DFT computational method.

  20. Conformational study on cyclic melanocortin ligands and new insight into their binding mode at the MC4 receptor.

    Science.gov (United States)

    Grieco, Paolo; Brancaccio, Diego; Novellino, Ettore; Hruby, Victor J; Carotenuto, Alfonso

    2011-09-01

    The melanocortin receptors are involved in many physiological functions, including pigmentation, sexual function, feeding behavior, and energy homeostasis, making them potential targets to treat obesity, sexual dysfunction, etc. Understanding the basis of the ligand-receptor interactions is crucial for the design of potent and selective ligands for these receptors. The conformational preferences of the cyclic melanocortin ligands MTII (Ac-Nle(4)-c[Asp(5)-His(6)-DPhe(7)-Arg(8)-Trp(9)-Lys(10)]-NH(2)) and SHU9119 (Ac-Nle(4)-c[Asp(5)-His(6)-DNal(2')(7)-Arg(8)-Trp(9)-Lys(10)]-NH(2)), which show agonist and antagonist activity at the h-MC4R, respectively, were comprehensively investigated by solution NMR spectroscopy in different environments. In particular, water and water/DMSO (8:2) solutions were used as isotropic solutions and an aqueous solution of DPC (dodecylphosphocholine) micelles was used as a membrane mimetic environment. NMR-derived conformations of these two ligands were docked within h-MC4R models. NMR and docking studies revealed intriguing differences which can help explain the different activities of these two ligands. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  1. Ligand cluster-based protein network and ePlatton, a multi-target ligand finder.

    Science.gov (United States)

    Du, Yu; Shi, Tieliu

    2016-01-01

    Small molecules are information carriers that make cells aware of external changes and couple internal metabolic and signalling pathway systems with each other. In some specific physiological status, natural or artificial molecules are used to interact with selective biological targets to activate or inhibit their functions to achieve expected biological and physiological output. Millions of years of evolution have optimized biological processes and pathways and now the endocrine and immune system cannot work properly without some key small molecules. In the past thousands of years, the human race has managed to find many medicines against diseases by trail-and-error experience. In the recent decades, with the deepening understanding of life and the progress of molecular biology, researchers spare no effort to design molecules targeting one or two key enzymes and receptors related to corresponding diseases. But recent studies in pharmacogenomics have shown that polypharmacology may be necessary for the effects of drugs, which challenge the paradigm, 'one drug, one target, one disease'. Nowadays, cheminformatics and structural biology can help us reasonably take advantage of the polypharmacology to design next-generation promiscuous drugs and drug combination therapies. 234,591 protein-ligand interactions were extracted from ChEMBL. By the 2D structure similarity, 13,769 ligand emerged from 156,151 distinct ligands which were recognized by 1477 proteins. Ligand cluster- and sequence-based protein networks (LCBN, SBN) were constructed, compared and analysed. For assisting compound designing, exploring polypharmacology and finding possible drug combination, we integrated the pathway, disease, drug adverse reaction and the relationship of targets and ligand clusters into the web platform, ePlatton, which is available at http://www.megabionet.org/eplatton. Although there were some disagreements between the LCBN and SBN, communities in both networks were largely the same

  2. Towards ligand docking including explicit interface water molecules.

    Directory of Open Access Journals (Sweden)

    Gordon Lemmon

    Full Text Available Small molecule docking predicts the interaction of a small molecule ligand with a protein at atomic-detail accuracy including position and conformation the ligand but also conformational changes of the protein upon ligand binding. While successful in the majority of cases, docking algorithms including RosettaLigand fail in some cases to predict the correct protein/ligand complex structure. In this study we show that simultaneous docking of explicit interface water molecules greatly improves Rosetta's ability to distinguish correct from incorrect ligand poses. This result holds true for both protein-centric water docking wherein waters are located relative to the protein binding site and ligand-centric water docking wherein waters move with the ligand during docking. Protein-centric docking is used to model 99 HIV-1 protease/protease inhibitor structures. We find protease inhibitor placement improving at a ratio of 9:1 when one critical interface water molecule is included in the docking simulation. Ligand-centric docking is applied to 341 structures from the CSAR benchmark of diverse protein/ligand complexes [1]. Across this diverse dataset we see up to 56% recovery of failed docking studies, when waters are included in the docking simulation.

  3. Predicting Nanocrystal Shape through Consideration of Surface-Ligand Interactions

    KAUST Repository

    Bealing, Clive R.

    2012-03-27

    Density functional calculations for the binding energy of oleic acid-based ligands on Pb-rich {100} and {111} facets of PbSe nanocrystals determine the surface energies as a function of ligand coverage. Oleic acid is expected to bind to the nanocrystal surface in the form of lead oleate. The Wulff construction predicts the thermodynamic equilibrium shape of the PbSe nanocrystals. The equilibrium shape is a function of the ligand surface coverage, which can be controlled by changing the concentration of oleic acid during synthesis. The different binding energy of the ligand on the {100} and {111} facets results in different equilibrium ligand coverages on the facets, and a transition in the equilibrium shape from octahedral to cubic is predicted when increasing the ligand concentration during synthesis. © 2012 American Chemical Society.

  4. Prediction of GPCR-Ligand Binding Using Machine Learning Algorithms

    Directory of Open Access Journals (Sweden)

    Sangmin Seo

    2018-01-01

    Full Text Available We propose a novel method that predicts binding of G-protein coupled receptors (GPCRs and ligands. The proposed method uses hub and cycle structures of ligands and amino acid motif sequences of GPCRs, rather than the 3D structure of a receptor or similarity of receptors or ligands. The experimental results show that these new features can be effective in predicting GPCR-ligand binding (average area under the curve [AUC] of 0.944, because they are thought to include hidden properties of good ligand-receptor binding. Using the proposed method, we were able to identify novel ligand-GPCR bindings, some of which are supported by several studies.

  5. Mixed ligand chelates of rare earths in aqueous solution

    International Nuclear Information System (INIS)

    Lakhani, S.U.; Thakur, G.S.; Sangal, S.P.

    1981-01-01

    Mixed ligand chelates of the 1:1 trivalent lanthanoids-EDTA, HEDTA and NTA chelates-1, 2-Dihydroxybenzene (Pyrocatechol) have been investigated at 35degC and 0.2 M ionic strength maintained by NaC10 4 . The formation of mixed ligand chelates has been found in all cases. The formation of mixed ligand chelates with EDTA shows the coordination number of lanthanoids to be eight, while the mixed ligand chelates with HEDTA and NTA shows the coordination number to be seven and six respectively. The stability constants of mixed ligand chelates are smaller than the binary complexes. The order of stability constants with respect to primary ligands follows the order NTA>HEDTA>EDTA. With respect to metal ions the stability constants increases with the decrease in ionic radii such as Gd< Er< Yb. (author)

  6. New ' Bucky- ligands'. Potentially Monoanionic Terdentate Diamino Aryl Pincer Ligands Anchored to C60

    NARCIS (Netherlands)

    Koten, G. van; Meijer, M.D.; Gossage, R.A.; Jastrzebski, J.T.B.H.

    1998-01-01

    Two new methanofullerenes have been prepared by the reaction of C{6}{0} with diazo substituted, potentially monoanionic, terdentate diamino aryl ligands, yielding a mixture of the open valence [5, 6]- and closed valence [6,6]-isomers. Single isomers of the pure [6,6]-methanofullerenes were obtained

  7. LASSO-ligand activity by surface similarity order: a new tool for ligand based virtual screening.

    Science.gov (United States)

    Reid, Darryl; Sadjad, Bashir S; Zsoldos, Zsolt; Simon, Aniko

    2008-01-01

    Virtual Ligand Screening (VLS) has become an integral part of the drug discovery process for many pharmaceutical companies. Ligand similarity searches provide a very powerful method of screening large databases of ligands to identify possible hits. If these hits belong to new chemotypes the method is deemed even more successful. eHiTS LASSO uses a new interacting surface point types (ISPT) molecular descriptor that is generated from the 3D structure of the ligand, but unlike most 3D descriptors it is conformation independent. Combined with a neural network machine learning technique, LASSO screens molecular databases at an ultra fast speed of 1 million structures in under 1 min on a standard PC. The results obtained from eHiTS LASSO trained on relatively small training sets of just 2, 4 or 8 actives are presented using the diverse directory of useful decoys (DUD) dataset. It is shown that over a wide range of receptor families, eHiTS LASSO is consistently able to enrich screened databases and provides scaffold hopping ability.

  8. LASSO—ligand activity by surface similarity order: a new tool for ligand based virtual screening

    Science.gov (United States)

    Reid, Darryl; Sadjad, Bashir S.; Zsoldos, Zsolt; Simon, Aniko

    2008-06-01

    Virtual Ligand Screening (VLS) has become an integral part of the drug discovery process for many pharmaceutical companies. Ligand similarity searches provide a very powerful method of screening large databases of ligands to identify possible hits. If these hits belong to new chemotypes the method is deemed even more successful. eHiTS LASSO uses a new interacting surface point types (ISPT) molecular descriptor that is generated from the 3D structure of the ligand, but unlike most 3D descriptors it is conformation independent. Combined with a neural network machine learning technique, LASSO screens molecular databases at an ultra fast speed of 1 million structures in under 1 min on a standard PC. The results obtained from eHiTS LASSO trained on relatively small training sets of just 2, 4 or 8 actives are presented using the diverse directory of useful decoys (DUD) dataset. It is shown that over a wide range of receptor families, eHiTS LASSO is consistently able to enrich screened databases and provides scaffold hopping ability.

  9. New synthetic routes toward enantiopure nitrogen donor ligands

    OpenAIRE

    Sala, Xavier; Rodríguez, Anna M.; Rodríguez, Montserrat; Romero, Isabel; Parella, Teodor; Zelewsky, Alexander von; Llobet, Antoni; Benet-Buchholz, Jordi

    2008-01-01

    New polypyridylic chiral ligands, having either C₃ or lower symmetry, have been prepared via a de novo construction of the pyridine nucleus by means of Kröhnke methodology in the key step. The chiral moieties of these ligands originate from the monoterpen chiral pool, namely (-)-α-pinene ((-)-14, (-)-15) and (-)-myrtenal ((-)-9, (-)-10). Extension of the above-mentioned asymmetric synthesis procedure to the preparation of enantiopure derivatives of some commonly used polypyridylic ligands has...

  10. Selectivity in ligand recognition of G-quadruplex loops.

    Science.gov (United States)

    Campbell, Nancy H; Patel, Manisha; Tofa, Amina B; Ghosh, Ragina; Parkinson, Gary N; Neidle, Stephen

    2009-03-03

    A series of disubstituted acridine ligands have been cocrystallized with a bimolecular DNA G-quadruplex. The ligands have a range of cyclic amino end groups of varying size. The crystal structures show that the diagonal loop in this quadruplex results in a large cavity for these groups, in contrast to the steric constraints imposed by propeller loops in human telomeric quadruplexes. We conclude that the nature of the loop has a significant influence on ligand selectivity for particular quadruplex folds.

  11. Singular Value Decomposition and Ligand Binding Analysis

    Directory of Open Access Journals (Sweden)

    André Luiz Galo

    2013-01-01

    Full Text Available Singular values decomposition (SVD is one of the most important computations in linear algebra because of its vast application for data analysis. It is particularly useful for resolving problems involving least-squares minimization, the determination of matrix rank, and the solution of certain problems involving Euclidean norms. Such problems arise in the spectral analysis of ligand binding to macromolecule. Here, we present a spectral data analysis method using SVD (SVD analysis and nonlinear fitting to determine the binding characteristics of intercalating drugs to DNA. This methodology reduces noise and identifies distinct spectral species similar to traditional principal component analysis as well as fitting nonlinear binding parameters. We applied SVD analysis to investigate the interaction of actinomycin D and daunomycin with native DNA. This methodology does not require prior knowledge of ligand molar extinction coefficients (free and bound, which potentially limits binding analysis. Data are acquired simply by reconstructing the experimental data and by adjusting the product of deconvoluted matrices and the matrix of model coefficients determined by the Scatchard and McGee and von Hippel equation.

  12. Spectrochemical study on different ligand neodymium complexes

    International Nuclear Information System (INIS)

    Khomenko, V.S.; Lozinskij, M.O.; Fialkov, Yu.A.; Krasovskaya, L.I.; Rasshinina, T.A.; AN Ukrainskoj SSR, Kiev. Inst. Organicheskoj Khimii)

    1986-01-01

    A series of new adducts of neodymium complexes with 1, 1, 1, 5, 5, 5-hexafluoropentadione - 2, 4 and 2-heptafluoropropoxy-1, 1, 1, 2-tetrafluoro-5-phenylpentadione-3, 5: Nd(HFPTFPhPD) 3 x2H 2 O, Nd(HFPTFPhPD) 3 xDipy, Nd(HFPTFPhPD) 3 xPhen, Nd(HFPTFPhPD) 3 xDphen, Nd(HFA) 3 x2H 2 O, Nd(HFA) 3 xDipy, Nd(HFA) 3 xPhen, Nd(HFA) 3 xDphen, have been synthesized. Ways of their fragmentation under electron impact are established. Bond strength of additional ligands with central atom in the complexes studied is evaluated. Data on decomposition mechanisms of bicharged ions have been obtained for the first time. Addition of bis-heterocycles to neodymium three-ligand complexes changes the properties of the complexes - their thermal stability and photochemical stability increase, in certain cases their volatility increases

  13. Novel Somatostatin Receptor Ligands Therapies for Acromegaly

    Directory of Open Access Journals (Sweden)

    Rosa Maria Paragliola

    2018-03-01

    Full Text Available Surgery is considered the treatment of choice in acromegaly, but patients with persistent disease after surgery or in whom surgery cannot be considered require medical therapy. Somatostatin receptor ligands (SRLs octreotide (OCT, lanreotide, and the more recently approved pasireotide, characterized by a broader receptor ligand binding profile, are considered the mainstay in the medical management of acromegaly. However, in the attempt to offer a more efficacious and better tolerated medical approach, recent research has been aimed to override some limitations related to the use of currently approved drugs and novel SRLs therapies, with potential attractive features, have been proposed. These include both new formulation of older molecules and new molecules. Novel OCT formulations are aimed in particular to improve patients’ compliance and to reduce injection discomfort. They include an investigational ready-to-use subcutaneous depot OCT formulation (CAM2029, delivered via prefilled syringes and oral OCT that uses a “transient permeability enhancer” technology, which allows for OCT oral absorption. Another new delivery system is a long-lasting OCT implant (VP-003, which provide stable doses of OCT throughout a period of several months. Finally, a new SRL DG3173 (somatoprim seems to be more selective for GH secretion, suggesting possible advantages in the presence of hyperglycemia or diabetes. How much these innovations will actually be beneficial to acromegaly patients in real clinical practice remains to be seen.

  14. Estudo termogravimétrico do processo de sorção de metais pesados por resíduos sólidos orgânicos Thermogravimetric study of the sorption process of heavy metals in organic solid waste

    Directory of Open Access Journals (Sweden)

    Aldre Jorge Morais Barros

    2006-06-01

    Full Text Available A poluição de uma bacia hidrográfica pode causar alterações das propriedades físicas, químicas e biológicas da massa de água, comprometendo o seu uso para o consumo humano e para outros tipos de atividades, dependendo do grau de poluição ou contaminação. Os métodos de tratamentos convencionais de efluentes contendo metais pesados produzem quantidades significativas de subprodutos com características recalcitrantes, além de serem técnicas onerosas e de reprodutibilidade baixa. A busca por soluções mais baratas e definitivas levou ao desenvolvimento de tecnologias limpas, dentre estas tecnologias destaca-se o processo de sorção que baseia-se na utilização de substâncias absorventes desses elementos químicos. Este trabalho teve como objetivo avaliar o processo de sorção de metais pesados pelos resíduos sólidos orgânicos utilizando-se das técnicas de termogravimetria. Os resultados obtidos demonstraram que os perfis das curvas da termogravimetria dos resíduos sólidos orgânicos apresentam modificações significativas nas características físicas e químicas, quando submetidas ao processo de sorção dos metais pesados.Pollution of a hydrographic basin can cause alterations in physical, chemical and biological properties of water mass, committing its use for the human consumption and for other types of activities, depending on the contamination or pollution level. The conventional treatment methods for effluents containing heavy metals produce significant amounts of byproducts with recalcitrant characteristics; besides the techniques being onerous their reproducibility is low. The search for cheaper and definitive solutions led to the development of clean technologies, among these technologies the sorption process based on utilization of absorbent substances for these elements can be pointed out. This work has the objective of evaluating the sorption process of heavy metals by organic solid waste utilizing the

  15. Crystallization of bi-functional ligand protein complexes.

    Science.gov (United States)

    Antoni, Claudia; Vera, Laura; Devel, Laurent; Catalani, Maria Pia; Czarny, Bertrand; Cassar-Lajeunesse, Evelyn; Nuti, Elisa; Rossello, Armando; Dive, Vincent; Stura, Enrico Adriano

    2013-06-01

    Homodimerization is important in signal transduction and can play a crucial role in many other biological systems. To obtaining structural information for the design of molecules able to control the signalization pathways, the proteins involved will have to be crystallized in complex with ligands that induce dimerization. Bi-functional drugs have been generated by linking two ligands together chemically and the relative crystallizability of complexes with mono-functional and bi-functional ligands has been evaluated. There are problems associated with crystallization with such ligands, but overall, the advantages appear to be greater than the drawbacks. The study involves two matrix metalloproteinases, MMP-12 and MMP-9. Using flexible and rigid linkers we show that it is possible to control the crystal packing and that by changing the ligand-enzyme stoichiometric ratio, one can toggle between having one bi-functional ligand binding to two enzymes and having the same ligand bound to each enzyme. The nature of linker and its point of attachment on the ligand can be varied to aid crystallization, and such variations can also provide valuable structural information about the interactions made by the linker with the protein. We report here the crystallization and structure determination of seven ligand-dimerized complexes. These results suggest that the use of bi-functional drugs can be extended beyond the realm of protein dimerization to include all drug design projects. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Superior serum half life of albumin tagged TNF ligands

    International Nuclear Information System (INIS)

    Mueller, Nicole; Schneider, Britta; Pfizenmaier, Klaus; Wajant, Harald

    2010-01-01

    Due to their immune stimulating and apoptosis inducing properties, ligands of the TNF family attract increasing interest as therapeutic proteins. A general limitation of in vivo applications of recombinant soluble TNF ligands is their notoriously rapid clearance from circulation. To improve the serum half life of the TNF family members TNF, TWEAK and TRAIL, we genetically fused soluble variants of these molecules to human serum albumin (HSA). The serum albumin-TNF ligand fusion proteins were found to be of similar bioactivity as the corresponding HSA-less counterparts. Upon intravenous injection (i.v.), serum half life of HSA-TNF ligand fusion proteins, as determined by ELISA, was around 15 h as compared to approximately 1 h for all of the recombinant control TNF ligands without HSA domain. Moreover, serum samples collected 6 or 24 h after i.v. injection still contained high TNF ligand bioactivity, demonstrating that there is only limited degradation/inactivation of circulating HSA-TNF ligand fusion proteins in vivo. In a xenotransplantation model, significantly less of the HSA-TRAIL fusion protein compared to the respective control TRAIL protein was required to achieve inhibition of tumor growth indicating that the increased half life of HSA-TNF ligand fusion proteins translates into better therapeutic action in vivo. In conclusion, our data suggest that genetic fusion to serum albumin is a powerful and generally applicable mean to improve bioavailability and in vivo activity of TNF ligands.

  17. Spectra of fluorinated rare earth. beta. -diketonates with added ligands

    Energy Technology Data Exchange (ETDEWEB)

    Khomenko, V.S.; Lozinskij, M.O.; Fialkov, Yu.A.; Rasshinina, T.A.; Krasovskaya, L.I. (AN Belorusskoj SSR, Minsk. Inst. Fiziki; AN Ukrainskoj SSR, Kiev. Inst. Organicheskoj Khimii)

    1984-01-01

    Different-ligand rare earth complexes are synthesized. Fluorated ..beta..-diketones, triethylphosphine oxide and trifluoracetic acid are used as active ligands. Mass-spectra of low and high resolution are taken at the energy of ionizing electrons of 70 eV, as well as luminescence spectra of complexes. Fragmentation ways of complexes decomposition under electron shock are studied. A series of changing the bound strength of additional ligands with europium in mixed complexes is determined. It is shown that the introduction of additional ligands can purposefully change physical and chemical properties of complexes.

  18. Implicit ligand theory for relative binding free energies

    Science.gov (United States)

    Nguyen, Trung Hai; Minh, David D. L.

    2018-03-01

    Implicit ligand theory enables noncovalent binding free energies to be calculated based on an exponential average of the binding potential of mean force (BPMF)—the binding free energy between a flexible ligand and rigid receptor—over a precomputed ensemble of receptor configurations. In the original formalism, receptor configurations were drawn from or reweighted to the apo ensemble. Here we show that BPMFs averaged over a holo ensemble yield binding free energies relative to the reference ligand that specifies the ensemble. When using receptor snapshots from an alchemical simulation with a single ligand, the new statistical estimator outperforms the original.

  19. Computational fragment-based screening using RosettaLigand: the SAMPL3 challenge

    Science.gov (United States)

    Kumar, Ashutosh; Zhang, Kam Y. J.

    2012-05-01

    SAMPL3 fragment based virtual screening challenge provides a valuable opportunity for researchers to test their programs, methods and screening protocols in a blind testing environment. We participated in SAMPL3 challenge and evaluated our virtual fragment screening protocol, which involves RosettaLigand as the core component by screening a 500 fragments Maybridge library against bovine pancreatic trypsin. Our study reaffirmed that the real test for any virtual screening approach would be in a blind testing environment. The analyses presented in this paper also showed that virtual screening performance can be improved, if a set of known active compounds is available and parameters and methods that yield better enrichment are selected. Our study also highlighted that to achieve accurate orientation and conformation of ligands within a binding site, selecting an appropriate method to calculate partial charges is important. Another finding is that using multiple receptor ensembles in docking does not always yield better enrichment than individual receptors. On the basis of our results and retrospective analyses from SAMPL3 fragment screening challenge we anticipate that chances of success in a fragment screening process could be increased significantly with careful selection of receptor structures, protein flexibility, sufficient conformational sampling within binding pocket and accurate assignment of ligand and protein partial charges.

  20. HPPD: ligand- and target-based virtual screening on a herbicide target.

    Science.gov (United States)

    López-Ramos, Miriam; Perruccio, Francesca

    2010-05-24

    Hydroxyphenylpyruvate dioxygenase (HPPD) has proven to be a very successful target for the development of herbicides with bleaching properties, and today HPPD inhibitors are well established in the agrochemical market. Syngenta has a long history of HPPD-inhibitor research, and HPPD was chosen as a case study for the validation of diverse ligand- and target-based virtual screening approaches to identify compounds with inhibitory properties. Two-dimensional extended connectivity fingerprints, three-dimensional shape-based tools (ROCS, EON, and Phase-shape) and a pharmacophore approach (Phase) were used as ligand-based methods; Glide and Gold were used as target-based. Both the virtual screening utility and the scaffold-hopping ability of the screening tools were assessed. Particular emphasis was put on the specific pitfalls to take into account for the design of a virtual screening campaign in an agrochemical context, as compared to a pharmaceutical environment.

  1. Calculating the mean time to capture for tethered ligands and its effect on the chemical equilibrium of bound ligand pairs.

    Science.gov (United States)

    Shen, Lu; Decker, Caitlin G; Maynard, Heather D; Levine, Alex J

    2016-09-01

    We present here the calculation of the mean time to capture of a tethered ligand to the receptor. This calculation is then used to determine the shift in the partitioning between (1) free, (2) singly bound, and (3) doubly bound ligands in chemical equilibrium as a function of the length of the tether. These calculations are used in the research article Fibroblast Growth Factor 2 Dimer with Superagonist in vitro Activity Improves Granulation Tissue Formation During Wound Healing (Decker et al., in press [1]) to explain quantitatively how changes in polymeric linker length in the ligand dimers modifies the efficacy of these molecules relative to that of free ligands.

  2. Reversibly Switchable, pH-Dependent Peptide Ligand Binding via 3,5-Diiodotyrosine Substitutions.

    Science.gov (United States)

    Ngambenjawong, Chayanon; Sylvestre, Meilyn; Gustafson, Heather H; Pineda, Julio Marco B; Pun, Suzie H

    2018-04-20

    Cell type-specific targeting ligands utilized in drug delivery applications typically recognize receptors that are overexpressed on the cells of interest. Nonetheless, these receptors may also be expressed, to varying extents, on off-target cells, contributing to unintended side effects. For the selectivity profile of targeting ligands in cancer therapy to be improved, stimuli-responsive masking of these ligands with acid-, redox-, or enzyme-cleavable molecules has been reported, whereby the targeting ligands are exposed in specific environments, e.g., acidic tumor hypoxia. One possible drawback of these systems lies in their one-time, permanent trigger, which enables the "demasked" ligands to bind off-target cells if released back into the systemic circulation. A promising strategy to address the aforementioned problem is to design ligands that show selective binding based on ionization state, which may be microenvironment-dependent. In this study, we report a systematic strategy to engineer low pH-selective targeting peptides using an M2 macrophage-targeting peptide (M2pep) as an example. 3,5-Diiodotyrosine mutagenesis into native tyrosine residues of M2pep confers pH-dependent binding behavior specific to acidic environment (pH 6) when the amino acid is protonated into the native tyrosine-like state. At physiological pH of 7.4, the hydroxyl group of 3,5-diiodotyrosine on the peptide is deprotonated leading to interruption of the peptide native binding property. Our engineered pH-responsive M2pep (Ac-Y-Î-Î) binds target M2 macrophages more selectively at pH 6 than at pH 7.4. In addition, 3,5-diiodotyrosine substitutions also improve serum stability of the peptide. Finally, we demonstrate pH-dependent reversibility in target binding via a postbinding peptide elution study. The strategy presented here should be applicable for engineering pH-dependent functionality of other targeting peptides with potential applications in physiology-dependent in vivo targeting

  3. Role of ligands in permanganate oxidation of organics.

    Science.gov (United States)

    Jiang, Jin; Pang, Su-Yan; Ma, Jun

    2010-06-01

    We previously demonstrated that several ligands such as phosphate, pyrophosphate, EDTA, and humic acid could significantly enhance permanganate oxidation of triclosan (one phenolic biocide), which was explained by the contribution of ligand-stabilized reactive manganese intermediates in situ formed upon permanganate reduction. To further understand the underlying mechanism, we comparatively investigated the influence of ligands on permanganate oxidation of bisphenol A (BPA, one phenolic endocrine-disrupting chemical), carbamazepine (CBZ, a pharmaceutical containing the olefinic group), and methyl p-tolyl sulfoxide (TMSO, a typical oxygen-atom acceptor). Selected ligands exerted oxidation enhancement for BPA but had negligible influence for CBZ and TMSO. This was mainly attributed to the effects of identified Mn(III) complexes, which would otherwise disproportionate spontaneously in the absence of ligands. The one-electron oxidant Mn(III) species exhibited no reactivity toward CBZ and TMSO for which the two-electron oxygen donation may be the primary oxidation mechanism but readily oxidized BPA. The latter case was a function of pH, the complexing ligand, and the molar [Mn(III)]:[ligand] ratio, generally consistent with the patterns of ligand-affected permanganate oxidation. Moreover, the combination of the one-electron reduction of Mn(III) (Mn(III) + e(-) -->Mn(II)) and the Mn(VII)/Mn(II) reaction in excess ligands (Mn(VII) + 4Mn(II) ----> (ligands) 5Mn(III)) suggested a catalytic role of the Mn(III)/Mn(II) pair in permanganate oxidation of some phenolics in the presence of ligands.

  4. Precipitation and growth of zinc sulfide nanoparticles in the presence of thiol-containing natural organic ligands.

    Science.gov (United States)

    Lau, Boris L T; Hsu-Kim, Heileen

    2008-10-01

    In sulfidic aquatic systems, metal sulfides can control the mobility and bioavailability of trace metal pollutants such as zinc, mercury, and silver. Nanoparticles of ZnS and other metal sulfides are known to exist in oxic and anoxic waters. However, the processes that lead to their persistence in the aquatic environment are relatively unknown. The objective of this study was to evaluate the importance of dissolved natural organics in stabilizing nanoparticulate ZnS that precipitates under environmentally relevant conditions. Precipitation and growth of ZnS particles were investigated in the presence of dissolved humic acid and low-molecular weight organic acids that are prevalent in sediment porewater. Dynamic light scattering was used to monitor the hydrodynamic diameter of particles precipitating in laboratory solutions. Zn speciation was also measured by filtering the ZnS solutions (precipitation experiments and not to the dissolved organic ligands. X-ray photoelectron spectroscopy and electron microscopy were used to confirm that amorphous particles containing Zn and S were precipitating in the suspensions. Observed growth rates of ZnS particles varied by orders of magnitude, depending on the type and concentration of organic ligand in solution. In the presence of humic acid and thiol-containing ligands (cysteine, glutathione, and thioglycolate), observed growth rates decreased by 1-3 orders of magnitude relative to controls without the ligands. In contrast, growth rates of the particles were consistently within 1 order of magnitude of the ligand-free control when oxygen- and amine-containing ligands (oxalate, serine, and glycolate) were present Furthermore, particle growth rates decreased with an increase in thiol concentration and increased with NaNO3 electrolyte concentration. These studies suggest that specific surface interactions with thiol-containing organics may be one factor that contributes to the persistence of naturally occurring and anthropogenic

  5. Remoção de níquel(II de soluções aquosas pela biomassa Sargassum filipendula em múltiplos ciclos de sorção-dessorção - DOI: 10.4025/actascitechnol.v31i1.840

    Directory of Open Access Journals (Sweden)

    Araceli Aparecida Seolatto

    2009-04-01

    Full Text Available Foi estudado o desempenho da alga marinha Sargassum filipendula na remoção de níquel de uma solução de concentração de 50 mg L-1 em pH 3,5, em colunas de leito fixo que operam em ciclos de adsorção/dessorção. Foram testados dois sistemas de eluição; o primeiro operou com a passagem direta e o segundo com a recirculação do eluente. Em seguida, foram realizados dez ciclos consecutivos de sorção-dessorção em duas colunas de leito fixo, uma regenerada com o eluente H2SO4 (0,1 M e outra com MgSO4/H2SO4 (pH 3, em sistema de recirculação do eluente. As etapas de sorção e dessorção foram realizadas em 30 e 2h, respectivamente, representando 20 dias de uso contínuo da biomassa. Foi observada alta quantidade recuperada de níquel nas etapas de eluição (aproximadamente 95%. Ao final do décimo ciclo, verificou-se que a alga Sargassum filipendula continuava apresentando valores elevados da capacidade de remoção de níquel da solução, mostrando-se como alternativa eficiente de tratamento de águas residuárias contendo metais. A regeneração da biomassa apresentou baixo custo, além de ter facilitado o processo de tratamento que dispensou trocas sucessivas da biomassa.

  6. Radiation sensitization by an iodine-labelled DNA ligand

    Energy Technology Data Exchange (ETDEWEB)

    Martin, R F; Murray, V; D' Cunha, G; Pardee, M; Haigh, A; Hodgson, G S [Peter MacCallum Cancer Inst., Melbourne (Australia); Kampouris, E; Kelly, D P [Melbourne Univ., Parkville (Australia)

    1990-05-01

    An iodinated DNA ligand, iodoHoechst 33258, which binds in the minor groove of DNA, enhances DNA strand breakage and cell killing by UV-A irradiation. The sites of UV-induced strand breaks reflect the known sequence specificity of the ligand. (author).

  7. Identifying Marine Copper-Binding Ligands in Seawater

    Science.gov (United States)

    Whitby, H.; Hollibaugh, J. T.; Maldonado, M. T.; Ouchi, S.; van den Berg, S. M.

    2016-02-01

    Complexation reactions are important because they affect the bioavailability of trace metals such as copper and iron. For example, organic complexation can determine whether copper is a limiting or a toxic micronutrient at natural levels. Copper competes with iron for complexing ligands, and when iron is limiting, copper can also substitute for iron in some metabolic pathways. The speciation of copper can be measured using complexing capacity titrations, which provide the concentration of individual ligand classes (L1, L2 etc.) and the complex stabilities (log K). Using methods recently developed in our laboratory, we show that the ligands within these classes can be measured independently of titrations, thus confirming the titration method and simultaneously identifying the ligands within each class. Thiols were identified as the L1 ligand class and humic compounds as the weaker L2 class in samples from coastal Georgia, USA, collected monthly from April to December. Log K values of the ligand complexes were consistent with values expected for thiols and humic substances. Recent results from culture studies and from samples collected along Line P, a coastal - oceanic transect in the HNLC region of the NE subarctic Pacific, will be presented in comparison to the estuarine results. This comparison will help to broaden our perspective on copper complexation and the ligands responsible, furthering our understanding of ligand sources and life cycles.

  8. Some new IIB group complexes of an imidazolidine ligand ...

    Indian Academy of Sciences (India)

    The spectral data indicate that the ligand is coordinated to zinc(II) as a bidentate ligand in imidazolidine form but it binds to ..... confirmed by determination of the minimum inhibitory ...... Yue F, Gang L, Xiu-Mei T, Ji-De W and Wei W 2008. Chin.

  9. Mixed-Ligand Complexes Of Nickel (II) With 2-Acetylpyridine ...

    African Journals Online (AJOL)

    The preparation and spectral properties of five nickel (II) mixed-ligands complexes (Ni [2-Actsc.Y]CI2), derived from 2-acetylpyridinethiosermicarbazones and some nitrogen/sulphur monodentate ligands such as thiophene, ammonia, picoline, pyridine and aniline are described. The complexes have been characterized on ...

  10. Synthesis of meta-substituted monodentate phosphinite ligands and ...

    Indian Academy of Sciences (India)

    SATEJ S DESHMUKH

    from organic synthesis, phosphinite ligands find appli- cations in a variety of ... thesis of meta-substituted phosphinite ligands is rarely reported.18 This is most ... 1.9 μm; mobile phase used, 90% methanol + 10% water +. 0.1% formic acid) ...

  11. The Evaluation of Novel Camphor-derived Pyridyl Ligands as ...

    African Journals Online (AJOL)

    NJD

    2009-03-03

    Mar 3, 2009 ... The structures of the copper (II) complexes of the ligands were calculated using ONIOM density functional theory and the results suggest that chiral induction to the alkene functional group is indeed lacking. This explains the moderate experimental selectivities obtained. KEYWORDS. Camphor ligands ...

  12. The Evaluation of Novel Camphor-derived Pyridyl Ligands as ...

    African Journals Online (AJOL)

    The structures of the copper (II) complexes of the ligands were calculated using ONIOM density functional theory and the results suggest that chiral induction to the alkene functional group is indeed lacking. This explains the moderate experimental selectivities obtained. Keywords: Camphor ligands, asymmetric catalysis, ...

  13. THERMODYNAMICS OF PROTEIN-LIGAND INTERACTIONS AND THEIR ANALYSIS

    Directory of Open Access Journals (Sweden)

    Rummi Devi Saini

    2017-11-01

    Full Text Available Physiological processes are controlled mainly by intermolecular recognition mechanisms which involve protein–protein and protein–ligand interactions with a high specificity and affinity to form a specific complex. Proteins being an important class of macromolecules in biological systems, it is important to understand their actions through binding to other molecules of proteins or ligands. In fact, the binding of low molecular weight ligands to proteins plays a significant role in regulating biological processes such as cellular metabolism and signal transmission. Therefore knowledge of the protein–ligand interactions and the knowledge of the mechanisms involved in the protein-ligand recognition and binding are key in understanding biology at molecular level which will facilitate the discovery, design, and development of drugs. In this review, the mechanisms involved in protein–ligand binding, the binding kinetics, thermodynamic concepts and binding driving forces are discussed. Thermodynamic mechanisms involved in a few important protein-ligand binding are described. Various spectroscopic, non-spectroscopic and computational method for analysis of protein–ligand binding are also discussed.

  14. Polymerization catalysts containing electron-withdrawing amide ligands

    Science.gov (United States)

    Watkin, John G.; Click, Damon R.

    2002-01-01

    The present invention describes methods of making a series of amine-containing organic compounds which are used as ligands for group 3-10 and lanthanide metal compounds. The ligands have electron-withdrawing groups bonded to them. The metal compounds, when combined with a cocatalyst, are catalysts for the polymerization of olefins.

  15. Mixed ligand chelate therapy for plutonium and cadmium poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Schubert, J; Derr, S K [Hope Coll., Holland, MI (USA)

    1978-09-28

    Some experiments with mice are described in which complete removal of tissue deposits of /sup 239/Pu and prevention of mortality in animals given lethal doses of Cd were achieved using a mixed ligand chelate treatment (MLC). The mixed ligand consisted of diethylenetriaminepentaacetic acid and salicylic acid.

  16. Immobilisation of ligands by radio-derivatized polymers

    International Nuclear Information System (INIS)

    Varga, J.M.; Fritsch, P.

    1995-01-01

    The invention relates to radio-derivatized polymers and a method of producing them by contacting non-polymerizable conjugands with radiolysable polymers in the presence of irradiation. The resulting radio-derivatized polymers can be further linked with ligand of organic or inorganic nature to immobilize such ligands. 2 figs., 5 tabs

  17. Correcting binding parameters for interacting ligand-lattice systems

    Science.gov (United States)

    Hervy, Jordan; Bicout, Dominique J.

    2017-07-01

    Binding of ligands to macromolecules is central to many functional and regulatory biological processes. Key parameters characterizing ligand-macromolecule interactions are the stoichiometry, inducing the number of ligands per macromolecule binding site, and the dissociation constant, quantifying the ligand-binding site affinity. Both these parameters can be obtained from analyses of classical saturation experiments using the standard binding equation that offers the great advantage of mathematical simplicity but becomes an approximation for situations of interest when a ligand binds and covers more than one single binding site on the macromolecule. Using the framework of car-parking problem with latticelike macromolecules where each ligand can cover simultaneously several consecutive binding sites, we showed that employing the standard analysis leads to underestimation of binding parameters, i.e., ligands appear larger than they actually are and their affinity is also greater than it is. Therefore, we have derived expressions allowing to determine the ligand size and true binding parameters (stoichiometry and dissociation constant) as a function of apparent binding parameters retrieved from standard saturation experiments.

  18. Predicting Nanocrystal Shape through Consideration of Surface-Ligand Interactions

    KAUST Repository

    Bealing, Clive R.; Baumgardner, William J.; Choi, Joshua J.; Hanrath, Tobias; Hennig, Richard G.

    2012-01-01

    Density functional calculations for the binding energy of oleic acid-based ligands on Pb-rich {100} and {111} facets of PbSe nanocrystals determine the surface energies as a function of ligand coverage. Oleic acid is expected to bind

  19. Lanthanide(III) complexes with tridentate Schiff base ligand ...

    African Journals Online (AJOL)

    The X-ray study reveals isotopic Nd/Sm binuclear structures were each metal ion is nine-coordinated in the same fashion. Both metal centers have distorted tricapped trigonal prism geometry, with the Schiff base acting as tridentate ligand. The DPPH· radical scavenging effects of the Schiff base ligand and its Ln(III) ...

  20. Models of protein-ligand crystal structures: trust, but verify.

    Science.gov (United States)

    Deller, Marc C; Rupp, Bernhard

    2015-09-01

    X-ray crystallography provides the most accurate models of protein-ligand structures. These models serve as the foundation of many computational methods including structure prediction, molecular modelling, and structure-based drug design. The success of these computational methods ultimately depends on the quality of the underlying protein-ligand models. X-ray crystallography offers the unparalleled advantage of a clear mathematical formalism relating the experimental data to the protein-ligand model. In the case of X-ray crystallography, the primary experimental evidence is the electron density of the molecules forming the crystal. The first step in the generation of an accurate and precise crystallographic model is the interpretation of the electron density of the crystal, typically carried out by construction of an atomic model. The atomic model must then be validated for fit to the experimental electron density and also for agreement with prior expectations of stereochemistry. Stringent validation of protein-ligand models has become possible as a result of the mandatory deposition of primary diffraction data, and many computational tools are now available to aid in the validation process. Validation of protein-ligand complexes has revealed some instances of overenthusiastic interpretation of ligand density. Fundamental concepts and metrics of protein-ligand quality validation are discussed and we highlight software tools to assist in this process. It is essential that end users select high quality protein-ligand models for their computational and biological studies, and we provide an overview of how this can be achieved.

  1. Ligand Binding Domain Protein in Tetracycline-Inducible Expression

    African Journals Online (AJOL)

    Purpose: To investigate tetracycline-inducible expression system for producing clinically usable, highquality liver X receptor ligand-binding domain recombinant protein. Methods: In this study, we have expressed and purified the recombinant liver X receptor β-ligand binding domain proteins in E. coli using a tetracycline ...

  2. Interactions of rare earth elements with bacteria and organic ligands

    International Nuclear Information System (INIS)

    Ozaki, Takuo; Suzuki, Yoshinori; Nankawa, Takuya; Yoshida, Takahiro; Ohnuki, Toshihiko; Kimura, Takaumi; Francis, Arokiasamy J.

    2006-01-01

    We investigated the interactions of rare earth elements (REEs) Eu(III) and/or Ce(III, IV) with the common soil bacterium Pseudomonas fluorescens and organic ligands, such as malic acid, citric acid, a siderophore (DFO), cellulose, chitin, and chitosan. Malic acid formed complexes with Eu(III), but degradation of malic acid was observed when the ratio of malic acid to Eu(III) was higher than 100. Citric acid formed a stoichiometric complex with Eu(III) that was not degraded by P. fluorescens. Adsorption of Eu(III) from the DFO complex occurred as a free ion dissociated from DFO and not as the Eu(III)-DFO complex. Cerium(III) was oxidized to Ce(IV) during complexation with DFO to form the Ce(IV)-DFO complex. Time-resolved laser-induced fluorescence spectroscopy (TRLFS) analysis showed that cellulose, chitin, and chitosan, respectively, formed a weak complex, an inner-spherical complex, and an outer-spherical complex with Eu(III). This method also demonstrated that the coordination environment of Eu(III) adsorbed on P. fluorescens possessed similar characteristics to that of chitin, and revealed that adsorption of Eu(III) on P. fluorescens was through a multidentate and predominantly inner-spherical coordination

  3. Novel peptide ligand with high binding capacity for antibody purification

    DEFF Research Database (Denmark)

    Lund, L. N.; Gustavsson, P. E.; Michael, R.

    2012-01-01

    Small synthetic ligands for protein purification have become increasingly interesting with the growing need for cheap chromatographic materials for protein purification and especially for the purification of monoclonal antibodies (mAbs). Today, Protein A-based chromatographic resins are the most...... commonly used capture step in mAb down stream processing; however, the use of Protein A chromatography is less attractive due to toxic ligand leakage as well as high cost. Whether used as an alternative to the Protein A chromatographic media or as a subsequent polishing step, small synthetic peptide...... ligands have an advantage over biological ligands; they are cheaper to produce, ligand leakage by enzymatic degradation is either eliminated or significantly reduced, and they can in general better withstand cleaning in place (CIP) conditions such as 0.1 M NaOH. Here, we present a novel synthetic peptide...

  4. Identification and characterization of PPARα ligands in the hippocampus.

    Science.gov (United States)

    Roy, Avik; Kundu, Madhuchhanda; Jana, Malabendu; Mishra, Rama K; Yung, Yeni; Luan, Chi-Hao; Gonzalez, Frank J; Pahan, Kalipada

    2016-12-01

    Peroxisome proliferator-activated receptor-α (PPARα) regulates hepatic fatty acid catabolism and mediates the metabolic response to starvation. Recently we found that PPARα is constitutively activated in nuclei of hippocampal neurons and controls plasticity via direct transcriptional activation of CREB. Here we report the discovery of three endogenous PPARα ligands-3-hydroxy-(2,2)-dimethyl butyrate, hexadecanamide, and 9-octadecenamide-in mouse brain hippocampus. Mass spectrometric detection of these compounds in mouse hippocampal nuclear extracts, in silico interaction studies, time-resolved FRET analyses, and thermal shift assay results clearly indicated that these three compounds served as ligands of PPARα. Site-directed mutagenesis studies further revealed that PPARα Y464 and Y314 are involved in binding these hippocampal ligands. Moreover, these ligands activated PPARα and upregulated the synaptic function of hippocampal neurons. These results highlight the discovery of hippocampal ligands of PPARα capable of modulating synaptic functions.

  5. Ligand Electron Density Shape Recognition Using 3D Zernike Descriptors

    Science.gov (United States)

    Gunasekaran, Prasad; Grandison, Scott; Cowtan, Kevin; Mak, Lora; Lawson, David M.; Morris, Richard J.

    We present a novel approach to crystallographic ligand density interpretation based on Zernike shape descriptors. Electron density for a bound ligand is expanded in an orthogonal polynomial series (3D Zernike polynomials) and the coefficients from this expansion are employed to construct rotation-invariant descriptors. These descriptors can be compared highly efficiently against large databases of descriptors computed from other molecules. In this manuscript we describe this process and show initial results from an electron density interpretation study on a dataset containing over a hundred OMIT maps. We could identify the correct ligand as the first hit in about 30 % of the cases, within the top five in a further 30 % of the cases, and giving rise to an 80 % probability of getting the correct ligand within the top ten matches. In all but a few examples, the top hit was highly similar to the correct ligand in both shape and chemistry. Further extensions and intrinsic limitations of the method are discussed.

  6. Automated identification of crystallographic ligands using sparse-density representations

    International Nuclear Information System (INIS)

    Carolan, C. G.; Lamzin, V. S.

    2014-01-01

    A novel procedure for identifying ligands in macromolecular crystallographic electron-density maps is introduced. Density clusters in such maps can be rapidly attributed to one of 82 different ligands in an automated manner. A novel procedure for the automatic identification of ligands in macromolecular crystallographic electron-density maps is introduced. It is based on the sparse parameterization of density clusters and the matching of the pseudo-atomic grids thus created to conformationally variant ligands using mathematical descriptors of molecular shape, size and topology. In large-scale tests on experimental data derived from the Protein Data Bank, the procedure could quickly identify the deposited ligand within the top-ranked compounds from a database of candidates. This indicates the suitability of the method for the identification of binding entities in fragment-based drug screening and in model completion in macromolecular structure determination

  7. The affinity of the uranyl ion for nitrogen donor ligands

    International Nuclear Information System (INIS)

    Jarvis, N.V.; De Sousa, A.S.; Hancock, R.D.

    1992-01-01

    Established ligand design principles are used to predict the solution chemistry of UO 2 2+ with nitrogen donor ligands which do not contain carboxylate donors. pK a 's of the nitrogen donors are lowered by addition of hydroxylalkyl groups causing UO 2 2+ to have a greater affinity for these ligands than for hydroxide. Potentiometric studies using the ligands N,N,N',N',N''-pentakis(2-hydroxypropyl)-1,4,7-triazaheptane; N,N,N',N',N''-pentakis(2-hydroxyethyl)-1,4,7-triazaheptane; N,N,N',N'-tetrakis(2-hydroxypropyl)1,2-diaminoethane, N,N,N',N'-tetrakis(2-hydroxyethyl)-trans-1,2-diaminocyclohexane; 1,4,8,11-tetrakis(2-hydroxyethyl)-1,4,8,11-tetraazacyclotetradecane and N,N-bis(2-hydroxyethyl)glycine with UO 2 2+ showed that UO 2 2+ has a considerable aqueous solution chemistry with these ligands. (orig.)

  8. Regulation mechanisms of the FLT3-ligand after irradiation

    International Nuclear Information System (INIS)

    Prat-Lepesant, M.

    2005-06-01

    The hematopoietic compartment is one of the most severely damaged after chemotherapy, radiotherapy or accidental irradiations. Whatever its origin, the resulting damage to the bone marrow remains difficult to evaluate. Thus, it would be of great interest to get a biological indicator of residual hematopoiesis in order to adapt the treatment to each clinical situation. Recent results indicated that the plasma Flt3 ligand concentration was increased in patients suffering from either acquired or induced aplasia, suggesting that Flt3 ligand might be useful as a biological indicator of bone marrow status. We thus followed in a mouse model as well as in several clinical situations the variations in plasma Flt3 ligand concentration, after either homogeneous or heterogeneous irradiations. These variations were correlated to the number of hematopoietic progenitors and to other parameters such as duration and depth of pancytopenia. The results indicated that the concentration of Flt3 ligand in the blood reflects the bone marrow status, and that the follow-up of plasma Flt3 ligand concentration could give predictive information about the bone marrow function and the duration and severity of pancytopenia and thrombocytopenia. Nevertheless, the clinical use of Flt3 ligand as a biological indicator of bone marrow damage require the knowledge of the mechanisms regulating the variations in plasma Flt3 ligand concentration. We thus developed a study in the mouse model. The results indicated that the variations in plasma Flt3 ligand variations were not solely due to a balance between its production by lymphoid cells and its consumption by hematopoietic cells. Moreover, we showed that T lymphocytes are not the main regulator of plasma Flt3 ligand concentration as previously suggested, and that other cell types, possibly including bone marrow stromal cells, might be strongly implicated. These results also suggest that the Flt3 ligand is a main systemic regulator of hematopoiesis

  9. Cellular trafficking of quantum dot-ligand bioconjugates and their induction of changes in normal routing of unconjugated ligands

    DEFF Research Database (Denmark)

    Tekle, Christina; van Deurs, Bo; Sandvig, Kirsten

    2008-01-01

    Can quantum dots (Qdots) act as relevant intracellular probes to investigate routing of ligands in live cells? The intracellular trafficking of Qdots that were coupled to the plant toxin ricin, Shiga toxin, or the ligand transferrin (Tf) was studied by confocal fluorescence microscopy. The Tf...

  10. Gas adsorption and gas mixture separations using mixed-ligand MOF material

    Science.gov (United States)

    Hupp, Joseph T [Northfield, IL; Mulfort, Karen L [Chicago, IL; Snurr, Randall Q [Evanston, IL; Bae, Youn-Sang [Evanston, IL

    2011-01-04

    A method of separating a mixture of carbon dioxiode and hydrocarbon gas using a mixed-ligand, metal-organic framework (MOF) material having metal ions coordinated to carboxylate ligands and pyridyl ligands.

  11. Regulation mechanisms of the FLT3-ligand after irradiation; Mecanismes de regulation du FLT3-ligand apres irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Prat-Lepesant, M

    2005-06-15

    The hematopoietic compartment is one of the most severely damaged after chemotherapy, radiotherapy or accidental irradiations. Whatever its origin, the resulting damage to the bone marrow remains difficult to evaluate. Thus, it would be of great interest to get a biological indicator of residual hematopoiesis in order to adapt the treatment to each clinical situation. Recent results indicated that the plasma Flt3 ligand concentration was increased in patients suffering from either acquired or induced aplasia, suggesting that Flt3 ligand might be useful as a biological indicator of bone marrow status. We thus followed in a mouse model as well as in several clinical situations the variations in plasma Flt3 ligand concentration, after either homogeneous or heterogeneous irradiations. These variations were correlated to the number of hematopoietic progenitors and to other parameters such as duration and depth of pancytopenia. The results indicated that the concentration of Flt3 ligand in the blood reflects the bone marrow status, and that the follow-up of plasma Flt3 ligand concentration could give predictive information about the bone marrow function and the duration and severity of pancytopenia and thrombocytopenia. Nevertheless, the clinical use of Flt3 ligand as a biological indicator of bone marrow damage require the knowledge of the mechanisms regulating the variations in plasma Flt3 ligand concentration. We thus developed a study in the mouse model. The results indicated that the variations in plasma Flt3 ligand variations were not solely due to a balance between its production by lymphoid cells and its consumption by hematopoietic cells. Moreover, we showed that T lymphocytes are not the main regulator of plasma Flt3 ligand concentration as previously suggested, and that other cell types, possibly including bone marrow stromal cells, might be strongly implicated. These results also suggest that the Flt3 ligand is a main systemic regulator of hematopoiesis

  12. SOR-RING: an electron storage ring dedicated to spectroscopy, 2

    International Nuclear Information System (INIS)

    Kitamura, H.; Miyahara, T.; Sato, S.; Watanabe, M.; Mitani, S.

    1976-01-01

    A 300 MeV electron storage ring to be used exclusively as a synchrotron radiation source for spectroscopy has been constructed in Institute for Nuclear Study (INS), University of Tokyo, Tanashi. Its useful spectral range lies between 40 and 2200 A. The 1.3 GeV electron synchrotron of INS currently being operated for high energy particle experiments serves as an injector. Electron beams are extracted from the synchrotron at 300 MeV, transported about twenty meters, and injected to the ring one pulse per second. In the test operation a current of 10 mA was stored with a lifetime of one hour, while the design goal determined by the Touschek effect is 100 mA with one hour, for operation in 300 MeV. Increase of operating energy up to 375 MeV is feasible with a minor modification of the present design. (auth.)

  13. In silico identification of anthropogenic chemicals as ligands of zebrafish sex hormone binding globulin

    International Nuclear Information System (INIS)

    Thorsteinson, Nels; Ban, Fuqiang; Santos-Filho, Osvaldo; Tabaei, Seyed M.H.; Miguel-Queralt, Solange; Underhill, Caroline; Cherkasov, Artem; Hammond, Geoffrey L.

    2009-01-01

    Anthropogenic compounds with the capacity to interact with the steroid-binding site of sex hormone binding globulin (SHBG) pose health risks to humans and other vertebrates including fish. Building on studies of human SHBG, we have applied in silico drug discovery methods to identify potential binders for SHBG in zebrafish (Danio rerio) as a model aquatic organism. Computational methods, including; homology modeling, molecular dynamics simulations, virtual screening, and 3D QSAR analysis, successfully identified 6 non-steroidal substances from the ZINC chemical database that bind to zebrafish SHBG (zfSHBG) with low-micromolar to nanomolar affinities, as determined by a competitive ligand-binding assay. We also screened 80,000 commercial substances listed by the European Chemicals Bureau and Environment Canada, and 6 non-steroidal hits from this in silico screen were tested experimentally for zfSHBG binding. All 6 of these compounds displaced the [ 3 H]5α-dihydrotestosterone used as labeled ligand in the zfSHBG screening assay when tested at a 33 μM concentration, and 3 of them (hexestrol, 4-tert-octylcatechol, and dihydrobenzo(a)pyren-7(8H)-one) bind to zfSHBG in the micromolar range. The study demonstrates the feasibility of large-scale in silico screening of anthropogenic compounds that may disrupt or highjack functionally important protein:ligand interactions. Such studies could increase the awareness of hazards posed by existing commercial chemicals at relatively low cost

  14. Recent improvements to Binding MOAD: a resource for protein–ligand binding affinities and structures

    Science.gov (United States)

    Ahmed, Aqeel; Smith, Richard D.; Clark, Jordan J.; Dunbar, James B.; Carlson, Heather A.

    2015-01-01

    For over 10 years, Binding MOAD (Mother of All Databases; http://www.BindingMOAD.org) has been one of the largest resources for high-quality protein–ligand complexes and associated binding affinity data. Binding MOAD has grown at the rate of 1994 complexes per year, on average. Currently, it contains 23 269 complexes and 8156 binding affinities. Our annual updates curate the data using a semi-automated literature search of the references cited within the PDB file, and we have recently upgraded our website and added new features and functionalities to better serve Binding MOAD users. In order to eliminate the legacy application server of the old platform and to accommodate new changes, the website has been completely rewritten in the LAMP (Linux, Apache, MySQL and PHP) environment. The improved user interface incorporates current third-party plugins for better visualization of protein and ligand molecules, and it provides features like sorting, filtering and filtered downloads. In addition to the field-based searching, Binding MOAD now can be searched by structural queries based on the ligand. In order to remove redundancy, Binding MOAD records are clustered in different families based on 90% sequence identity. The new Binding MOAD, with the upgraded platform, features and functionalities, is now equipped to better serve its users. PMID:25378330

  15. Recent improvements to Binding MOAD: a resource for protein-ligand binding affinities and structures.

    Science.gov (United States)

    Ahmed, Aqeel; Smith, Richard D; Clark, Jordan J; Dunbar, James B; Carlson, Heather A

    2015-01-01

    For over 10 years, Binding MOAD (Mother of All Databases; http://www.BindingMOAD.org) has been one of the largest resources for high-quality protein-ligand complexes and associated binding affinity data. Binding MOAD has grown at the rate of 1994 complexes per year, on average. Currently, it contains 23,269 complexes and 8156 binding affinities. Our annual updates curate the data using a semi-automated literature search of the references cited within the PDB file, and we have recently upgraded our website and added new features and functionalities to better serve Binding MOAD users. In order to eliminate the legacy application server of the old platform and to accommodate new changes, the website has been completely rewritten in the LAMP (Linux, Apache, MySQL and PHP) environment. The improved user interface incorporates current third-party plugins for better visualization of protein and ligand molecules, and it provides features like sorting, filtering and filtered downloads. In addition to the field-based searching, Binding MOAD now can be searched by structural queries based on the ligand. In order to remove redundancy, Binding MOAD records are clustered in different families based on 90% sequence identity. The new Binding MOAD, with the upgraded platform, features and functionalities, is now equipped to better serve its users. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. Effects of electrostatic interactions on ligand dissociation kinetics

    Science.gov (United States)

    Erbaş, Aykut; de la Cruz, Monica Olvera; Marko, John F.

    2018-02-01

    We study unbinding of multivalent cationic ligands from oppositely charged polymeric binding sites sparsely grafted on a flat neutral substrate. Our molecular dynamics simulations are suggested by single-molecule studies of protein-DNA interactions. We consider univalent salt concentrations spanning roughly a 1000-fold range, together with various concentrations of excess ligands in solution. To reveal the ionic effects on unbinding kinetics of spontaneous and facilitated dissociation mechanisms, we treat electrostatic interactions both at a Debye-Hückel (DH) (or implicit ions, i.e., use of an electrostatic potential with a prescribed decay length) level and by the more precise approach of considering all ionic species explicitly in the simulations. We find that the DH approach systematically overestimates unbinding rates, relative to the calculations where all ion pairs are present explicitly in solution, although many aspects of the two types of calculation are qualitatively similar. For facilitated dissociation (FD) (acceleration of unbinding by free ligands in solution) explicit-ion simulations lead to unbinding at lower free-ligand concentrations. Our simulations predict a variety of FD regimes as a function of free-ligand and ion concentrations; a particularly interesting regime is at intermediate concentrations of ligands where nonelectrostatic binding strength controls FD. We conclude that explicit-ion electrostatic modeling is an essential component to quantitatively tackle problems in molecular ligand dissociation, including nucleic-acid-binding proteins.

  17. Database of ligand-induced domain movements in enzymes

    Directory of Open Access Journals (Sweden)

    Hayward Steven

    2009-03-01

    Full Text Available Abstract Background Conformational change induced by the binding of a substrate or coenzyme is a poorly understood stage in the process of enzyme catalysed reactions. For enzymes that exhibit a domain movement, the conformational change can be clearly characterized and therefore the opportunity exists to gain an understanding of the mechanisms involved. The development of the non-redundant database of protein domain movements contains examples of ligand-induced domain movements in enzymes, but this valuable data has remained unexploited. Description The domain movements in the non-redundant database of protein domain movements are those found by applying the DynDom program to pairs of crystallographic structures contained in Protein Data Bank files. For each pair of structures cross-checking ligands in their Protein Data Bank files with the KEGG-LIGAND database and using methods that search for ligands that contact the enzyme in one conformation but not the other, the non-redundant database of protein domain movements was refined down to a set of 203 enzymes where a domain movement is apparently triggered by the binding of a functional ligand. For these cases, ligand binding information, including hydrogen bonds and salt-bridges between the ligand and specific residues on the enzyme is presented in the context of dynamical information such as the regions that form the dynamic domains, the hinge bending residues, and the hinge axes. Conclusion The presentation at a single website of data on interactions between a ligand and specific residues on the enzyme alongside data on the movement that these interactions induce, should lead to new insights into the mechanisms of these enzymes in particular, and help in trying to understand the general process of ligand-induced domain closure in enzymes. The website can be found at: http://www.cmp.uea.ac.uk/dyndom/enzymeList.do

  18. Calculation of protein-ligand binding affinities.

    Science.gov (United States)

    Gilson, Michael K; Zhou, Huan-Xiang

    2007-01-01

    Accurate methods of computing the affinity of a small molecule with a protein are needed to speed the discovery of new medications and biological probes. This paper reviews physics-based models of binding, beginning with a summary of the changes in potential energy, solvation energy, and configurational entropy that influence affinity, and a theoretical overview to frame the discussion of specific computational approaches. Important advances are reported in modeling protein-ligand energetics, such as the incorporation of electronic polarization and the use of quantum mechanical methods. Recent calculations suggest that changes in configurational entropy strongly oppose binding and must be included if accurate affinities are to be obtained. The linear interaction energy (LIE) and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) methods are analyzed, as are free energy pathway methods, which show promise and may be ready for more extensive testing. Ultimately, major improvements in modeling accuracy will likely require advances on multiple fronts, as well as continued validation against experiment.

  19. Constitutive and ligand-induced TCR degradation

    DEFF Research Database (Denmark)

    von Essen, Marina; Bonefeld, Charlotte Menné; Siersma, Volkert

    2004-01-01

    Modulation of TCR expression levels is a central event during T cell development and activation, and it probably plays an important role in adjusting T cell responsiveness. Conflicting data have been published on down-regulation and degradation rates of the individual TCR subunits, and several di...... to the lysosomes. Similar results were obtained in studies of primary human Vbeta8+ T cells stimulated with superantigen. Based on these results, the simplest model for TCR internalization, sorting, and degradation is proposed.......Modulation of TCR expression levels is a central event during T cell development and activation, and it probably plays an important role in adjusting T cell responsiveness. Conflicting data have been published on down-regulation and degradation rates of the individual TCR subunits, and several...... divergent models for TCR down-regulation and degradation have been suggested. The aims of this study were to determine the rate constants for constitutive and ligand-induced TCR degradation and to determine whether the TCR subunits segregate or are processed as an intact unit during TCR down...

  20. The coordination chemistry of macrocyclic ligands II

    International Nuclear Information System (INIS)

    Klimes, J.; Knoechel, A.; Rudolph, G.

    1977-01-01

    Compounds of UO 2 (NO 3 ) 2 .6H 2 0 or Th(NO 3 ) 4 .5H 2 0 with five selected crown ethers were prepared according to the method described in Knoeckel et al., Inorg.Nucl.Chem.Lett.; 11:787 (1975). The products were characterized by chemical analysis, NMR, IR and Raman spectroscopy. The results are analyzed and discussed. It is shown that the NO 3 groups remain free after combination, and the H 2 0 groups form the bonds to the polyether. It is concluded that the polyether molecule is attached to two units of UO 2 (NO 3 ) 2 .2H 2 0 (or Th(NO 3 ) 4 .3H 2 0), one each side of the polyether. This would be contrary to the assumption in previous publications, that the U0 2 2+ and Th 4+ ions were coordinated inside the macrocyclic ligand structure. The present hypothesis, however, agrees with a recently published x-ray structure for the uranium compound. In view of the new proposed structure it is suggested that the compounds should be regarded as adducts rather than complexes. (U.K.)

  1. Complexes of technetium with polyhydric ligands

    International Nuclear Information System (INIS)

    Hwang, L.L.Y.; Ronca, N.; Solomon, N.A.; Steigman, J.

    1985-01-01

    Polyhydric complexes of Tc(V) show absorption bands near 500 nm, with molar absorptivity coefficients of about 100. The shorter-chain compounds like ethylene glycol produce complexes which quickly disproportionate to Tc(IV) (as TcO 2 ) and Tc(VII) (as TcO 4 - ) on acidification. The longer-chain ligands like mannitol and gluconate do not. However, while the mannitol complex shows no change in spectrum from pH 12 to pH 3, the gluconate and glucoheptonate compounds show a definite spectral change on acidification, starting at pH 5. Electrophoresis similarity showed a change in mobility with pH for Tc-glucoheptonate, but none for Tc-mannitol. It was concluded that the carboxylic acid group of glucoheptonate was not binding the technetium. In 25 molal choline chloride the glucoheptonate-Tc mole ratio was 1:1 or less. A similar result emerged from a similar experiment in methylcellosolve as solvent. (author)

  2. Solid state structure of thorium(IV) complexes with common aminopoly-carboxylate ligands

    International Nuclear Information System (INIS)

    Thuery, Pierre

    2011-01-01

    The crystal structures of the complexes formed by reaction of thorium(IV) nitrate with iminodiacetic acid (H 2 IDA), nitrilotriacetic acid (H 3 NTA), and ethylenediaminetetraacetic acid (H 4 EDTA) under hydrothermal conditions are reported. In [Th(HIDA) 2 (C 2 O 4 )].H 2 O (1), the metal atom is chelated by two carboxylate groups from two HIDA - anions and by two oxalate ligands formed in situ; two additional oxygen atoms from two more HIDA - anions complete the ten-coordinate environment of bi-capped square anti-prismatic geometry. The uncoordinated nitrogen atom is protonated and involved in hydrogen bonding. Two different ligands are present in [Th(NTA)(H 2 NTA)(H 2 O)].H 2 O (2), one of them being a O 3 ,N-chelating tri-anion which acts also as a bridge toward two neighboring metal ions, and the other being a bis-monodentate bridging species with an uncoordinated carboxylic arm and a central ammonium group. An aqua ligand completes the nine-coordinated, capped square anti-prismatic metal environment. The EDTA 4- anion in [Th(EDTA)(H 2 O)].2H 2 O (3) is chelating through one oxygen atom from each carboxylate group and the two nitrogen atoms, as in a previously reported molecular complex. Two carboxylate groups are bridging, which, with the addition of an aqua ligand, gives a capped square anti-prismatic coordination polyhedron. Aminopoly-carboxylate ligands have been much investigated in relation with actinide decorporation and nuclear wastes management studies, and the present results add to the structural information available on their complexes with thorium(IV), which has mainly been obtained up to now by extended X-ray absorption fine structure (EXAFS) spectroscopy. In particular, the bridging (non-chelating) coordination mode of H 2 NTA - is a novel feature in this context. All three complexes crystallize as two-dimensional assemblies and are thus novel examples of thorium-organic coordination polymers. (author)

  3. Electrolytic formation of technetium complexes with π-acceptor ligands

    International Nuclear Information System (INIS)

    Cerda, F.; Kremer, C.; Gambino, D.; Kremer, E.

    1994-01-01

    Electrolytic reduction of pertechnetate was performed in aqueous solution containing π-acceptor ligands. Cyanide and 1,10-phenanthroline were the selected ligands. In both cases, electrolyses produced a cathodic TcO 2 deposit and soluble Tc complexes. When cyanide was the ligand, the complexes formed were [Tc(CN) 6 ] 5- and [TcO 2 (CN) 4 ] 3- . When working with the amine, [Tc(phen) 3 ] 2+ and another positively charged species were found after reaction. Results are compared with previous studies with amines, and the usefulness of the electrolytic route to obtain Tc complexes is evaluated. (author) 11 refs.; 2 figs.; 1 tab

  4. Synthesis and study of new oxazoline-based ligands

    OpenAIRE

    Tilliet, Mélanie

    2008-01-01

    This thesis deals with the study of oxazoline-based ligands in metal-catalyzed asymmetric reactions. The first part describes the synthesis of six new bifunctinal pyridine-bis(oxazoline) ligands and their applications in asymmetric metal-catalysis. These ligands, in addition to a Lewis acid coordination site, are equipped with a Lewis basic part in the 4-position of the oxazoline rings. Dual activation by means of this system was probed in cyanide addition to aldehydes. The second part is con...

  5. NKG2D and its ligands in cancer.

    Science.gov (United States)

    Dhar, Payal; Wu, Jennifer D

    2018-04-01

    NKG2D is an activating immune receptor expressed by NK and effector T cells. Induced expression of NKG2D ligand on tumor cell surface during oncogenic insults renders cancer cells susceptible to immune destruction. In advanced human cancers, tumor cells shed NKG2D ligand to produce an immune soluble form as a means of immune evasion. Soluble NKG2D ligands have been associated with poor clinical prognosis in cancer patients. Harnessing NKG2D pathway is considered a viable avenue in cancer immunotherapy over recent years. In this review, we will discuss the progress and perspectives. Copyright © 2018. Published by Elsevier Ltd.

  6. Entangled zinc-ditetrazolate frameworks involving in situ ligand synthesis and topological modulation by various secondary N-donor ligands

    International Nuclear Information System (INIS)

    Li Yunwu; Chen Weilin; Wang Yonghui; Li Yangguang; Wang Enbo

    2009-01-01

    The introduction of various secondary N-donor ligands into an in situ ditetrazolate-ligand synthesis system of terephthalonitrile, NaN 3 and ZnCl 2 led to the formation of three new entangled frameworks Zn(pdtz)(4,4'-bipy).3H 2 O (1), [Zn(pdtz)(bpp)] 2 .3H 2 O (2) and Zn(pdtz) 0.5 (N 3 )(2,2'-bipy) (3) (4,4'-bipy=4,4'-bipyridine; bpp=1,3-bis(4-pyridyl)propane; 2,2'-bipy=2,2'-bipyridine; H 2 pdtz=5,5'-1,4-phenylene-ditetrazole). The formation of pdtz 2- ligand involves the Sharpless [2+3] cycloaddition reaction between terephthalonitrile and NaN 3 in the presence of Zn 2+ ion as a Lewis-acid catalyst under hydrothermal conditions. Compound 1 exhibits a fivefold interpenetrating 3D framework based on the diamondoid topology. Compound 2 displays a twofold parallel interpenetrating framework based on the wavelike individual network. Compound 3 possesses a 2D puckered network. These new Zn-ditetrazolate frameworks are highly dependent on the modulation of different secondary N-donor ligands. Their luminescent properties were investigated. - Graphical abstract: Three new entangled frameworks were prepared by an in situ ditetrazolate-ligand synthesis system assisted with various auxiliary N-donor ligands. The entangled structures can be modulated by different secondary ligands.

  7. Formation of mixed ligand complexes of UO22+ involving some nitrogen and oxygen donor ligands

    International Nuclear Information System (INIS)

    Singh, Mamta; Ram Nayan

    1996-01-01

    The complexation reactions of UO 2 2+ ion with nitrogen and oxygen donor ligands, 1-amino-2-naphthol-4-sulphonic acid, o-aminophenol (ap), 2-hydroxybenzoic acid (sa), 3-carboxy-4-hydroxybenzenesulphonic acid (ss) and 1,2-dihydroxybenzene (ca) have been investigated in aqueous solution employing the pH-titration technique. Analysis of the experimental data recorded at 25 degC and at an ionic strength of 0.10 M KNO 3 indicates formation of binary, hydroxo and ternary complexes of uranium. Formation constant values of the existing species have been evaluated and the results have been discussed. (author). 21 refs., 2 figs., 2 tabs

  8. Cytotoxicity of an 125I-labelled DNA ligand

    International Nuclear Information System (INIS)

    Karagiannis, T.C.; Lobachevsky, P.N.; Martin, R.F.

    2000-01-01

    The subcellular distribution and cytotoxicity of a DNA-binding ligand [ 125 I]-Hoechst 33258 following incubation of K562 cells with the drug was investigated. The ability of a radical scavenger, dimethyl sulphoxide, to protect cells from the 125 I-decay induced cell death was also studied. Three different concentrations and specific activities of the drug were used to provide different ligand : DNA binding ratios. The results demonstrated a trend toward improved delivery of the ligand to the nucleus and to chromatin at higher ligand concentrations, with concomitant increased sensitivity to 125 I-decay induced cytotoxicity and decreased protection by dimethyl sulphoxide. This correlation of radiobiological parameters with subcellular drug distribution is consistent with the classical dogma that attributes cytotoxicity to DNA double-stranded breakage in the vicinity of the site of decay, where the high LET nature of the damage confers minimal sensitivity to radical scavenging

  9. Epibatidine-derivatives: ligands for the neuronal nicotinic acetylcholine receptor

    International Nuclear Information System (INIS)

    Westera, G.; Patt, J.T.; Jankowski, K.; Bertrand, D.; Spang, J.; Schubiger, P.A.

    1997-01-01

    Epibatidine, isolated from the Ecuadorian frog Epipedobates tricolar, has been synthesized. 11 C-N-methyl derivate is investigated as useful nicotinergic receptor ligand by electrophysiological methods and in vivo mice experiments. (author) 2 figs., 7 refs

  10. PET and Hormone Receptor Ligands in Breast Cancer

    National Research Council Canada - National Science Library

    Gemignani, Mary

    2006-01-01

    .... To investigate this further, this project's objectives are: To evaluate the use of estrogen-like ligands labeled with positron emitters in preoperatively determining the ER status of breast cancer using PET...

  11. Unique advantages of organometallic supporting ligands for uranium complexes

    Energy Technology Data Exchange (ETDEWEB)

    Diaconescu, Paula L. [Univ. of California, Los Angeles, CA (United States); Garcia, Evan [Univ. of California, Los Angeles, CA (United States)

    2014-05-31

    The objective of our research project was to study the reactivity of uranium complexes supported by ferrocene-based ligands. In addition, this research provides training of graduate students as the next generation of actinide scientists.

  12. Unique advantages of organometallic supporting ligands for uranium complexes

    International Nuclear Information System (INIS)

    Diaconescu, Paula L.; Garcia, Evan

    2014-01-01

    The objective of our research project was to study the reactivity of uranium complexes supported by ferrocene-based ligands. In addition, this research provides training of graduate students as the next generation of actinide scientists.

  13. Ligand Binding Domain Protein in Tetracycline-Inducible Expression ...

    African Journals Online (AJOL)

    binding domain proteins in E. coli using a tetracycline inducible system. To allow for ... development of molecular ligands with improved therapeutic windows. Keywords: Nuclear receptor ..... functional recombinant cannabinoid receptor CB2 in ...

  14. related apoptosis-inducing ligand in transplastomic tobacco

    African Journals Online (AJOL)

    -inducing ligand (sTRAIL) can, as the whole length TRAIL protein, bind with its receptors and specifically induce the apoptosis of cancer cells; therefore, it has been developed as a potential therapeutic agent for various cancer treatments.

  15. Dysprosium complexes with the tetraphenylporphyrin macrocyclic ligand

    International Nuclear Information System (INIS)

    Martinez M, V.; Padilla, J.; Ramirez, F.M.

    1992-04-01

    In this report, the results obtained on the synthesis, characterization and study of the chemical behavior of dysprosium complex with the acetylacetone chelating agent (Hacac) and the tetraphenylporphyrin macrocyclic ligand (H 2 TFP) are given. Based on the literature but according to our necessities and interest, the appropriate methodology settled down from the synthesis of prime matters until the obtaining and characterization of the products. The acetyl acetonate complex was obtained of mono hydrated dysprosium [Dy(acac) 3 . H 2 0] and trihydrated [Dy(acac) 3 .3 H 2 0], the mono tetra phenyl porphyrinate [Dy(TFP)(acac). 2 ac] the double sandwich of the dysprosium porphyrinate [Dy(TFP) 2 ] and the triple sandwich of the dysprosium porphyrinate [Dy(TFP) 3 . 2 TCB] (TCB = trichlorobenzene). Its were characterized by their melting points, solubility, IR, UV, TGA and DTA both first and besides the techniques already mentioned for NMR'H, RPE and Magnetic susceptibility the three last complexes. From the spectroscopic point of view, IR and RPE its suggested the existence of a complex of inverse mixed valence [Dy(TFP) 2- (TFP) 1- ] for the Dy(TFP) 2 as a result of the existence of the free radical (TFP' 1- and that it was not in none of the other porphyrin compounds. In the NMR'H spectra of the compounds were not observed signals in the region from 0 to 10 ppm that which shows that the dysprosium complexes in special those of the porphyrin type are highly paramagnetic and its could be used as displacement reagents, creators of images and contrast agents of great utility in these days in studies of NMR, technique today by today used in medical diagnoses. (Author)

  16. Tetrapyrroles as Endogenous TSPO Ligands in Eukaryotes and Prokaryotes: Comparisons with Synthetic Ligands

    Directory of Open Access Journals (Sweden)

    Leo Veenman

    2016-06-01

    Full Text Available The 18 kDa translocator protein (TSPO is highly 0conserved in eukaryotes and prokaryotes. Since its discovery in 1977, numerous studies established the TSPO’s importance for life essential functions. For these studies, synthetic TSPO ligands typically are applied. Tetrapyrroles present endogenous ligands for the TSPO. Tetrapyrroles are also evolutionarily conserved and regulate multiple functions. TSPO and tetrapyrroles regulate each other. In animals TSPO-tetrapyrrole interactions range from effects on embryonic development to metabolism, programmed cell death, response to stress, injury and disease, and even to life span extension. In animals TSPOs are primarily located in mitochondria. In plants TSPOs are also present in plastids, the nuclear fraction, the endoplasmic reticulum, and Golgi stacks. This may contribute to translocation of tetrapyrrole intermediates across organelles’ membranes. As in animals, plant TSPO binds heme and protoporphyrin IX. TSPO-tetrapyrrole interactions in plants appear to relate to development as well as stress conditions, including salt tolerance, abscisic acid-induced stress, reactive oxygen species homeostasis, and finally cell death regulation. In bacteria, TSPO is important for switching from aerobic to anaerobic metabolism, including the regulation of photosynthesis. As in mitochondria, in bacteria TSPO is located in the outer membrane. TSPO-tetrapyrrole interactions may be part of the establishment of the bacterial-eukaryote relationships, i.e., mitochondrial-eukaryote and plastid-plant endosymbiotic relationships.

  17. A new class of modular chiral ligands with fluxional groups.

    Science.gov (United States)

    Sibi, Mukund P; Zhang, Ruzhou; Manyem, Shankar

    2003-08-06

    In ligand design for asymmetric catalysis, the usual norm is to derive the face shielding elements from a chiral source. New ligands in which the face shielding is determined by fluxional groups are introduced. Their design, modular synthesis, and experiments to demonstrate the significance of the fluxional groups are discussed. The advantage is that the fluxional groups, introduced at a later stage, allow for simple tuning of the face shielding group.

  18. Reversible Size Control of Silver Nanoclusters via Ligand-exchange

    KAUST Repository

    Bootharaju, Megalamane Siddaramappa

    2015-05-21

    The properties of atomically monodisperse noble metal nanoclusters (NCs) are intricately intertwined with their precise molecular formula. The vast majority of size-specific NC syntheses start from the reduction of the metal salt and thiol ligand mixture. Only in gold was it recently shown that ligand-exchange could induce the growth of NCs from one atomically precise species to another; a process of yet unknown reversibility. Here, we present a process for the ligand-exchange-induced growth of atomically precise silver NCs, in a biphasic liquid-liquid system, which is particularly of interest because of its complete reversibility and ability to occur at room temperature. We explore this phenomenon in-depth using Ag35(SG)18 [SG= glutathionate] and Ag44(4-FTP)30 [4-FTP= 4-fluorothiophenol] as model systems. We show that the ligand-exchange conversion of Ag35(SG)18 into Ag44(4-FTP)30 is rapid (< 5 min) and direct, while the reverse process proceeds slowly through intermediate cluster sizes. We adapt a recently developed theory of reverse Ostwald ripening to model the NCs’ interconvertibility. The model’s predictions are in good agreement with the experimental observations, and they highlight the importance of small changes in the ligand-metal binding energy in determining the final equilibrium NC size. Based on the insight provided by this model, we demonstrated experimentally that by varying the choice of ligands, ligand-exchange can be used to obtain different sized NCs. The findings in this work establish ligand-exchange as a versatile tool for tuning cluster sizes.

  19. Ligand-promoted protein folding by biased kinetic partitioning.

    Science.gov (United States)

    Hingorani, Karan S; Metcalf, Matthew C; Deming, Derrick T; Garman, Scott C; Powers, Evan T; Gierasch, Lila M

    2017-04-01

    Protein folding in cells occurs in the presence of high concentrations of endogenous binding partners, and exogenous binding partners have been exploited as pharmacological chaperones. A combined mathematical modeling and experimental approach shows that a ligand improves the folding of a destabilized protein by biasing the kinetic partitioning between folding and alternative fates (aggregation or degradation). Computationally predicted inhibition of test protein aggregation and degradation as a function of ligand concentration are validated by experiments in two disparate cellular systems.

  20. Ligand assisted cleavage of uranium oxo-clusters

    Energy Technology Data Exchange (ETDEWEB)

    Nocton, Gregory; Pecaut, Jacques; Mazzanti, Marinella [Laboratoire de Reconnaissance Ionique et Chimie de Coordination, Service de Chimie Inorganique et Biologique, UMR-E 3 CEA-UJF, CEA/DSM/INAC, CEA-Grenoble, 38054 Grenoble, Cedex 09 (France); Filinchuk, Yaroslav [Swiss Norwegian Beam Lines (SNBL) at the European Synchrotron Radiation Facility (ESRF), rue Jules Horowitz, 38043 Grenoble (France)

    2010-07-01

    Dibenzoylmethanate replaces the bridging triflate ligands in uranium triflate poly-oxo-clusters and cleaves the U{sub 12}O{sub 20} core yielding the new [U{sub 6}O{sub 4}(OH){sub 4}({eta}-dbm){sub 12}] dibenzoylmethanate (dbm{sup -}) cluster which slowly dissociates into a monomeric complex. This reactivity demonstrates the importance of bridging ligands in stabilizing uranium poly-oxo-clusters. (authors)

  1. Reversible Size Control of Silver Nanoclusters via Ligand-exchange

    KAUST Repository

    Bootharaju, Megalamane Siddaramappa; Burlakov, Victor M.; Besong, Tabot M.D.; Joshi, Chakra Prasad; AbdulHalim, L; Black, David; Whetten, Robert; Goriely, Alain; Bakr, Osman

    2015-01-01

    The properties of atomically monodisperse noble metal nanoclusters (NCs) are intricately intertwined with their precise molecular formula. The vast majority of size-specific NC syntheses start from the reduction of the metal salt and thiol ligand mixture. Only in gold was it recently shown that ligand-exchange could induce the growth of NCs from one atomically precise species to another; a process of yet unknown reversibility. Here, we present a process for the ligand-exchange-induced growth of atomically precise silver NCs, in a biphasic liquid-liquid system, which is particularly of interest because of its complete reversibility and ability to occur at room temperature. We explore this phenomenon in-depth using Ag35(SG)18 [SG= glutathionate] and Ag44(4-FTP)30 [4-FTP= 4-fluorothiophenol] as model systems. We show that the ligand-exchange conversion of Ag35(SG)18 into Ag44(4-FTP)30 is rapid (< 5 min) and direct, while the reverse process proceeds slowly through intermediate cluster sizes. We adapt a recently developed theory of reverse Ostwald ripening to model the NCs’ interconvertibility. The model’s predictions are in good agreement with the experimental observations, and they highlight the importance of small changes in the ligand-metal binding energy in determining the final equilibrium NC size. Based on the insight provided by this model, we demonstrated experimentally that by varying the choice of ligands, ligand-exchange can be used to obtain different sized NCs. The findings in this work establish ligand-exchange as a versatile tool for tuning cluster sizes.

  2. Models of protein–ligand crystal structures: trust, but verify

    Science.gov (United States)

    Deller, Marc C.

    2015-01-01

    X-ray crystallography provides the most accurate models of protein–ligand structures. These models serve as the foundation of many computational methods including structure prediction, molecular modelling, and structure-based drug design. The success of these computational methods ultimately depends on the quality of the underlying protein–ligand models. X-ray crystallography offers the unparalleled advantage of a clear mathematical formalism relating the experimental data to the protein–ligand model. In the case of X-ray crystallography, the primary experimental evidence is the electron density of the molecules forming the crystal. The first step in the generation of an accurate and precise crystallographic model is the interpretation of the electron density of the crystal, typically carried out by construction of an atomic model. The atomic model must then be validated for fit to the experimental electron density and also for agreement with prior expectations of stereochemistry. Stringent validation of protein–ligand models has become possible as a result of the mandatory deposition of primary diffraction data, and many computational tools are now available to aid in the validation process. Validation of protein–ligand complexes has revealed some instances of overenthusiastic interpretation of ligand density. Fundamental concepts and metrics of protein–ligand quality validation are discussed and we highlight software tools to assist in this process. It is essential that end users select high quality protein–ligand models for their computational and biological studies, and we provide an overview of how this can be achieved. PMID:25665575

  3. Metallogel formation in aqueous DMSO by perfluoroalkyl decorated terpyridine ligands.

    Science.gov (United States)

    Tatikonda, Rajendhraprasad; Bhowmik, Sandip; Rissanen, Kari; Haukka, Matti; Cametti, Massimo

    2016-08-09

    Terpyridine based ligands 1 and 2, decorated with a C8F17 perfluorinated tag, are able to form stable thermoreversible gels in the presence of several d-block metal chloride salts. The gel systems obtained have been characterized by NMR, X-ray diffraction, electron microscopies and Tgel experiments in order to gain insights into the observed different behaviour of the two similar ligands, also in terms of the effect of additional common anionic species.

  4. Solvothermal synthesis of tetravalent uranium with isophthalate or pyromellitate ligands

    Energy Technology Data Exchange (ETDEWEB)

    Falaise, Clement; Delille, Jason; Volkringer, Christophe; Loiseau, Thierry [Contribution from Unite de Catalyse et Chimie du Solide (UCCS) - UMR CNRS 8181, Universite de Lille, USTL-ENSCL, Villeneuve d' Ascq (France)

    2015-06-15

    Three new coordination polymers bearing tetravalent uranium have been isolated with the O-donor ligands such as isophthalate (1,3-bdc) or pyromellitate (btec). The compounds 1 and 3 have been solvothermally synthesized in N,N-dimethylformamide (DMF). The crystal structure of U(1,3-bdc){sub 2}(DMF) (1) is built up from discrete tricapped trigonal-primastic UO{sub 9} units, for which one carbonyl oxygen atom from DMF is bound to uranium. The connection of the UO{sub 9} units with the isophthalate linkers occurs in a chelating and bidentate fashion and gives rise to the formation of a 3D framework, delimiting narrow channels running along the [101] direction. Upon heating, the DMF molecules are removed, generating the second phase U(1,3-bdc){sub 2} (2) compound, closely related to 1. Indeed, the coordination environment of uranium is reduced to eight with a distorted square-antiprismatic geometry. This transition induces the relative shrinkage of the network (ΔV = 23 %). The structure of the compound U(btec)(DMF){sub 2} (3) also exhibits a 3D framework composed of an isolated bicapped square-antiprismatic UO{sub 10} unit, for which two carbonyl oxygen atoms from DMF are bonded to uranium. Pyromellitate ensures the connection of the UO{sub 10} units through the carboxylate arms in a chelating mode. This results in the formation of a network with diamond-shaped channels, developed along the c axis and encapsulating the DMF molecules. In contrast to 1, no stable phase is observed upon removing the DMF species by heating. (Copyright copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  5. Prediction of ligand effects in platinum-amyloid-β coordination.

    Science.gov (United States)

    Turner, Matthew; Deeth, Robert J; Platts, James A

    2017-08-01

    Ligand field molecular mechanics (LFMM) and semi-empirical Parametric Model 7 (PM7) methods are applied to a series of six Pt II -Ligand systems binding to the N-terminal domain of the amyloid-β (Aβ) peptide. Molecular dynamics using a combined LFMM/Assisted Model Building with Energy Refinement (AMBER) approach is used to explore the conformational freedom of the peptide fragment, and identifies favourable platinum binding modes and peptide conformations for each ligand investigated. Platinum coordination is found to depend on the nature of the ligand, providing evidence that binding mode may be controlled by suitable ligand design. Boltzmann populations at 310K indicate that each Pt-Aβ complex has a small number of thermodynamically accessible states. Ramachandran maps are constructed for the sampled Pt-Aβ conformations and secondary structural analysis of the obtained complex structures is performed and contrasted with the free peptide; coordination of these platinum complexes disrupts existing secondary structure in the Aβ peptide and promotes formation of ligand-specific turn-type secondary structure. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Ligand recognition by RAR and RXR receptors: binding and selectivity.

    Science.gov (United States)

    Sussman, Fredy; de Lera, Angel R

    2005-10-06

    Fundamental biological functions, most notably embriogenesis, cell growth, cell differentiation, and cell apoptosis, are in part regulated by a complex genomic network that starts with the binding (and activation) of retinoids to their cognate receptors, members of the superfamily of nuclear receptors. We have studied ligand recognition of retinoic receptors (RXRalpha and RARgamma) using a molecular-mechanics-based docking method. The protocol used in this work is able to rank the affinity of pairs of ligands for a single retinoid receptor, the highest values corresponding to those that adapt better to the shape of the binding site and generate the optimal set of electrostatic and apolar interactions with the receptor. Moreover, our studies shed light onto some of the energetic contributions to retinoid receptor ligand selectivity. In this regard we show that there is a difference in polarity between the binding site regions that anchor the carboxylate in RAR and RXR, which translates itself into large differences in the energy of interaction of both receptors with the same ligand. We observe that the latter energy change is canceled off by the solvation energy penalty upon binding. This energy compensation is borne out as well by experiments that address the effect of site-directed mutagenesis on ligand binding to RARgamma. The hypothesis that the difference in binding site polarity might be exploited to build RXR-selective ligands is tested with some compounds having a thiazolidinedione anchoring group.

  7. Predicting Efficient Antenna Ligands for Tb(III) Emission

    Energy Technology Data Exchange (ETDEWEB)

    Samuel, Amanda P.S.; Xu, Jide; Raymond, Kenneth

    2008-10-06

    A series of highly luminescent Tb(III) complexes of para-substituted 2-hydroxyisophthalamide ligands (5LI-IAM-X) has been prepared (X = H, CH{sub 3}, (C=O)NHCH{sub 3}, SO{sub 3}{sup -}, NO{sub 2}, OCH{sub 3}, F, Cl, Br) to probe the effect of substituting the isophthalamide ring on ligand and Tb(III) emission in order to establish a method for predicting the effects of chromophore modification on Tb(III) luminescence. The energies of the ligand singlet and triplet excited states are found to increase linearly with the {pi}-withdrawing ability of the substituent. The experimental results are supported by time-dependent density functional theory (TD-DFT) calculations performed on model systems, which predict ligand singlet and triplet energies within {approx}5% of the experimental values. The quantum yield ({Phi}) values of the Tb(III) complex increases with the triplet energy of the ligand, which is in part due to the decreased non-radiative deactivation caused by thermal repopulation of the triplet. Together, the experimental and theoretical results serve as a predictive tool that can be used to guide the synthesis of ligands used to sensitize lanthanide luminescence.

  8. The affinity plutonium(IV) for nitrogen donor ligands

    International Nuclear Information System (INIS)

    Jarvis, N.V.; Hancock, R.D.

    1994-01-01

    Established ligand design principles are used to predict the solution chemistry of Pu(IV) with nitrogen donor ligands which do not contain carboxylate donors. pK a 's of the nitrogen donors are lowered by addition of hydroxyalkyl groups causing Pu(IV) to have a greater affinity for these ligands than for hydroxide. Potentiometric studies using the ligands N,N,N'N',N''-pentakis(2-hydroxypropyl)-1,4,7-triazaheptane; N,N,N',N',N''-pentakis(2-hydroxyethyl)-1,4,7-triazaheptane; N,N,N',N',N'-tetrakis(2-hydroxyethyl)-1,2-diaminoethane; N,N,N',N'-tetrakis(2-hydroxyethyl)-trans-1,2-diaminocyclohexane; 1,4,8,11-tetrakis(2-hydroxyethyl)-1,4,8,11-tetraazacyclotetradecane and N,N-bis(2-hydroxyethyl)glycine with Pu(IV) showed that Pu(IV) has a considerable aqueous solution chemistry with these ligands. Data were processed by the ESTA library of programs and stability constants for all the systems are reported. Implications for selective ligand design for Pu(IV) are discussed. (orig.)

  9. A Ferrocene-Based Catecholamide Ligand: the Consequences of Ligand Swivel for Directed Supramolecular Self-Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Mugridge, Jeffrey; Fiedler, Dorothea; Raymond, Kenneth

    2010-02-04

    A ferrocene-based biscatecholamide ligand was prepared and investigated for the formation of metal-ligand supramolecular assemblies with different metals. Reaction with Ge(IV) resulted in the formation of a variety of Ge{sub n}L{sub m} coordination complexes, including [Ge{sub 2}L{sub 3}]{sup 4-} and [Ge{sub 2}L{sub 2}({mu}-OMe){sub 2}]{sup 2-}. The ligand's ability to swivel about the ferrocenyl linker and adopt different conformations accounts for formation of many different Ge{sub n}L{sub m} species. This study demonstrates why conformational ligand rigidity is essential in the rational design and directed self-assembly of supramolecular complexes.

  10. Secondary ligand-directed assembly of Co(II) coordination polymers based on a pyridine carboxylate ligand

    International Nuclear Information System (INIS)

    Cao, Ke-Li; Zhang, Yi-Ping; Cai, Yi-Ni; Xu, Xiao-Wei; Feng, Yun-Long

    2014-01-01

    To investigate the influence of hydrogen bonds and secondary ligands on the structures and properties of the resulting frameworks, five new Co(II) compounds have been synthesized by the reactions of Co(II) salts and 3,5-bis(pyridin-4-ylmethoxy)benzoic acid (HL) with four rationally selected dicarboxylic acid ligands. Without secondary ligand, we got one compound [CoL 2 (H 2 O) 2 ] n ·2nH 2 O (1), which possesses a 1D chain structure. In the presence of ancillary ligands, namely, 1,3-adamantanedicarboxylic acid (H 2 adbc), terephthalic acid (H 2 tpa), thiophene-2,5-dicarboxylic acid (H 2 tdc) and 1,4-benzenedithioacetic acid (H 2 bdtc), four 3D structures [Co 2 L 2 (adbc)] n ·nH 2 O (2), [Co 2 L 2 (tpa)] n (3), [Co 2 L 2 (tdc)] n (4), [Co 2 L 2 (bdtc)(H 2 O)] n (5) were obtained, respectively. It can be observed from the architectures of 1–5 that hydrogen bonds and secondary ligands both have great effects on the spatial connective fashions, resulting in the formation of various dimensional compounds. The XRPD, TGA data of title polymers and the magnetic properties for 2 and 5 have also been investigated. - Graphical abstract: The structural differences show that the ancillary ligands have great effects on the spatial connective fashions, resulting in the formation of various dimensional compounds. - Highlights: • Five new Co(II) coordination polymers have been synthesized by solvothermal reactions based on 3,5-bis(pyridin-4-ylmethoxy)benzoic acid (HL). • The long-flexible ligand (HL) is a good candidate to produce interpenetrating architectures. • The secondary dicarboxylic acid ligands play important roles in the spatial connective fashions and the formation of various dimensional compounds. • The magnetism studies show that both 2 and 5 exhibit antiferromagnetic interactions

  11. Effect of Ligand Field Tuning on the SMM Behavior for Three Related Alkoxide-Bridged Dysprosium Dimers.

    Science.gov (United States)

    Peng, Yan; Mereacre, Valeriu; Baniodeh, Amer; Lan, Yanhua; Schlageter, Martin; Kostakis, George E; Powell, Annie K

    2016-01-04

    The synthesis and characterization of three Dy2 compounds, [Dy2(HL1)2(NO3)4] (1), [Dy2(L2)2(NO3)4] (2), and [Dy2(HL3)2(NO3)4] (3), formed using related tripodal ligands with a central tertiary amine bearing picolyl and alkoxy arms, 2-[(2-hydroxy-ethyl)-pyridin-2-ylmethylamino]-ethanol (H2L1), 2-(bis-pyridin-2-ylmethylamino)-ethanol (HL2), and 2-(bis-pyridin-2-ylmethylamino)-propane-1,3-diol (H2L3), are reported. The compounds are rare examples of alkoxide-bridged {Dy2} complexes and display capped square antiprism coordination geometry around each Dy(III) ion. Changes in the ligand field environment around the Dy(III) ions brought about through variations in the ligand donors can be gauged from the magnetic properties, with compounds 1 and 2 showing antiparallel coupling between the Dy(III) ions and 3 showing parallel coupling. Furthermore, slow relaxation of the magnetization typical of SMM behavior could be observed for compounds 2 and 3, suggesting that small variations in the ligand field can have a significant influence on the slow relaxation processes responsible for SMM behavior of Dy(III)-based systems.

  12. Synthesis, Characterization, and Antibacterial Studies of Mixed Ligand Dioxouranium Complexes with 8-Hydroxyquinoline and Some Amino Acids

    Science.gov (United States)

    Patil, Sunil S.; Thakur, Ganesh A.; Shaikh, Manzoor M.

    2011-01-01

    Mixed ligand complexes of dioxouranium (VI) of the type [UO2(Q)(L)·2H2O] have been synthesized using 8-hydroxyquinoline (HQ) as a primary ligand and amino acids (HL) such as L-threonine, L-tryptophan, and L-isoleucine as secondary ligands. The metal complexes have been characterized by elemental analysis, electrical conductance, magnetic susceptibility measurements, and spectral and thermal studies. The electrical conductance studies of the complexes indicate their nonelectrolytic nature. Magnetic susceptibility measurements revealed diamagnetic nature of the complexes. Electronic absorption spectra of the complexes show intraligand and charge transfer transitions, respectively. Bonding of the metal ion through N- and O-donor atoms of the ligands is revealed by IR studies, and the chemical environment of the protons is confirmed by NMR studies. The thermal analysis data of the complexes indicate the presence of coordinated water molecules. The agar cup and tube dilution methods have been used to study the antibacterial activity of the complexes against the pathogenic bacteria S. aureus, C. diphtheriae, S. typhi, and E. coli. PMID:22389843

  13. Ligand-modulated interactions between charged monolayer-protected Au144 (SR)60 gold nanoparticles in physiological saline

    Science.gov (United States)

    Villarreal, Oscar; Chen, Liao; Whetten, Robert; Yacaman, Miguel

    2015-03-01

    We studied the interactions of functionalized Au144 nanoparticles (NPs) in a near-physiological environment through all-atom molecular dynamics simulations. The AuNPs were coated with a homogeneous selection of 60 thiolates: 11-mercapto-1-undecanesulfonate, 5-mercapto-1-pentanesulfonate, 5-mercapto-1-pentane-amine, 4-mercapto-benzoate or 4-mercapto-benzamide. These ligands were selected to elucidate how the aggregation behavior depends on the ligands' sign of charge, length, and flexibility. Simulating the dynamics of a pair of identical AuNPs in a cell of saline of 150 mM NaCl in addition to 120 Na+/Cl- counter-ions, we computed the aggregation affinities from the potential of mean force as a function of the pair separation. We found that NPs coated with negatively charged, short ligands have the strongest affinities mediated by multiple Na+ counter-ions residing on a plane in-between the pair and forming ``salt bridges'' to both NPs. Positively charged NPs have weaker affinities, as Cl counter-ions form fewer and weaker salt bridges. The longer ligands' large fluctuations disfavor the forming of salt bridges, enable hydrophobic contact between the exposed hydrocarbon chains and interact at greater separations due to the fact that the screening effect is rather incomplete. Supported by the CONACYT, NIH, NSF and TACC.

  14. Quantitative analysis of protein-ligand interactions by NMR.

    Science.gov (United States)

    Furukawa, Ayako; Konuma, Tsuyoshi; Yanaka, Saeko; Sugase, Kenji

    2016-08-01

    Protein-ligand interactions have been commonly studied through static structures of the protein-ligand complex. Recently, however, there has been increasing interest in investigating the dynamics of protein-ligand interactions both for fundamental understanding of the underlying mechanisms and for drug development. NMR is a versatile and powerful tool, especially because it provides site-specific quantitative information. NMR has widely been used to determine the dissociation constant (KD), in particular, for relatively weak interactions. The simplest NMR method is a chemical-shift titration experiment, in which the chemical-shift changes of a protein in response to ligand titration are measured. There are other quantitative NMR methods, but they mostly apply only to interactions in the fast-exchange regime. These methods derive the dissociation constant from population-averaged NMR quantities of the free and bound states of a protein or ligand. In contrast, the recent advent of new relaxation-based experiments, including R2 relaxation dispersion and ZZ-exchange, has enabled us to obtain kinetic information on protein-ligand interactions in the intermediate- and slow-exchange regimes. Based on R2 dispersion or ZZ-exchange, methods that can determine the association rate, kon, dissociation rate, koff, and KD have been developed. In these approaches, R2 dispersion or ZZ-exchange curves are measured for multiple samples with different protein and/or ligand concentration ratios, and the relaxation data are fitted to theoretical kinetic models. It is critical to choose an appropriate kinetic model, such as the two- or three-state exchange model, to derive the correct kinetic information. The R2 dispersion and ZZ-exchange methods are suitable for the analysis of protein-ligand interactions with a micromolar or sub-micromolar dissociation constant but not for very weak interactions, which are typical in very fast exchange. This contrasts with the NMR methods that are used

  15. Study of the stability of organic ligands usable for the spent nuclear fuel reprocessing

    International Nuclear Information System (INIS)

    Draye, Micheline

    1994-01-01

    The first part of this research thesis on the stability of organic ligands in radioactive environment, reports the study of the stability of the dicyclohexano-18-crown-6 (DCH18C6) in radioactive environment by using several analytical techniques (nuclear magnetic resonance or NMR, X-ray diffraction, Fourier transform infrared spectroscopy or FTIR, gas chromatography or GC, and coupled gas chromatography/mass spectroscopy). The seven main radiolysis products of DCH18C6 are identified and then synthesised to be tested in radioactive environment. These products are soluble in nitric medium, and partially precipitate plutonium, but cannot in any case disturb the reprocessing process based on a continuous extraction system. Chemical yields are computed and DCH18C6 appears to be a serious candidate for the reprocessing of spent nuclear fuels. The second part reports the study of the stability of the poly(4-vinylpyridine) or P4VP in radioactive environment. It appears that gamma radiations produce radicals in the P4VP which recombine in function of the irradiation dose. However, this material is very stable in acid environment and radioactive environment [fr

  16. Biotechnological Fluorescent Ligands of the Bradykinin B1 Receptor: Protein Ligands for a Peptide Receptor.

    Directory of Open Access Journals (Sweden)

    Xavier Charest-Morin

    Full Text Available The bradykinin (BK B1 receptor (B1R is a peculiar G protein coupled receptor that is strongly regulated to the point of being inducible in immunopathology. Limited clinical evidence suggests that its expression in peripheral blood mononuclear cells is a biomarker of active inflammatory states. In an effort to develop a novel imaging/diagnostic tool, we report the rational design and testing of a fusion protein that is a ligand of the human B1R but not likely to label peptidases. This ligand is composed of a fluorescent protein (FP (enhanced green FP [EGFP] or mCherry prolonged at its N-terminus by a spacer peptide and a classical peptide agonist or antagonist (des-Arg9-BK, [Leu8]des-Arg9-BK, respectively. The design of the spacer-ligand joint peptide was validated by a competition assay for [3H]Lys-des-Arg9-BK binding to the human B1R applied to 4 synthetic peptides of 18 or 19 residues. The labeling of B1R-expressing cells with EGFP or mCherry fused with 7 of such peptides was performed in parallel (microscopy. Both assays indicated that the best design was FP-(Asn-Glyn-Lys-des-Arg9-BK; n = 15 was superior to n = 5, suggesting benefits from minimizing steric hindrance between the FP and the receptor. Cell labeling concerned mostly plasma membranes and was inhibited by a B1R antagonist. EGFP-(Asn-Gly15-Lys-des-Arg9-BK competed for the binding of [3H]Lys-des-Arg9-BK to human recombinant B1R, being only 10-fold less potent than the unlabeled form of Lys-des-Arg9-BK to do so. The fusion protein did not label HEK 293a cells expressing recombinant human BK B2 receptors or angiotensin converting enzyme. This study identifies a modular C-terminal sequence that can be adapted to protein cargoes, conferring high affinity for the BK B1R, with possible applications in diagnostic cytofluorometry, histology and drug delivery (e.g., in oncology.

  17. Encapsulated environment

    NARCIS (Netherlands)

    McLellan, Tom M.; Daanen, Hein A M; Cheung, Stephen S.

    2013-01-01

    In many occupational settings, clothing must be worn to protect individuals from hazards in their work environment. However, personal protective clothing (PPC) restricts heat exchange with the environment due to high thermal resistance and low water vapor permeability. As a consequence, individuals

  18. Encapsulated Environment

    NARCIS (Netherlands)

    McLellan, T.M.; Daanen, H.A.M.; Cheung, S.S.

    2013-01-01

    In many occupational settings, clothing must be worn to protect individuals from hazards in their work environment. However, personal protective clothing (PPC) restricts heat exchange with the environment due to high thermal resistance and low water vapor permeability. As a consequence, individuals

  19. Essential role of conformational selection in ligand binding.

    Science.gov (United States)

    Vogt, Austin D; Pozzi, Nicola; Chen, Zhiwei; Di Cera, Enrico

    2014-02-01

    Two competing and mutually exclusive mechanisms of ligand recognition - conformational selection and induced fit - have dominated our interpretation of ligand binding in biological macromolecules for almost six decades. Conformational selection posits the pre-existence of multiple conformations of the macromolecule from which the ligand selects the optimal one. Induced fit, on the other hand, postulates the existence of conformational rearrangements of the original conformation into an optimal one that are induced by binding of the ligand. In the former case, conformational transitions precede the binding event; in the latter, conformational changes follow the binding step. Kineticists have used a facile criterion to distinguish between the two mechanisms based on the dependence of the rate of relaxation to equilibrium, kobs, on the ligand concentration, [L]. A value of kobs decreasing hyperbolically with [L] has been seen as diagnostic of conformational selection, while a value of kobs increasing hyperbolically with [L] has been considered diagnostic of induced fit. However, this simple conclusion is only valid under the rather unrealistic assumption of conformational transitions being much slower than binding and dissociation events. In general, induced fit only produces values of kobs that increase with [L] but conformational selection is more versatile and is associated with values of kobs that increase with, decrease with or are independent of [L]. The richer repertoire of kinetic properties of conformational selection applies to kinetic mechanisms with single or multiple saturable relaxations and explains the behavior of nearly all experimental systems reported in the literature thus far. Conformational selection is always sufficient and often necessary to account for the relaxation kinetics of ligand binding to a biological macromolecule and is therefore an essential component of any binding mechanism. On the other hand, induced fit is never necessary and

  20. Ligand-specific conformational changes in the alpha1 glycine receptor ligand-binding domain

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Lynch, Joseph W

    2009-01-01

    , and by the antagonist, strychnine. Voltage-clamp fluorometry involves labeling introduced cysteines with environmentally sensitive fluorophores and inferring structural rearrangements from ligand-induced fluorescence changes. In the inner beta-sheet, we labeled residues in loop 2 and in binding domain loops D and E....... At each position, strychnine and glycine induced distinct maximal fluorescence responses. The pre-M1 domain responded similarly; at each of four labeled positions glycine produced a strong fluorescence signal, whereas strychnine did not. This suggests that glycine induces conformational changes...... in the inner beta-sheet and pre-M1 domain that may be important for activation, desensitization, or both. In contrast, most labeled residues in loops C and F yielded fluorescence changes identical in magnitude for glycine and strychnine. A notable exception was H201C in loop C. This labeled residue responded...

  1. Microassay for measurement of binding of radiolabelled ligands to cell surface molecules

    International Nuclear Information System (INIS)

    Woof, J.M.; Burton, D.R.

    1988-01-01

    An improved technique for measuring the binding of radiolabelled ligands to cell surface molecules has been developed by modification of a procedure using centrifugation through a water-immiscible oil to separate free and cell-bound ligand. It maximises the percentage of ligand bound since cell-bound and free ligand can be separated easily and reproducibly even when very small reaction volumes are used. This permits low levels of ligand radiolabelling and relatively low numbers of cells to be used

  2. Using chemical shift perturbation to characterise ligand binding.

    Science.gov (United States)

    Williamson, Mike P

    2013-08-01

    Chemical shift perturbation (CSP, chemical shift mapping or complexation-induced changes in chemical shift, CIS) follows changes in the chemical shifts of a protein when a ligand is added, and uses these to determine the location of the binding site, the affinity of the ligand, and/or possibly the structure of the complex. A key factor in determining the appearance of spectra during a titration is the exchange rate between free and bound, or more specifically the off-rate koff. When koff is greater than the chemical shift difference between free and bound, which typically equates to an affinity Kd weaker than about 3μM, then exchange is fast on the chemical shift timescale. Under these circumstances, the observed shift is the population-weighted average of free and bound, which allows Kd to be determined from measurement of peak positions, provided the measurements are made appropriately. (1)H shifts are influenced to a large extent by through-space interactions, whereas (13)Cα and (13)Cβ shifts are influenced more by through-bond effects. (15)N and (13)C' shifts are influenced both by through-bond and by through-space (hydrogen bonding) interactions. For determining the location of a bound ligand on the basis of shift change, the most appropriate method is therefore usually to measure (15)N HSQC spectra, calculate the geometrical distance moved by the peak, weighting (15)N shifts by a factor of about 0.14 compared to (1)H shifts, and select those residues for which the weighted shift change is larger than the standard deviation of the shift for all residues. Other methods are discussed, in particular the measurement of (13)CH3 signals. Slow to intermediate exchange rates lead to line broadening, and make Kd values very difficult to obtain. There is no good way to distinguish changes in chemical shift due to direct binding of the ligand from changes in chemical shift due to allosteric change. Ligand binding at multiple sites can often be characterised, by

  3. New synthetic routes toward enantiopure nitrogen donor ligands.

    Science.gov (United States)

    Sala, Xavier; Rodríguez, Anna M; Rodríguez, Montserrat; Romero, Isabel; Parella, Teodor; von Zelewsky, Alexander; Llobet, Antoni; Benet-Buchholz, Jordi

    2006-12-08

    New polypyridylic chiral ligands, having either C3 or lower symmetry, have been prepared via a de novo construction of the pyridine nucleus by means of Kröhnke methodology in the key step. The chiral moieties of these ligands originate from the monoterpen chiral pool, namely (-)-alpha-pinene ((-)-14, (-)-15) and (-)-myrtenal ((-)-9, (-)-10). Extension of the above-mentioned asymmetric synthesis procedure to the preparation of enantiopure derivatives of some commonly used polypyridylic ligands has been achieved through a new aldehyde building block ((-)-16). As an example, the synthesis of a chiral derivative of N,N-bis(2-pyridylmethyl)ethylamine (bpea) ligand, (-)-19, has been performed to illustrate the viability of the method. The coordinative ability of the ligands has been tested through the synthesis and characterization of complexes [Mn((-)-19)Br2], (-)-20, and [RuCl((-)-10)(bpy)](BF4), (-)-21. Some preliminary results related to the enantioselective catalytic epoxidation of styrene with the ruthenium complex are also presented.

  4. A grand unified model for liganded gold clusters

    Science.gov (United States)

    Xu, Wen Wu; Zhu, Beien; Zeng, Xiao Cheng; Gao, Yi

    2016-12-01

    A grand unified model (GUM) is developed to achieve fundamental understanding of rich structures of all 71 liganded gold clusters reported to date. Inspired by the quark model by which composite particles (for example, protons and neutrons) are formed by combining three quarks (or flavours), here gold atoms are assigned three `flavours' (namely, bottom, middle and top) to represent three possible valence states. The `composite particles' in GUM are categorized into two groups: variants of triangular elementary block Au3(2e) and tetrahedral elementary block Au4(2e), all satisfying the duet rule (2e) of the valence shell, akin to the octet rule in general chemistry. The elementary blocks, when packed together, form the cores of liganded gold clusters. With the GUM, structures of 71 liganded gold clusters and their growth mechanism can be deciphered altogether. Although GUM is a predictive heuristic and may not be necessarily reflective of the actual electronic structure, several highly stable liganded gold clusters are predicted, thereby offering GUM-guided synthesis of liganded gold clusters by design.

  5. Receptor-ligand binding sites and virtual screening.

    Science.gov (United States)

    Hattotuwagama, Channa K; Davies, Matthew N; Flower, Darren R

    2006-01-01

    Within the pharmaceutical industry, the ultimate source of continuing profitability is the unremitting process of drug discovery. To be profitable, drugs must be marketable: legally novel, safe and relatively free of side effects, efficacious, and ideally inexpensive to produce. While drug discovery was once typified by a haphazard and empirical process, it is now increasingly driven by both knowledge of the receptor-mediated basis of disease and how drug molecules interact with receptors and the wider physiome. Medicinal chemistry postulates that to understand a congeneric ligand series, or set thereof, is to understand the nature and requirements of a ligand binding site. Likewise, structural molecular biology posits that to understand a binding site is to understand the nature of ligands bound therein. Reality sits somewhere between these extremes, yet subsumes them both. Complementary to rules of ligand design, arising through decades of medicinal chemistry, structural biology and computational chemistry are able to elucidate the nature of binding site-ligand interactions, facilitating, at both pragmatic and conceptual levels, the drug discovery process.

  6. Tuning Confinement in Colloidal Silicon Nanocrystals with Saturated Surface Ligands

    Energy Technology Data Exchange (ETDEWEB)

    Neale, Nathan R [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Carroll, Gerard [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Limpens, Rens [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2018-04-16

    The optical properties of silicon nanocrystals (Si NCs) are a subject of intense study and continued debate. In particular, Si NC photoluminescence (PL) properties are known to depend strongly on the surface chemistry, resulting in electron-hole recombination pathways derived from the Si NC band-edge, surface-state defects, or combined NC-conjugated ligand hybrid states. In this Letter, we perform a comparison of three different saturated surface functional groups - alkyls, amides, and alkoxides - on nonthermal plasma-synthesized Si NCs. We find a systematic and size-dependent high-energy (blue) shift in the PL spectrum of Si NCs with amide and alkoxy functionalization relative to alkyl. Time-resolved photoluminescence and transient absorption spectroscopies reveal no change in the excited-state dynamics between Si NCs functionalized with alkyl, amide, or alkoxide ligands, showing for the first time that saturated ligands - not only surface-derived charge-transfer states or hybridization between NC and low-lying ligand orbitals - are responsible for tuning the Si NC optical properties. To explain these PL shifts we propose that the atom bound to the Si NC surface strongly interacts with the Si NC electronic wave function and modulates the Si NC quantum confinement. These results reveal a potentially broadly applicable correlation between the optoelectronic properties of Si NCs and related quantum-confined structures based on the interaction between NC surfaces and the ligand binding group.

  7. Tuning Confinement in Colloidal Silicon Nanocrystals with Saturated Surface Ligands.

    Science.gov (United States)

    Carroll, Gerard M; Limpens, Rens; Neale, Nathan R

    2018-05-09

    The optical properties of silicon nanocrystals (Si NCs) are a subject of intense study and continued debate. In particular, Si NC photoluminescence (PL) properties are known to depend strongly on the surface chemistry, resulting in electron-hole recombination pathways derived from the Si NC band-edge, surface-state defects, or combined NC-conjugated ligand hybrid states. In this Letter, we perform a comparison of three different saturated surface functional groups-alkyls, amides, and alkoxides-on nonthermal plasma-synthesized Si NCs. We find a systematic and size-dependent high-energy (blue) shift in the PL spectrum of Si NCs with amide and alkoxy functionalization relative to alkyl. Time-resolved photoluminescence and transient absorption spectroscopies reveal no change in the excited-state dynamics between Si NCs functionalized with alkyl, amide, or alkoxide ligands, showing for the first time that saturated ligands-not only surface-derived charge-transfer states or hybridization between NC and low-lying ligand orbitals-are responsible for tuning the Si NC optical properties. To explain these PL shifts we propose that the atom bound to the Si NC surface strongly interacts with the Si NC electronic wave function and modulates the Si NC quantum confinement. These results reveal a potentially broadly applicable correlation between the optoelectronic properties of Si NCs and related quantum-confined structures based on the interaction between NC surfaces and the ligand binding group.

  8. Cloud computing for protein-ligand binding site comparison.

    Science.gov (United States)

    Hung, Che-Lun; Hua, Guan-Jie

    2013-01-01

    The proteome-wide analysis of protein-ligand binding sites and their interactions with ligands is important in structure-based drug design and in understanding ligand cross reactivity and toxicity. The well-known and commonly used software, SMAP, has been designed for 3D ligand binding site comparison and similarity searching of a structural proteome. SMAP can also predict drug side effects and reassign existing drugs to new indications. However, the computing scale of SMAP is limited. We have developed a high availability, high performance system that expands the comparison scale of SMAP. This cloud computing service, called Cloud-PLBS, combines the SMAP and Hadoop frameworks and is deployed on a virtual cloud computing platform. To handle the vast amount of experimental data on protein-ligand binding site pairs, Cloud-PLBS exploits the MapReduce paradigm as a management and parallelizing tool. Cloud-PLBS provides a web portal and scalability through which biologists can address a wide range of computer-intensive questions in biology and drug discovery.

  9. The affinity of the uranyl ion for nitrogen donor ligands

    Energy Technology Data Exchange (ETDEWEB)

    Jarvis, N.V. (Atomic Energy Corp. of South Africa Ltd., Pretoria (South Africa). Dept. of Process Technology); De Sousa, A.S.; Hancock, R.D. (Univ. of the Witwatersrand, Johannesburg (South Africa). Centre for Molecular Design)

    1992-01-01

    Established ligand design principles are used to predict the solution chemistry of UO[sub 2][sup 2+] with nitrogen donor ligands which do not contain carboxylate donors. pK[sub a]'s of the nitrogen donors are lowered by addition of hydroxylalkyl groups causing UO[sub 2][sup 2+] to have a greater affinity for these ligands than for hydroxide. Potentiometric studies using the ligands N,N,N',N',N''-pentakis(2-hydroxypropyl)-1,4,7-triazaheptane; N,N,N',N',N''-pentakis(2-hydroxyethyl)-1,4,7-triazaheptane; N,N,N',N'-tetrakis(2-hydroxypropyl)1,2-diaminoethane, N,N,N',N'-tetrakis(2-hydroxyethyl)-trans-1,2-diaminocyclohexane; 1,4,8,11-tetrakis(2-hydroxyethyl)-1,4,8,11-tetraazacyclotetradecane and N,N-bis(2-hydroxyethyl)glycine with UO[sub 2][sup 2+] showed that UO[sub 2][sup 2+] has a considerable aqueous solution chemistry with these ligands. (orig.).

  10. Selective extraction of trivalent actinides with hard-soft mixed donor ligands: role of intra-ligand synergism

    International Nuclear Information System (INIS)

    Ghanty, Tapan K.

    2016-01-01

    In recent years, considerable attention has been given to understand the coordination chemistry of trivalent lanthanide (Ln) and actinide (An) with various ligands because of its close link with the nuclear waste management processes. It is well known that lanthanide-actinide separation is a challenging and difficult task because of very similar chemical properties of these two series of ions, which are associated with similar ionic radii and coordination numbers. Recently, we have introduced a new concept, 'intra-ligand synergism', where hard donor atom, such as, oxygen preferentially binds to trivalent actinides (An(III)) as compared to the valence iso-electronic trivalent lanthanides (Ln(III)) in presence of another soft donor centre. In the present work, the conventional concept of selective complexation of actinides with soft donor ligands (either S or N donor) has been modified through exploiting this concept, and thereby the higher selectivity of 1,10-phenanthroline-2,9-dicarboxylamide (PDAM) based ligands, namely PDAM and its isobutyl and decyl derivatives towards Am(III) ion has been predicted theoretically through density functional calculations. Subsequently, several such amide derivatives have been synthesized to optimize the solubility of the ligands in organic phase. Finally, solvent extraction experiments have been carried out to validate the theoretical prediction on the selectivity of oxygen donor ligands towards Am(III) as compared to Eu(III), and a maximum separation factor of about 51 has been achieved experimentally using 2,9-bis(N-decylaminocarbonyl)-1,10-phenanthroline ligand. The separation factor is increased with the decrease in pH, which is very interesting since extraction of the Am 3+ ion is considered to be important under highly acidic conditions from the nuclear waste management point of view. (author)

  11. Conformational diversity of flexible ligand in metal-organic frameworks controlled by size-matching mixed ligands

    International Nuclear Information System (INIS)

    Hua, Xiu-Ni; Qin, Lan; Yan, Xiao-Zhi; Yu, Lei; Xie, Yi-Xin; Han, Lei

    2015-01-01

    Hydrothermal reactions of N-auxiliary flexible exo-bidentate ligand 1,3-bis(4-pyridyl)propane (bpp) and carboxylates ligands naphthalene-2,6-dicarboxylic acid (2,6-H_2ndc) or 4,4′-(hydroxymethylene)dibenzoic acid (H_2hmdb), in the presence of cadmium(II) salts have given rise to two novel metal-organic frameworks based on flexible ligands (FL-MOFs), namely, [Cd_2(2,6-ndc)_2(bpp)(DMF)]·2DMF (1) and [Cd_3(hmdb)_3(bpp)]·2DMF·2EtOH (2) (DMF=N,N-Dimethylformamide). Single-crystal X-ray diffraction analyses revealed that compound 1 exhibits a three-dimensional self-penetrating 6-connected framework based on dinuclear cluster second building unit. Compound 2 displays an infinite three-dimensional ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster and V-shaped organic linkers. The flexible bpp ligand displays different conformations in 1 and 2, which are successfully controlled by size-matching mixed ligands during the self-assembly process. - Graphical abstract: Compound 1 exhibits a 3D self-penetrating 6-connected framework based on dinuclear cluster, and 2 displays an infinite 3D ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster. The flexible 1,3-bis(4-pyridyl)propane ligand displays different conformations in 1 and 2, which successfully controlled by size-matching mixed ligands during the self-assembly process.

  12. Conformational diversity of flexible ligand in metal-organic frameworks controlled by size-matching mixed ligands

    Energy Technology Data Exchange (ETDEWEB)

    Hua, Xiu-Ni; Qin, Lan; Yan, Xiao-Zhi; Yu, Lei; Xie, Yi-Xin; Han, Lei, E-mail: hanlei@nbu.edu.cn

    2015-12-15

    Hydrothermal reactions of N-auxiliary flexible exo-bidentate ligand 1,3-bis(4-pyridyl)propane (bpp) and carboxylates ligands naphthalene-2,6-dicarboxylic acid (2,6-H{sub 2}ndc) or 4,4′-(hydroxymethylene)dibenzoic acid (H{sub 2}hmdb), in the presence of cadmium(II) salts have given rise to two novel metal-organic frameworks based on flexible ligands (FL-MOFs), namely, [Cd{sub 2}(2,6-ndc){sub 2}(bpp)(DMF)]·2DMF (1) and [Cd{sub 3}(hmdb){sub 3}(bpp)]·2DMF·2EtOH (2) (DMF=N,N-Dimethylformamide). Single-crystal X-ray diffraction analyses revealed that compound 1 exhibits a three-dimensional self-penetrating 6-connected framework based on dinuclear cluster second building unit. Compound 2 displays an infinite three-dimensional ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster and V-shaped organic linkers. The flexible bpp ligand displays different conformations in 1 and 2, which are successfully controlled by size-matching mixed ligands during the self-assembly process. - Graphical abstract: Compound 1 exhibits a 3D self-penetrating 6-connected framework based on dinuclear cluster, and 2 displays an infinite 3D ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster. The flexible 1,3-bis(4-pyridyl)propane ligand displays different conformations in 1 and 2, which successfully controlled by size-matching mixed ligands during the self-assembly process.

  13. Robotic environments

    NARCIS (Netherlands)

    Bier, H.H.

    2011-01-01

    Technological and conceptual advances in fields such as artificial intelligence, robotics, and material science have enabled robotic architectural environments to be implemented and tested in the last decade in virtual and physical prototypes. These prototypes are incorporating sensing-actuating

  14. Performative Environments

    DEFF Research Database (Denmark)

    Thomsen, Bo Stjerne

    2008-01-01

    The paper explores how performative architecture can act as a collective environment localizing urban flows and establishing public domains through the integration of pervasive computing and animation techniques. The NoRA project introduces the concept of ‘performative environments,' focusing on ...... of local interactions and network behaviour, building becomes social infrastructure and prompts an understanding of architectural structures as quasiobjects, which can retain both variation and recognisability in changing social constellations.......The paper explores how performative architecture can act as a collective environment localizing urban flows and establishing public domains through the integration of pervasive computing and animation techniques. The NoRA project introduces the concept of ‘performative environments,' focusing...

  15. Highly efficient bioinspired molecular Ru water oxidation catalysts with negatively charged backbone ligands.

    Science.gov (United States)

    Duan, Lele; Wang, Lei; Li, Fusheng; Li, Fei; Sun, Licheng

    2015-07-21

    The oxygen evolving complex (OEC) of the natural photosynthesis system II (PSII) oxidizes water to produce oxygen and reducing equivalents (protons and electrons). The oxygen released from PSII provides the oxygen source of our atmosphere; the reducing equivalents are used to reduce carbon dioxide to organic products, which support almost all organisms on the Earth planet. The first photosynthetic organisms able to split water were proposed to be cyanobacteria-like ones appearing ca. 2.5 billion years ago. Since then, nature has chosen a sustainable way by using solar energy to develop itself. Inspired by nature, human beings started to mimic the functions of the natural photosynthesis system and proposed the concept of artificial photosynthesis (AP) with the view to creating energy-sustainable societies and reducing the impact on the Earth environments. Water oxidation is a highly energy demanding reaction and essential to produce reducing equivalents for fuel production, and thereby effective water oxidation catalysts (WOCs) are required to catalyze water oxidation and reduce the energy loss. X-ray crystallographic studies on PSII have revealed that the OEC consists of a Mn4CaO5 cluster surrounded by oxygen rich ligands, such as oxyl, oxo, and carboxylate ligands. These negatively charged, oxygen rich ligands strongly stabilize the high valent states of the Mn cluster and play vital roles in effective water oxidation catalysis with low overpotential. This Account describes our endeavors to design effective Ru WOCs with low overpotential, large turnover number, and high turnover frequency by introducing negatively charged ligands, such as carboxylate. Negatively charged ligands stabilized the high valent states of Ru catalysts, as evidenced by the low oxidation potentials. Meanwhile, the oxygen production rates of our Ru catalysts were improved dramatically as well. Thanks to the strong electron donation ability of carboxylate containing ligands, a seven

  16. Designing multiple ligands - medicinal chemistry strategies and challenges.

    Science.gov (United States)

    Morphy, Richard; Rankovic, Zoran

    2009-01-01

    It has been widely recognised over the recent years that parallel modulation of multiple biological targets can be beneficial for treatment of diseases with complex etiologies such as cancer asthma, and psychiatric disease. In this article, current strategies for the generation of ligands with a specific multi-target profile (designed multiple ligands or DMLs) are described and a number of illustrative example are given. Designing multiple ligands is frequently a challenging endeavour for medicinal chemists, with the need to appropriately balance affinity for 2 or more targets whilst obtaining physicochemical and pharmacokinetic properties that are consistent with the administration of an oral drug. Given that the properties of DMLs are influenced to a large extent by the proteomic superfamily to which the targets belong and the lead generation strategy that is pursued, an early assessment of the feasibility of any given DML project is essential.

  17. Evaluation of macrocyclic hydroxyisophthalamide ligands as chelators for zirconium-89.

    Science.gov (United States)

    Bhatt, Nikunj B; Pandya, Darpan N; Xu, Jide; Tatum, David; Magda, Darren; Wadas, Thaddeus J

    2017-01-01

    The development of bifunctional chelators (BFCs) for zirconium-89 immuno-PET applications is an area of active research. Herein we report the synthesis and evaluation of octadentate hydroxyisophthalamide ligands (1 and 2) as zirconium-89 chelators. While both radiometal complexes could be prepared quantitatively and with excellent specific activity, preparation of 89Zr-1 required elevated temperature and an increased reaction time. 89Zr-1 was more stable than 89Zr-2 when challenged in vitro by excess DTPA or serum proteins and in vivo during acute biodistribution studies. Differences in radiometal complex stability arise from structural changes between the two ligand systems, and suggest further ligand optimization is necessary to enhance 89Zr chelation.

  18. Evaluation of macrocyclic hydroxyisophthalamide ligands as chelators for zirconium-89.

    Directory of Open Access Journals (Sweden)

    Nikunj B Bhatt

    Full Text Available The development of bifunctional chelators (BFCs for zirconium-89 immuno-PET applications is an area of active research. Herein we report the synthesis and evaluation of octadentate hydroxyisophthalamide ligands (1 and 2 as zirconium-89 chelators. While both radiometal complexes could be prepared quantitatively and with excellent specific activity, preparation of 89Zr-1 required elevated temperature and an increased reaction time. 89Zr-1 was more stable than 89Zr-2 when challenged in vitro by excess DTPA or serum proteins and in vivo during acute biodistribution studies. Differences in radiometal complex stability arise from structural changes between the two ligand systems, and suggest further ligand optimization is necessary to enhance 89Zr chelation.

  19. Ligand screening by saturation-transfer difference (STD) NMR spectroscopy.

    Energy Technology Data Exchange (ETDEWEB)

    Krishnan, V V

    2005-04-26

    NMR based methods to screen for high-affinity ligands have become an indispensable tool for designing rationalized drugs, as these offer a combination of good experimental design of the screening process and data interpretation methods, which together provide unprecedented information on the complex nature of protein-ligand interactions. These methods rely on measuring direct changes in the spectral parameters, that are often simpler than the complex experimental procedures used to study structure and dynamics of proteins. The goal of this review article is to provide the basic details of NMR based ligand-screening methods, with particular focus on the saturation transfer difference (STD) experiment. In addition, we provide an overview of other NMR experimental methods and a practical guide on how to go about designing and implementing them.

  20. Lanthanide and actinide complexation studies with tetradentate 'N' donor ligands

    International Nuclear Information System (INIS)

    Bhattacharyya, A.; Mohapatra, M.; Mohapatra, P.K.; Rawat, N.; Tomar, B.S.; Gadly, T.; Ghosh, S.K.; Manna, D.; Ghanty, T.K.

    2014-01-01

    Because of their similar charge and chemical behaviour separation of trivalent actinides and lanthanides is an important and challenging task in nuclear fuel cycle. Soft (S,N) donor ligands show selectivity towards the trivalent actinides over the lanthanides. Out of various 'N' donor ligands studied, bis(1,2,4)triazinyl bipyridine (BTBP) and bis(1,2,4)triazinyl phenanthroline (BTPhen) were found to be most promising. In order to understand the separation behaviour of these ligands, their complexation studies with these 'f' block elements are essential. In the present work, complexation studies of various lanthanide ions (La 3+ , Eu 3+ and Er 3+ ) was studied with ethyl derivatives of BTBP (C 2 BTBP) and BTBPhen (C 2 BTPhen) and pentyl derivative of BTBP (C 5 BTBP) in acetonitrile medium using UV-Vis spectrophotometry, fluorescence spectroscopy and solution calorimetry. Computational studies were also carried out to understand the experimental results

  1. Analytical developments for screening of lanthanides/ligands interactions

    International Nuclear Information System (INIS)

    Varenne, F.

    2012-01-01

    This work investigates the potential of hyphenated capillary electrophoresis and inductively coupled mass spectrometry to classify different ligands according to their europium binding affinity in a hydro-organic medium. On the one hand, this method enables to evaluate the affinity of phosphorus-containing ligands in less than two hours and using less than 15 ng of ligand. On the other hand, complexation constants could be determined. The results are in excellent agreement with the values obtained by spectrophotometric titrations.Moreover, a library of copolymers for solid/liquid extraction of europium is investigated. The extraction protocol enables to classify copolymers according to their europium affinity in a hydro-organic medium. This screening requires 60 mg of copolymers. For the most promising recognition properties and selectivity La 3+ /Eu 3+ /Lu 3+ are evaluated. (author)

  2. Xanthene and Xanthone Derivatives as G-Quadruplex Stabilizing Ligands

    Directory of Open Access Journals (Sweden)

    Alessandro Altieri

    2013-10-01

    Full Text Available Following previous studies on anthraquinone and acridine-based G-quadruplex ligands, here we present a study of similar aromatic cores, with the specific aim of increasing G-quadruplex binding and selectivity with respect to duplex DNA. Synthesized compounds include two and three-side chain xanthone and xanthene derivatives, as well as a dimeric “bridged” form. ESI and FRET measurements suggest that all the studied molecules are good G-quadruplex ligands, both at telomeres and on G-quadruplex forming sequences of oncogene promoters. The dimeric compound and the three-side chain xanthone derivative have been shown to represent the best compounds emerging from the different series of ligands presented here, having also high selectivity for G-quadruplex structures with respect to duplex DNA. Molecular modeling simulations are in broad agreement with the experimental data.

  3. Ligands Exchange Process on Gold Nanoparticles in Acetone Solution

    Science.gov (United States)

    Hu, C. L.; Mu, Y. Y.; Bian, Z. C.; Luo, Z. H.; Luo, K.; Huang, A. Z.

    2018-05-01

    The ligands exchange process on gold nanoparticles (GNPs) was proceeded by using hydrophobic group (PPh3) and hydrophilic group (THPO) in acetone solution. The FTIR and XPS results demonstrated that part of THPO was replaced by PPh3 which was dissolved in polar solution (acetone); the results were in accordance with the electrochemical analysis where the differential capacity decreased with increasing exchange time. After 12 h, the exchange process terminated and the final ratio of PPh3 and THPO was about 1.4: 1. This ratio remained unchanged although the PPh3 and THPO modified GNPs re-dispersed in the PPh3 acetone solution demonstrating the stable adsorption of both ligands after exchanging for 12 h. The TEM images showed that the gold nanoparticles were self-assembled from scattered to arranged morphology due to the existence of hydrophilic and hydrophobic ligands and led to Janus gold nanoparticles.

  4. A tandem regression-outlier analysis of a ligand cellular system for key structural modifications around ligand binding.

    Science.gov (United States)

    Lin, Ying-Ting

    2013-04-30

    A tandem technique of hard equipment is often used for the chemical analysis of a single cell to first isolate and then detect the wanted identities. The first part is the separation of wanted chemicals from the bulk of a cell; the second part is the actual detection of the important identities. To identify the key structural modifications around ligand binding, the present study aims to develop a counterpart of tandem technique for cheminformatics. A statistical regression and its outliers act as a computational technique for separation. A PPARγ (peroxisome proliferator-activated receptor gamma) agonist cellular system was subjected to such an investigation. Results show that this tandem regression-outlier analysis, or the prioritization of the context equations tagged with features of the outliers, is an effective regression technique of cheminformatics to detect key structural modifications, as well as their tendency of impact to ligand binding. The key structural modifications around ligand binding are effectively extracted or characterized out of cellular reactions. This is because molecular binding is the paramount factor in such ligand cellular system and key structural modifications around ligand binding are expected to create outliers. Therefore, such outliers can be captured by this tandem regression-outlier analysis.

  5. Systematic study of ligand structures of metal oxide EUV nanoparticle photoresists

    KAUST Repository

    Jiang, Jing

    2015-03-19

    Ligand stabilized metal oxide nanoparticle resists are promising candidates for EUV lithography due to their high sensitivity for high-resolution patterning and high etching resistance. As ligand exchange is responsible for the patterning mechanism, we systematically studied the influence of ligand structures of metal oxide EUV nanoparticles on their sensitivity and dissolution behavior. ZrO2 nanoparticles were protected with various aromatic ligands with electron withdrawing and electron donating groups. These nanoparticles have lower sensitivity compared to those with aliphatic ligands suggesting the structures of these ligands is more important than their pka on resist sensitivity. The influence of ligand structure was further studied by comparing the nanoparticles’ solubility for a single type ligand to mixtures of ligands. The mixture of nanoparticles showed improved pattern quality. © (2015) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

  6. Radioactive contaminants in the subsurface: the influence of complexing ligands on trace metal speciation

    International Nuclear Information System (INIS)

    Hummel, W. . Author

    2006-01-01

    Equilibrium thermodynamics is one of the pillars which support safety analyzes of repositories for radioactive waste. The research summarized in this review deals with approaches to resolve the problems related to thermodynamic equilibrium constants and solubility of solid phases in the field of radioactive waste management. The results have been obtained at the Paul Scherrer Institut between 1995 and 2005 and comprise the scientific basis of the author's habilitation thesis in the field of nuclear environmental chemistry. The topics are grouped according to three different levels of problem solving strategies: critical and comprehensive reviews of the available literature, which are necessary in order to establish a reliable chemical thermodynamic database that fulfils the requirements for rigorous modeling of the behavior of the actinides and fission products in the environment. In many case studies involving inorganic and simple organic ligands a serious lack of reliable thermodynamic data is encountered. There, a new modeling approach to estimate the effects of these missing data was applied. This so called 'backdoor approach' begins with the question, 'What total concentration of a ligand is necessary to significantly influence the speciation, and hence the solubility, of a given trace metal?' In the field of natural organics, mainly humic and fulvic acids, we face an ill-defined problem concerning the molecular structure of the ligands. There, a pragmatic approach for performance assessment purposes was applied, the 'conservative roof' approach, which does not aim to accurately model all experimental data, but allows estimates of maximum effects on metal complexation by humic substances to be calculated. (author)

  7. Synthesis and spectroscopic behavior of highly luminescent trinuclear europium complexes with tris-β-diketone ligand

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Dunjia, E-mail: dunjiawang@163.com; Pi, Yan; Liu, Hua; Wei, Xianhong; Hu, Yanjun; Zheng, Jing

    2014-11-15

    Highlights: • Synthesis of the tris-β-diketone ligand and its trinuclear europium complexes. • Photoluminescence behavior of trinuclear europium complexes. • Analysis of the Judd–Ofelt intensity parameters (Ω{sub t}), lifetime (τ) and quantum yield (η). - Abstract: A new tris-β-diketone ligand, 2-[4,6-bis-(1-benzoyl-2-oxo-2-phenyl-ethyl)-[1,3,5]triazin-2-yl] -1,3-diphenyl-propane-1,3-dione (H{sub 3}L), and its trinuclear europium complexes, Eu{sub 3}(DBM){sub 6}L (C1), Eu{sub 3}(DBM){sub 6}(Bipy){sub 3}L (C2) and Eu{sub 3}(DBM){sub 6}(Phen){sub 3}L (C3) were synthesized and their spectroscopic behaviors were studied by FT-IR, {sup 1}H NMR, UV–vis and photoluminescence spectroscopic techniques. These europium complexes exhibited the characteristic emission bands that arise from the {sup 5}D{sub 0} → {sup 7}F{sub J} (J = 0–4) transitions of the europium ion in solid state. The Ω{sub 2} and Ω{sub 4} intensity parameters, lifetime (τ) and luminescence quantum yield (η) were calculated according to the emission spectra and luminescence decay curves in solid state. The results indicated that these trinuclear europium complexes displayed a longer lifetime (τ) and higher luminescence quantum efficiency (η), especially complexes C2 (τ = 0.820 ms, η = 46.5%) and C3 (τ = 0.804 ms, η = 47.4%), which due to the effect of two additional europium ion lumophors and the introduction of the third ligands, Bipy or Phen in trinuclear complexes. Their Ω{sub 2} values demonstrated that the europium ion in these complexes is in a highly polarizable chemical environment.

  8. Spectroscopic study of cadmium (II) complexes with heterocyclic dithiocarbamate ligands

    International Nuclear Information System (INIS)

    Garcia-Fontan, S.; Rodriguez-Seoane, P.; Casas, J.S.; Sordo, J.; Jones, M.M.

    1993-01-01

    Cadmium(II) dithiocarbamates [Cd(dtc) 2 ] (dtc=4-carboxamidopiperidine-1-carbodithioate, morpholine-1-carbodithioate or 4-(2-hydroxyethyl)piperazine-1-carbodithioate) and [Cd(dtc) 2 ].H 2 O (dtc=4-hydroxypiperidine-1-carbodithioate} have been prepared and characterized by thermal analysis and IR and NMR ( 13 C, 113 Cd) spectrometry. Two of these ligands have previously been shown capable of removing cadmium from its aged in vivo storage sites. The use of solid state 13 C NMR measurements to establish the coordination mode of the dithiocarbomate ligands is also examined and the difficulties which arise are discussed. (orig.)

  9. Designer ligands: The search for metal ion selectivity

    Directory of Open Access Journals (Sweden)

    Perry T. Kaye

    2011-03-01

    Full Text Available The paper reviews research conducted at Rhodes University towards the development of metal-selective ligands. The research has focused on the rational design, synthesis and evaluation of novel ligands for use in the formation of copper complexes as biomimetic models of the metalloenzyme, tyrosinase, and for the selective extraction of silver, nickel and platinum group metal ions in the presence of contaminating metal ions. Attention has also been given to the development of efficient, metal-selective molecular imprinted polymers.

  10. Introducing various ligands into superhalogen anions reduces their electronic stabilities

    Science.gov (United States)

    Smuczyńska, Sylwia; Skurski, Piotr

    2008-02-01

    The vertical electron detachment energies (VDE) of six NaX2- anions (where X = F, Cl, Br) were calculated at the OVGF level with the 6-311++G(3df) basis sets. In all the cases studied the VDE exceeds the electron affinity of chlorine atom and thus those species were classified as superhalogen anions. The largest vertical binding energy was found for the NaF2- system (6.644 eV). The strong VDE dependence on the ligand type, ligand-central atom distance, and the character of the highest occupied molecular orbital (HOMO) was observed and discussed.

  11. Long ligands reinforce biological adhesion under shear flow

    Science.gov (United States)

    Belyaev, Aleksey V.

    2018-04-01

    In this work, computer modeling has been used to show that longer ligands allow biological cells (e.g., blood platelets) to withstand stronger flows after their adhesion to solid walls. A mechanistic model of polymer-mediated ligand-receptor adhesion between a microparticle (cell) and a flat wall has been developed. The theoretical threshold between adherent and non-adherent regimes has been derived analytically and confirmed by simulations. These results lead to a deeper understanding of numerous biophysical processes, e.g., arterial thrombosis, and to the design of new biomimetic colloid-polymer systems.

  12. Force loading explains spatial sensing of ligands by cells

    Science.gov (United States)

    Oria, Roger; Wiegand, Tina; Escribano, Jorge; Elosegui-Artola, Alberto; Uriarte, Juan Jose; Moreno-Pulido, Cristian; Platzman, Ilia; Delcanale, Pietro; Albertazzi, Lorenzo; Navajas, Daniel; Trepat, Xavier; García-Aznar, José Manuel; Cavalcanti-Adam, Elisabetta Ada; Roca-Cusachs, Pere

    2017-12-01

    Cells can sense the density and distribution of extracellular matrix (ECM) molecules by means of individual integrin proteins and larger, integrin-containing adhesion complexes within the cell membrane. This spatial sensing drives cellular activity in a variety of normal and pathological contexts. Previous studies of cells on rigid glass surfaces have shown that spatial sensing of ECM ligands takes place at the nanometre scale, with integrin clustering and subsequent formation of focal adhesions impaired when single integrin-ligand bonds are separated by more than a few tens of nanometres. It has thus been suggested that a crosslinking ‘adaptor’ protein of this size might connect integrins to the actin cytoskeleton, acting as a molecular ruler that senses ligand spacing directly. Here, we develop gels whose rigidity and nanometre-scale distribution of ECM ligands can be controlled and altered. We find that increasing the spacing between ligands promotes the growth of focal adhesions on low-rigidity substrates, but leads to adhesion collapse on more-rigid substrates. Furthermore, disordering the ligand distribution drastically increases adhesion growth, but reduces the rigidity threshold for adhesion collapse. The growth and collapse of focal adhesions are mirrored by, respectively, the nuclear or cytosolic localization of the transcriptional regulator protein YAP. We explain these findings not through direct sensing of ligand spacing, but by using an expanded computational molecular-clutch model, in which individual integrin-ECM bonds—the molecular clutches—respond to force loading by recruiting extra integrins, up to a maximum value. This generates more clutches, redistributing the overall force among them, and reducing the force loading per clutch. At high rigidity and high ligand spacing, maximum recruitment is reached, preventing further force redistribution and leading to adhesion collapse. Measurements of cellular traction forces and actin flow speeds

  13. How does the addition of steric hindrance to a typical N-heterocyclic carbene ligand affect catalytic activity in olefin metathesis?

    KAUST Repository

    Poater, Albert; Falivene, Laura; Urbina-Blanco, Cé sar A.; Manzini, Simone; Nolan, Steven P.; Cavallo, Luigi

    2013-01-01

    Density functional theory (DFT) calculations were used to predict and rationalize the effect of the modification of the structure of the prototype 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) N-heterocyclic carbene (NHC) ligand. The modification consists in the substitution of the methyl groups of ortho isopropyl substituent with phenyl groups, and here we plan to describe how such significant changes affect the metal environment and therefore the related catalytic behaviour. Bearing in mind that there is a significant structural difference between both ligands in different olefin metathesis reactions, here by means of DFT we characterize where the NHC ligand plays a more active role and where it is a simple spectator, or at least its modification does not significantly change its catalytic role/performance. © 2013 The Royal Society of Chemistry.

  14. Binding equilibrium and kinetics of membrane-anchored receptors and ligands in cell adhesion: Insights from computational model systems and theory

    Science.gov (United States)

    Weikl, Thomas R.; Hu, Jinglei; Xu, Guang-Kui; Lipowsky, Reinhard

    2016-01-01

    ABSTRACT The adhesion of cell membranes is mediated by the binding of membrane-anchored receptor and ligand proteins. In this article, we review recent results from simulations and theory that lead to novel insights on how the binding equilibrium and kinetics of these proteins is affected by the membranes and by the membrane anchoring and molecular properties of the proteins. Simulations and theory both indicate that the binding equilibrium constant K2D and the on- and off-rate constants of anchored receptors and ligands in their 2-dimensional (2D) membrane environment strongly depend on the membrane roughness from thermally excited shape fluctuations on nanoscales. Recent theory corroborated by simulations provides a general relation between K2D and the binding constant K3D of soluble variants of the receptors and ligands that lack the membrane anchors and are free to diffuse in 3 dimensions (3D). PMID:27294442

  15. Synthetic environments

    Science.gov (United States)

    Lukes, George E.; Cain, Joel M.

    1996-02-01

    The Advanced Distributed Simulation (ADS) Synthetic Environments Program seeks to create robust virtual worlds from operational terrain and environmental data sources of sufficient fidelity and currency to interact with the real world. While some applications can be met by direct exploitation of standard digital terrain data, more demanding applications -- particularly those support operations 'close to the ground' -- are well-served by emerging capabilities for 'value-adding' by the user working with controlled imagery. For users to rigorously refine and exploit controlled imagery within functionally different workstations they must have a shared framework to allow interoperability within and between these environments in terms of passing image and object coordinates and other information using a variety of validated sensor models. The Synthetic Environments Program is now being expanded to address rapid construction of virtual worlds with research initiatives in digital mapping, softcopy workstations, and cartographic image understanding. The Synthetic Environments Program is also participating in a joint initiative for a sensor model applications programer's interface (API) to ensure that a common controlled imagery exploitation framework is available to all researchers, developers and users. This presentation provides an introduction to ADS and the associated requirements for synthetic environments to support synthetic theaters of war. It provides a technical rationale for exploring applications of image understanding technology to automated cartography in support of ADS and related programs benefitting from automated analysis of mapping, earth resources and reconnaissance imagery. And it provides an overview and status of the joint initiative for a sensor model API.

  16. Enacting Environments

    DEFF Research Database (Denmark)

    Lippert, Ingmar

    2013-01-01

    Enacting Environments is an ethnography of the midst of the encounter between corporations, sustainable development and climate change. At this intersection 'environmental management' and 'carbon accounting' are put into practice. Purportedly, these practices green capitalism. Drawing on fieldwork...... of day-to-day practices of corporate environmental accountants and managers, Ingmar Lippert reconstructs their work as achieving to produce a reality of environment that is simultaneously stable and flexible enough for a particular corporate project: to stage the company, and in consequence capitalism......, as in control over its relations to an antecedent environment. Not confined to mere texts or meetings between shiny stakeholders co-governing the corporation – among them some of the world's biggest auditing firms, an environmental non-governmental organisation (NGO) and standards – control is found...

  17. Glucagon-like peptide-1 receptor ligand interactions: structural cross talk between ligands and the extracellular domain.

    Directory of Open Access Journals (Sweden)

    Graham M West

    Full Text Available Activation of the glucagon-like peptide-1 receptor (GLP-1R in pancreatic β-cells potentiates insulin production and is a current therapeutic target for the treatment of type 2 diabetes mellitus (T2DM. Like other class B G protein-coupled receptors (GPCRs, the GLP-1R contains an N-terminal extracellular ligand binding domain. N-terminal truncations on the peptide agonist generate antagonists capable of binding to the extracellular domain, but not capable of activating full length receptor. The main objective of this study was to use Hydrogen/deuterium exchange (HDX to identify how the amide hydrogen bonding network of peptide ligands and the extracellular domain of GLP-1R (nGLP-1R were altered by binding interactions and to then use this platform to validate direct binding events for putative GLP-1R small molecule ligands. The HDX studies presented here for two glucagon-like peptide-1 receptor (GLP-1R peptide ligands indicates that the antagonist exendin-4[9-39] is significantly destabilized in the presence of nonionic detergents as compared to the agonist exendin-4. Furthermore, HDX can detect stabilization of exendin-4 and exendin-4[9-39] hydrogen bonding networks at the N-terminal helix [Val19 to Lys27] upon binding to the N-terminal extracellular domain of GLP-1R (nGLP-1R. In addition we show hydrogen bonding network stabilization on nGLP-1R in response to ligand binding, and validate direct binding events with the extracellular domain of the receptor for putative GLP-1R small molecule ligands.

  18. Heuristic Environments

    Directory of Open Access Journals (Sweden)

    Ines Giunta

    2011-10-01

    Full Text Available The purpose of this research is the identification of a paradigm which fixes the basic concepts and the type of logical relationships between them, whereby direct, govern and evaluate choises on new technologies. The contribution is based on the assumption that the complexity of knowledge is correlated with the complexity of the learning environment. From the existence of this correlation will descend a series of consequences that contribute to the definition of a theoretical construct in which the logical categories of learning become the guiding criteria on which to design learning environments and, consequently, also the indicators on by which to evaluate its effectiveness.

  19. Bio-Inspired Nitrile Hydration by Peptidic Ligands Based on L-Cysteine, L-Methionine or L-Penicillamine and Pyridine-2,6-dicarboxylic Acid

    Directory of Open Access Journals (Sweden)

    Cillian Byrne

    2014-12-01

    Full Text Available Nitrile hydratase (NHase, EC 4.2.1.84 is a metalloenzyme which catalyses the conversion of nitriles to amides. The high efficiency and broad substrate range of NHase have led to the successful application of this enzyme as a biocatalyst in the industrial syntheses of acrylamide and nicotinamide and in the bioremediation of nitrile waste. Crystal structures of both cobalt(III- and iron(III-dependent NHases reveal an unusual metal binding motif made up from six sequential amino acids and comprising two amide nitrogens from the peptide backbone and three cysteine-derived sulfur ligands, each at a different oxidation state (thiolate, sulfenate and sulfinate. Based on the active site geometry revealed by these crystal structures, we have designed a series of small-molecule ligands which integrate essential features of the NHase metal binding motif into a readily accessible peptide environment. We report the synthesis of ligands based on a pyridine-2,6-dicarboxylic acid scaffold and L-cysteine, L-S-methylcysteine, L-methionine or L-penicillamine. These ligands have been combined with cobalt(III and iron(III and tested as catalysts for biomimetic nitrile hydration. The highest levels of activity are observed with the L-penicillamine ligand which, in combination with cobalt(III, converts acetonitrile to acetamide at 1.25 turnovers and benzonitrile to benzamide at 1.20 turnovers.

  20. Challenges for the development of a biotic ligand model predicting copper toxicity in estuaries and seas.

    Science.gov (United States)

    de Polo, Anna; Scrimshaw, Mark D

    2012-02-01

    An effort is ongoing to develop a biotic ligand model (BLM) that predicts copper (Cu) toxicity in estuarine and marine environments. At present, the BLM accounts for the effects of water chemistry on Cu speciation, but it does not consider the influence of water chemistry on the physiology of the organisms. We discuss how chemistry affects Cu toxicity not only by controlling its speciation, but also by affecting the osmoregulatory physiology of the organism, which varies according to salinity. In an attempt to understand the mechanisms of Cu toxicity and predict its impacts, we explore the hypothesis that the common factor linking the main toxic effects of Cu is the enzyme carbonic anhydrase (CA), because it is a Cu target with multiple functions and salinity-dependent expression and activity. According to this hypothesis, the site of action of Cu in marine fish may be not only the gill, but also the intestine, because in this tissue CA plays an important role in ion transport and water adsorption. Therefore, the BLM of Cu toxicity to marine fish should also consider the intestine as a biotic ligand. Finally, we underline the need to incorporate the osmotic gradient into the BLM calculations to account for the influence of physiology on Cu toxicity. Copyright © 2011 SETAC.

  1. African Environment

    African Journals Online (AJOL)

    Environmental Studies and Regional Planning Bulletin African Environment is published in French and English, and for some issues, in Arabic. (only the issue below has been received by AJOL). Vol 10, No 3 (1999). DOWNLOAD FULL TEXT Open Access DOWNLOAD FULL TEXT Subscription or Fee Access. Table of ...

  2. Architecture & Environment

    Science.gov (United States)

    Erickson, Mary; Delahunt, Michael

    2010-01-01

    Most art teachers would agree that architecture is an important form of visual art, but they do not always include it in their curriculums. In this article, the authors share core ideas from "Architecture and Environment," a teaching resource that they developed out of a long-term interest in teaching architecture and their fascination with the…

  3. A Guided Inquiry Activity for Teaching Ligand Field Theory

    Science.gov (United States)

    Johnson, Brian J.; Graham, Kate J.

    2015-01-01

    This paper will describe a guided inquiry activity for teaching ligand field theory. Previous research suggests the guided inquiry approach is highly effective for student learning. This activity familiarizes students with the key concepts of molecular orbital theory applied to coordination complexes. Students will learn to identify factors that…

  4. Oxahelicene NHC ligands in the asymmetric synthesis of nonracemic helicenes

    Czech Academy of Sciences Publication Activity Database

    Gay Sánchez, Isabel; Šámal, Michal; Nejedlý, Jindřich; Karras, Manfred; Klívar, Jiří; Rybáček, Jiří; Buděšínský, Miloš; Bednárová, Lucie; Seidlerová, Beata; Stará, Irena G.; Starý, Ivo

    2017-01-01

    Roč. 53, č. 31 (2017), s. 4370-4373 ISSN 1359-7345 R&D Projects: GA ČR(CZ) GA14-29667S Institutional support: RVO:61388963 Keywords : helicene-based NHC ligands * enantioselective [2+2+2] cycloisomerisation Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 6.319, year: 2016

  5. Molecular dynamics simulations suggest ligand's binding to nicotinamidase/pyrazinamidase.

    Science.gov (United States)

    Zhang, Ji-Long; Zheng, Qing-Chuan; Li, Zheng-Qiang; Zhang, Hong-Xing

    2012-01-01

    The research on the binding process of ligand to pyrazinamidase (PncA) is crucial for elucidating the inherent relationship between resistance of Mycobacterium tuberculosis and PncA's activity. In the present study, molecular dynamics (MD) simulation methods were performed to investigate the unbinding process of nicotinamide (NAM) from two PncA enzymes, which is the reverse of the corresponding binding process. The calculated potential of mean force (PMF) based on the steered molecular dynamics (SMD) simulations sheds light on an optimal binding/unbinding pathway of the ligand. The comparative analyses between two PncAs clearly exhibit the consistency of the binding/unbinding pathway in the two enzymes, implying the universality of the pathway in all kinds of PncAs. Several important residues dominating the pathway were also determined by the calculation of interaction energies. The structural change of the proteins induced by NAM's unbinding or binding shows the great extent interior motion in some homologous region adjacent to the active sites of the two PncAs. The structure comparison substantiates that this region should be very important for the ligand's binding in all PncAs. Additionally, MD simulations also show that the coordination position of the ligand is displaced by one water molecule in the unliganded enzymes. These results could provide the more penetrating understanding of drug resistance of M. tuberculosis and be helpful for the development of new antituberculosis drugs.

  6. Molecular dynamics simulations suggest ligand's binding to nicotinamidase/pyrazinamidase.

    Directory of Open Access Journals (Sweden)

    Ji-Long Zhang

    Full Text Available The research on the binding process of ligand to pyrazinamidase (PncA is crucial for elucidating the inherent relationship between resistance of Mycobacterium tuberculosis and PncA's activity. In the present study, molecular dynamics (MD simulation methods were performed to investigate the unbinding process of nicotinamide (NAM from two PncA enzymes, which is the reverse of the corresponding binding process. The calculated potential of mean force (PMF based on the steered molecular dynamics (SMD simulations sheds light on an optimal binding/unbinding pathway of the ligand. The comparative analyses between two PncAs clearly exhibit the consistency of the binding/unbinding pathway in the two enzymes, implying the universality of the pathway in all kinds of PncAs. Several important residues dominating the pathway were also determined by the calculation of interaction energies. The structural change of the proteins induced by NAM's unbinding or binding shows the great extent interior motion in some homologous region adjacent to the active sites of the two PncAs. The structure comparison substantiates that this region should be very important for the ligand's binding in all PncAs. Additionally, MD simulations also show that the coordination position of the ligand is displaced by one water molecule in the unliganded enzymes. These results could provide the more penetrating understanding of drug resistance of M. tuberculosis and be helpful for the development of new antituberculosis drugs.

  7. Chelating ligands: enhancers of quality and purity of biogas ...

    African Journals Online (AJOL)

    The quality of biogas depends largely on the percentage of methane and hydrogen sulphide gas present. High concentration of hydrogen sulphide results in low quality biogas. This work employed the use of chelating ligands in scrubbing hydrogen sulphide gas while improving the yield of methane gas. Experimental ...

  8. GluR2 ligand-binding core complexes

    DEFF Research Database (Denmark)

    Kasper, C; Lunn, M-L; Liljefors, T

    2002-01-01

    X-ray structures of the GluR2 ligand-binding core in complex with (S)-Des-Me-AMPA and in the presence and absence of zinc ions have been determined. (S)-Des-Me-AMPA, which is devoid of a substituent in the 5-position of the isoxazolol ring, only has limited interactions with the partly hydrophobic...

  9. Synthesis of symmetrical and non-symmetrical bivalent neurotransmitter ligands

    DEFF Research Database (Denmark)

    Stuhr-Hansen, Nicolai; Andersen, Jacob; Thygesen, Mikkel Boas

    2016-01-01

    A novel procedure for synthesis of bivalent neurotransmitter ligands was developed by reacting O-benzyl protected N-nosylated dopamine and serotonin with alkyl- or PEG-linked diols under Fukuyama-Mitsunobu conditions in the presence of DIAD/PPh3 generating three different bivalent neurotransmitte...

  10. Lanthanide(III) Complexes with Tridentate Schiff Base Ligand ...

    African Journals Online (AJOL)

    Lanthanide complexes, hydrazino, antioxidant activity, X-ray structure. 1. Introduction ... measured using a Johnson Matthey scientific magnetic suscepti- bility balance. 2.1. .... of the ligand and that the nitrogen atom supporting this proton is not involved in the ... 4f-electrons are not involved in the coordination. These facts.

  11. The thermodynamic principles of ligand binding in chromatography and biology

    DEFF Research Database (Denmark)

    Mollerup, Jørgen

    2007-01-01

    the general thermodynamic principles of ligand binding. Models of the multi-component adsorption in ion-exchange and hydrophobic chromatography, HIC and RPLC, are developed. The parameters in the models have a well-defined physical significance. The models are compared to the Langmuir model...

  12. Optimal Overlay of Ligands with Flexible Bonds Using Differential Evolution

    DEFF Research Database (Denmark)

    Kristensen, Thomas Greve; Pedersen, Christian Storm

    2009-01-01

    might improve the quality of the search by taking all of these into account. This can be done by generating a meta-structure which summarizes the active ligands and use this meta-structure for querying the database. In this paper we propose a method for making such a meta-structure by making a multiple...

  13. Ligand-mediated adhesive mechanics of two static, deformed spheres.

    Science.gov (United States)

    Sircar, Sarthok; Nguyen, Giang; Kotousov, Andrei; Roberts, Anthony J

    2016-10-01

    A self-consistent model is developed to investigate attachment/detachment kinetics of two static, deformable microspheres with irregular surface and coated with flexible binding ligands. The model highlights how the microscale binding kinetics of these ligands as well as the attractive/repulsive potential of the charged surface affects the macroscale static deformed configuration of the spheres. It is shown that in the limit of smooth, neutrally charged surface (i.e., the dimensionless inverse Debye length, [Formula: see text]), interacting via elastic binders (i.e., the dimensionless stiffness coefficient, [Formula: see text]) the adhesion mechanics approaches the regime of application of the JKR theory, and in this particular limit, the contact radius, R c , scales with the particle radius, R, according to the scaling law, [Formula: see text]. We show that static, deformed, highly charged, ligand-coated surface of micro-spheres exhibit strong adhesion. Normal stress distribution within the contact area adjusts with the binder stiffness coefficient, from a maximum at the center to a maximum at the periphery of the region. Although reported in some in vitro experiments involving particle adhesion, until now a physical interpretation for this variation of the stress distribution for deformable, charged, ligand-coated microspheres is missing. Surface roughness results in a diminished adhesion with a distinct reduction in the pull-off force, larger separation gap, weaker normal stress and limited area of adhesion. These results are in agreement with the published experimental findings.

  14. Synergistic Effects of PPARγ Ligands and Retinoids in Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Masahito Shimizu

    2008-01-01

    Full Text Available Peroxisome proliferator-activated receptors (PPARs are members of the nuclear receptor superfamily. The activation of PPARs by their specific ligands is regarded as one of the promising strategies to inhibit cancer cell growth. However, recent clinical trials targeting several common cancers showed no beneficial effect when PPAR ligands are used as a monotherapy. Retinoid X receptors (RXRs, which play a critical role in normal cell proliferation as a master regulator for nuclear receptors, preferentially form heterodimers with PPARs. A malfunction of RXRα due to phosphorylation by the Ras/MAPK signaling pathway is associated with the development of certain types of human malignancies. The activation of PPARγ/RXR heterodimer by their respective ligands synergistically inhibits cell growth, while inducing apoptosis in human colon cancer cells when the phosphorylation of RXRα was inhibited. We herein review the synergistic antitumor effects produced by the combination of the PPAR, especially PPARγ, ligands plus other agents, especially retinoids, in a variety of human cancers. We also focus on the phosphorylation of RXRα because the inhibition of RXRα phosphorylation and the restoration of its physiological function may activate PPAR/RXR heterodimer and, therefore, be a potentially effective and critical strategy for the inhibition of cancer cell growth.

  15. (II) complexes containing isocyanide and labile nitrile ligands

    African Journals Online (AJOL)

    A new ruthenium(II) complex containing both acetonitrile and propionitrile moieties as coordinating ligands has been prepared. The treatment of the polymer [{RuCl2(COD)}x], (COD = cycloocta-1,5-diene) (1) with a mixture of acetonitrile and propionitrile under reflux produced a new precursor ...

  16. Water-soluble diphosphadiazacyclooctanes as ligands for aqueous organometallic catalysis

    KAUST Repository

    Boulanger, Jérôme

    2012-12-01

    Two new water-soluble diphosphacyclooctanes been synthesized and characterized by NMR and surface tension measurements. Both phosphanes proved to coordinate rhodium in a very selective way as well-defined bidentates were obtained. When used in Rh-catalyzed hydroformylation of terminal alkenes, both ligands positively impacted the reaction chemoselectivity. © 2012 Elsevier B.V.

  17. Biosensors engineered from conditionally stable ligand-binding domains

    Science.gov (United States)

    Church, George M.; Feng, Justin; Mandell, Daniel J.; Baker, David; Fields, Stanley; Jester, Benjamin Ward; Tinberg, Christine Elaine

    2017-09-19

    Disclosed is a biosensor engineered to conditionally respond to the presence of specific small molecules, the biosensors including conditionally stable ligand-binding domains (LBDs) which respond to the presence of specific small molecules, wherein readout of binding is provided by reporter genes or transcription factors (TFs) fused to the LBDs.

  18. The Ligand Substitution Reactions of Hydrophobic Vitamin B ...

    African Journals Online (AJOL)

    NJD

    Vitamin B. 12. Derivatives. Reaction of Cobyric Acid. Heptapropyl Ester with Heterocyclic N-donor Ligands. Mohamed S.A. .... RESEARCH ARTICLE. M.S.A. Hamza ..... neutralized with NaHCO3 and treated with excess KCN to give. DCCbs-Pr.

  19. Fluorescent ligands for studying neuropeptide receptors by confocal microscopy

    Directory of Open Access Journals (Sweden)

    A. Beaudet

    1998-11-01

    Full Text Available This paper reviews the use of confocal microscopy as it pertains to the identification of G-protein coupled receptors and the study of their dynamic properties in cell cultures and in mammalian brain following their tagging with specific fluorescent ligands. Principles that should guide the choice of suitable ligands and fluorophores are discussed. Examples are provided from the work carried out in the authors' laboratory using custom synthetized fluoresceinylated or BODIPY-tagged bioactive peptides. The results show that confocal microscopic detection of specifically bound fluorescent ligands permits high resolution appraisal of neuropeptide receptor distribution both in cell culture and in brain sections. Within the framework of time course experiments, it also allows for a dynamic assessment of the internalization and subsequent intracellular trafficking of bound fluorescent molecules. Thus, it was found that neurotensin, somatostatin and mu- and delta-selective opioid peptides are internalized in a receptor-dependent fashion and according to receptor-specific patterns into their target cells. In the case of neurotensin, this internalization process was found to be clathrin-mediated, to proceed through classical endosomal pathways and, in neurons, to result in a mobilization of newly formed endosomes from neural processes to nerve cell bodies and from the periphery of cell bodies towards the perinuclear zone. These mechanisms are likely to play an important role for ligand inactivation, receptor regulation and perhaps also transmembrane signaling.

  20. Tissue distribution of the death ligand TRAIL and its receptors

    NARCIS (Netherlands)

    Spierings, DC; de Vries, EG; Vellenga, E; van den Heuvel, FA; Koornstra, JJ; Wesseling, J; Hollema, H; de Jong, S

    Recombinant human (rh) TNF-related apoptosis-inducing ligand (TRAIL) harbors potential as an anticancer agent. RhTRAIL induces apoptosis via the TRAIL receptors TRAIL-R1 and TRAIL-R2 in tumors and is non-toxic to nonhuman primates. Because limited data are available about TRAIL receptor

  1. Synthesis and evaluation of potential ligands for nuclear waste processing

    NARCIS (Netherlands)

    Iqbal, M.

    2012-01-01

    The research presented in this thesis deals with the synthesis and evaluation of new potential ligands for the complexation of actinide and lanthanide ions either for their extraction from bulk radioactive waste or their stripping from an extracted organic phase for final processing of the waste. In

  2. Development and Application of Ligand-Exchange Reaction Method ...

    African Journals Online (AJOL)

    Purpose: This paper presents an improved kinetic-spectrophotometric procedure for determining clonazepam (CZP) in pharmaceutical formulations and human serum. Methods: The method is based on ligand-exchange reaction. The reaction was followed spectrophotometrically by measuring the rate of change of ...

  3. Amidinate Ligands in Zinc coordination sphere: Synthesis and ...

    Indian Academy of Sciences (India)

    Amidinate Ligands in Zinc coordination sphere: Synthesis and structural diversity. SRINIVAS ANGA, INDRANI BANERJEE and TARUN K PANDA. ∗. Department of Chemistry, Indian Institute of Technology Hyderabad, Kandi 502 285,. Sangareddy, Telangana, India e-mail: tpanda@iith.ac.in. MS received 25 February 2016; ...

  4. synthesis and spectra characterization of mixed- ligand complexes

    African Journals Online (AJOL)

    BARTH EKWUEME

    The Schiff base ligand, N-Propylidene-2-methylpyridylamine was obtained from the condensation of 2- aminomethypyridine and propanal.Also, its complexes with Cu(II),Ni(II),Zn(II),Co(II) .... determined with Thomas–Hoover capillary melting apparatus. RESULTS AND DISCUSSION. N-propylidene-2-methylpyridylamine ...

  5. Redox Potentials of Ligands and Complexes – a DFT Approach

    African Journals Online (AJOL)

    NICO

    A review of the limited literature concerned with theoretical ways to predict experimentally measured redox potentials of ligands and ... electrode surface, over-potentials and high solvent resistance, ... A correlation coefficient of 0.969 in the linear relation with ... of E0' were performed in two steps, i.e. calculation of the free.

  6. Selective Electrocatalytic Activity of Ligand Stabilized Copper Oxide Nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Kauffman, Douglas R; Ohodnicki, Paul R; Kail, Brian W; Matranga, Christopher

    2011-01-01

    Ligand stabilization can influence the surface chemistry of Cu oxide nanoparticles (NPs) and provide unique product distributions for electrocatalytic methanol (MeOH) oxidation and CO{sub 2} reduction reactions. Oleic acid (OA) stabilized Cu{sub 2}O and CuO NPs promote the MeOH oxidation reaction with 88% and 99.97% selective HCOH formation, respectively. Alternatively, CO{sub 2} is the only reaction product detected for bulk Cu oxides and Cu oxide NPs with no ligands or weakly interacting ligands. We also demonstrate that OA stabilized Cu oxide NPs can reduce CO{sub 2} into CO with a {approx}1.7-fold increase in CO/H{sub 2} production ratios compared to bulk Cu oxides. The OA stabilized Cu oxide NPs also show 7.6 and 9.1-fold increases in CO/H{sub 2} production ratios compared to weakly stabilized and non-stabilized Cu oxide NPs, respectively. Our data illustrates that the presence and type of surface ligand can substantially influence the catalytic product selectivity of Cu oxide NPs.

  7. QSAR ligand dataset for modelling mutagenicity, genotoxicity, and rodent carcinogenicity

    Directory of Open Access Journals (Sweden)

    Davy Guan

    2018-04-01

    Full Text Available Five datasets were constructed from ligand and bioassay result data from the literature. These datasets include bioassay results from the Ames mutagenicity assay, Greenscreen GADD-45a-GFP assay, Syrian Hamster Embryo (SHE assay, and 2 year rat carcinogenicity assay results. These datasets provide information about chemical mutagenicity, genotoxicity and carcinogenicity.

  8. Designer Ligands. Part 13. Synthesis and Catalytic Activity of ...

    African Journals Online (AJOL)

    Copper(I), copper(II), cobalt(II) and zinc(II) complexes of a macrocyclic, multidentate Schiff-base ligand have been prepared and, with the exception of the zinc(II) complex, have been shown to exhibit biomimetic catecholase activity. Keywords: Copper(II);Cobalt(II); Zinc(II); Biomimetic complexes; Catecholase activity

  9. Fas Ligand Expression in Lynch Syndrome-Associated Colorectal Tumours

    NARCIS (Netherlands)

    Koornstra, Jan J.; de Jong, Steven; Boersma-van Eck, Wietske; Zwart, Nynke; Hollema, Harry; de Vries, Elisabeth G. E.; Kleibeuker, Jan H.

    Fas Ligand (FasL) expression by cancer cells may contribute to tumour immune escape via the Fas counterattack against tumour-infiltrating lymphocytes (TILs). Whether this plays a role in colorectal carcinogenesis in Lynch syndrome was examined studying FasL expression, tumour cell apoptosis and

  10. Speciation of Zinc Mixed Ligand Complexes in Salt Water Systems ...

    African Journals Online (AJOL)

    Speciation of Zinc Mixed Ligand Complexes in Salt Water Systems. ... method has been used to study heavy metal interaction in model lake water in KNO3 ... is of no consequential effect because in its normal state, the [OH-] of the lake water is ...

  11. Water-soluble diphosphadiazacyclooctanes as ligands for aqueous organometallic catalysis

    KAUST Repository

    Boulanger, Jé rô me; Bricout, Hervé ; Tilloy, Sé bastien; Fihri, Aziz; Len, Christophe; Hapiot, Fré dé ric; Monflier, É ric

    2012-01-01

    Two new water-soluble diphosphacyclooctanes been synthesized and characterized by NMR and surface tension measurements. Both phosphanes proved to coordinate rhodium in a very selective way as well-defined bidentates were obtained. When used in Rh-catalyzed hydroformylation of terminal alkenes, both ligands positively impacted the reaction chemoselectivity. © 2012 Elsevier B.V.

  12. Iron(III) complexes of certain tetradentate phenolate ligands as ...

    Indian Academy of Sciences (India)

    non-heme iron enzymes, which catalyse the oxidative cleavage of catechols to cis, cis-muconic acids with the incorporation of ... nature of heterocyclic rings of the ligands and the methyl substituents on them regulate the electronic spectral features .... and simple substitution reactions.19,21 The complexes of [H2(L5)] and ...

  13. Trapping of palindromic ligands within native transthyretin prevents amyloid formation

    Science.gov (United States)

    Kolstoe, Simon E.; Mangione, Palma P.; Bellotti, Vittorio; Taylor, Graham W.; Tennent, Glenys A.; Deroo, Stéphanie; Morrison, Angus J.; Cobb, Alexander J. A.; Coyne, Anthony; McCammon, Margaret G.; Warner, Timothy D.; Mitchell, Jane; Gill, Raj; Smith, Martin D.; Ley, Steven V.; Robinson, Carol V.; Wood, Stephen P.; Pepys, Mark B.

    2010-01-01

    Transthyretin (TTR) amyloidosis is a fatal disease for which new therapeutic approaches are urgently needed. We have designed two palindromic ligands, 2,2'-(4,4'-(heptane-1,7-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (mds84) and 2,2'-(4,4'-(undecane-1,11-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (4ajm15), that are rapidly bound by native wild-type TTR in whole serum and even more avidly by amyloidogenic TTR variants. One to one stoichiometry, demonstrable in solution and by MS, was confirmed by X-ray crystallographic analysis showing simultaneous occupation of both T4 binding sites in each tetrameric TTR molecule by the pair of ligand head groups. Ligand binding by native TTR was irreversible under physiological conditions, and it stabilized the tetrameric assembly and inhibited amyloidogenic aggregation more potently than other known ligands. These superstabilizers are orally bioavailable and exhibit low inhibitory activity against cyclooxygenase (COX). They offer a promising platform for development of drugs to treat and prevent TTR amyloidosis. PMID:21059958

  14. Plant twitter: ligands under 140 amino acids enforcing stomatal patterning.

    Science.gov (United States)

    Rychel, Amanda L; Peterson, Kylee M; Torii, Keiko U

    2010-05-01

    Stomata are an essential land plant innovation whose patterning and density are under genetic and environmental control. Recently, several putative ligands have been discovered that influence stomatal density, and they all belong to the epidermal patterning factor-like family of secreted cysteine-rich peptides. Two of these putative ligands, EPF1 and EPF2, are expressed exclusively in the stomatal lineage cells and negatively regulate stomatal density. A third, EPFL6 or CHALLAH, is also a negative regulator of density, but is expressed subepidermally in the hypocotyl. A fourth, EPFL9 or STOMAGEN, is expressed in the mesophyll tissues and is a positive regulator of density. Genetic evidence suggests that these ligands may compete for the same receptor complex. Proper stomatal patterning is likely to be an intricate process involving ligand competition, regional specificity, and communication between tissue layers. EPFL-family genes exist in the moss Physcomitrella patens, the lycophyte Selaginella moellendorffii, and rice, Oryza sativa, and their sequence analysis yields several genes some of which are related to EPF1, EPF2, EPFL6, and EPFL9. Presence of these EPFL family members in the basal land plants suggests an exciting hypothesis that the genetic components for stomatal patterning originated early in land plant evolution.

  15. Colloidal-quantum-dot photovoltaics using atomic-ligand passivation

    KAUST Repository

    Tang, Jiang

    2011-09-18

    Colloidal-quantum-dot (CQD) optoelectronics offer a compelling combination of solution processing and spectral tunability through quantum size effects. So far, CQD solar cells have relied on the use of organic ligands to passivate the surface of the semiconductor nanoparticles. Although inorganic metal chalcogenide ligands have led to record electronic transport parameters in CQD films, no photovoltaic device has been reported based on such compounds. Here we establish an atomic ligand strategy that makes use of monovalent halide anions to enhance electronic transport and successfully passivate surface defects in PbS CQD films. Both time-resolved infrared spectroscopy and transient device characterization indicate that the scheme leads to a shallower trap state distribution than the best organic ligands. Solar cells fabricated following this strategy show up to 6% solar AM1.5G power-conversion efficiency. The CQD films are deposited at room temperature and under ambient atmosphere, rendering the process amenable to low-cost, roll-by-roll fabrication. © 2011 Macmillan Publishers Limited. All rights reserved.

  16. : Recyclable, ligand free palladium(II) catalyst for Heck reaction

    Indian Academy of Sciences (India)

    well as heterogeneous palladium catalysts, generated from either palladium(0) compounds or palladium(II) acetate or chloride salts.6 Several ligands such as phosphines, phoshites, carbenes, thioethers have been successfully employed for this reaction.7 However, homogeneous catalysis results in problems of recovery.

  17. Group 4 Metal Complexes of Chelating Cyclopentadienyl-ketimide Ligands

    Czech Academy of Sciences Publication Activity Database

    Večeřa, M.; Varga, Vojtěch; Císařová, I.; Pinkas, Jiří; Kucharczyk, P.; Sedlařík, V.; Lamač, Martin

    2016-01-01

    Roč. 35, č. 5 (2016), s. 785-798 ISSN 0276-7333 R&D Projects: GA ČR(CZ) GA14-08531S; GA MŠk(CZ) LO1504 Institutional support: RVO:61388955 Keywords : group 4 metal complexes * cyclopentadienyl-ketimide ligands * metallocenes Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.862, year: 2016

  18. Identification of VDR Antagonists among Nuclear Receptor Ligands Using Virtual Screening

    Directory of Open Access Journals (Sweden)

    Kelly Teske

    2014-04-01

    Full Text Available Herein, we described the development of two virtual screens to identify new vitamin D receptor (VDR antagonists among nuclear receptor (NR ligands. Therefore, a database of 14330 nuclear receptor ligands and their NR affinities was assembled using the online available “Binding Database.” Two different virtual screens were carried out in conjunction with a reported VDR crystal structure applying a stringent and less stringent pharmacophore model to filter docked NR ligand conformations. The pharmacophore models were based on the spatial orientation of the hydroxyl functionalities of VDR's natural ligands 1,25(OH2D3 and 25(OH2D3. The first virtual screen identified 32 NR ligands with a calculated free energy of VDR binding of more than -6.0 kJ/mol. All but nordihydroguaiaretic acid (NDGA are VDR ligands, which inhibited the interaction between VDR and coactivator peptide SRC2-3 with an IC50 value of 15.8 μM. The second screen identified 162 NR ligands with a calculated free energy of VDR binding of more than -6.0 kJ/mol. More than half of these ligands were developed to bind VDR followed by ERα/β ligands (26%, TRα/β ligands (7%, and LxRα/β ligands (7%. The binding between VDR and ERα ligand H6036 as well as TRα/β ligand triiodothyronine and a homoserine analog thereof was confirmed by fluorescence polarization.

  19. Heterobifunctional crosslinkers for tethering single ligand molecules to scanning probes

    International Nuclear Information System (INIS)

    Riener, Christian K.; Kienberger, Ferry; Hahn, Christoph D.; Buchinger, Gerhard M.; Egwim, Innocent O.C.; Haselgruebler, Thomas; Ebner, Andreas; Romanin, Christoph; Klampfl, Christian; Lackner, Bernd; Prinz, Heino; Blaas, Dieter; Hinterdorfer, Peter; Gruber, Hermann J.

    2003-01-01

    Single molecule recognition force microscopy (SMRFM) is a versatile atomic force microscopy (AFM) method to probe specific interactions of cognitive molecules on the single molecule level. It allows insights to be gained into interaction potentials and kinetic barriers and is capable of mapping interaction sites with nm positional accuracy. These applications require a ligand to be attached to the AFM tip, preferably by a distensible poly(ethylene glycol) (PEG) chain between the measuring tip and the ligand molecule. The PEG chain greatly facilitates specific binding of the ligand to immobile receptor sites on the sample surface. The present study contributes to tip-PEG-ligand tethering in three ways: (i) a convenient synthetic route was found to prepare NH 2 -PEG-COOH which is the key intermediate for long heterobifunctional crosslinkers; (ii) a variety of heterobifunctional PEG derivatives for tip-PEG-ligand linking were prepared from NH 2 -PEG-COOH; (iii) in particular, a new PEG crosslinker with one thiol-reactive end and one terminal nitrilotriacetic acid (NTA) group was synthesized and successfully used to tether His 6 -tagged protein molecules to AFM tips via noncovalent NTA-Ni 2+ -His 6 bridges. The new crosslinker was applied to link a recombinant His 6 -tagged fragment of the very-low density lipoprotein receptor to the AFM tip whereupon specific docking to the capsid of human rhinovirus particles was observed by force microscopy. In a parallel study, the specific interaction of the small GTPase Ran with the nuclear import receptor importin β1 was studied in detail by SMRFM, using the new crosslinker to link His 6 -tagged Ran to the measuring tip [Nat. Struct. Biol. (2003), 10, 553-557

  20. Organic ligand-induced dissolution kinetics of antimony trioxide

    Institute of Scientific and Technical Information of China (English)

    Xingyun Hu; Mengchang He

    2017-01-01

    The influence of low-molecular-weight dissolved organic matter (LMWDOM) on the dissolution rate of Sb2O3 was investigated.Some representative LMWDOMs with carboxyl,hydroxyl,hydrosulfuryl and amidogen groups occurring naturally in the solution were chosen,namely oxalic acid,citric acid,tartaric acid,EDTA,salicylic acid,phthalandione,glycine,thiolactic acid,xylitol,glucose and catechol.These LMWDOMs were dissolved in inert buffers at pH =3.7,6.6 and 8.6 and added to powdered Sb2O3 in a stirred,thermostatted reactor (25℃).The addition of EDTA,tartaric acid,thiolactic acid,citric acid and oxalic acid solutions at pH 3.7 and catechol at pH 8.6 increased the rate of release of antimony.In the 10 mmol/L thiolactic acid solution,up to 97% by mass of the antimony was released after 120 min reaction.There was no effect on the dissolution of Sb2O3 for the other ligands.A weak correlation between dissolution rate with the dissociation constant of ligands and the stability of the dissolved complex was also found.All the results showed that the extent of the promoting effect of ligands on the dissolution of Sb2O3 was not determined by the stability of the dissolved complex,but by the dissociation constant of ligands and detachment rate of surface chelates from the mineral surface.This study can not only help in further understanding the effect of individual low-molecular-weight organic ligands,but also provides a reference to deduce the effect of natural organic matters with oxygen-bearing functional groups on the dissolution of antimony oxide minerals.

  1. Organic ligand-induced dissolution kinetics of antimony trioxide.

    Science.gov (United States)

    Hu, Xingyun; He, Mengchang

    2017-06-01

    The influence of low-molecular-weight dissolved organic matter (LMWDOM) on the dissolution rate of Sb 2 O 3 was investigated. Some representative LMWDOMs with carboxyl, hydroxyl, hydrosulfuryl and amidogen groups occurring naturally in the solution were chosen, namely oxalic acid, citric acid, tartaric acid, EDTA, salicylic acid, phthalandione, glycine, thiolactic acid, xylitol, glucose and catechol. These LMWDOMs were dissolved in inert buffers at pH=3.7, 6.6 and 8.6 and added to powdered Sb 2 O 3 in a stirred, thermostatted reactor (25°C). The addition of EDTA, tartaric acid, thiolactic acid, citric acid and oxalic acid solutions at pH3.7 and catechol at pH8.6 increased the rate of release of antimony. In the 10mmol/L thiolactic acid solution, up to 97% by mass of the antimony was released after 120min reaction. There was no effect on the dissolution of Sb 2 O 3 for the other ligands. A weak correlation between dissolution rate with the dissociation constant of ligands and the stability of the dissolved complex was also found. All the results showed that the extent of the promoting effect of ligands on the dissolution of Sb 2 O 3 was not determined by the stability of the dissolved complex, but by the dissociation constant of ligands and detachment rate of surface chelates from the mineral surface. This study can not only help in further understanding the effect of individual low-molecular-weight organic ligands, but also provides a reference to deduce the effect of natural organic matters with oxygen-bearing functional groups on the dissolution of antimony oxide minerals. Copyright © 2016. Published by Elsevier B.V.

  2. Structural and Electrochemical Consequences of [Cp*] Ligand Protonation.

    Science.gov (United States)

    Peng, Yun; Ramos-Garcés, Mario V; Lionetti, Davide; Blakemore, James D

    2017-09-05

    There are few examples of the isolation of analogous metal complexes bearing [η 5 -Cp*] and [η 4 -Cp*H] (Cp* = pentamethylcyclopentadienyl) complexes within the same metal/ligand framework, despite the relevance of such structures to catalytic applications. Recently, protonation of Cp*Rh(bpy) (bpy = 2,2'-bipyridyl) has been shown to yield a complex bearing the uncommon [η 4 -Cp*H] ligand, rather than generating a [Rh III -H] complex. We now report the purification and isolation of this protonated species, as well as characterization of analogous complexes of 1,10-phenanthroline (phen). Specifically, reaction of Cp*Rh(bpy) or Cp*Rh(phen) with 1 equiv of Et 3 NH + Br - affords rhodium compounds bearing endo-η 4 -pentamethylcyclopentadiene (η 4 -Cp*H) as a ligand. NMR spectroscopy and single-crystal X-ray diffraction studies confirm protonation of the Cp* ligand, rather than formation of metal hydride complexes. Analysis of new structural data and electronic spectra suggests that phen is significantly reduced in Cp*Rh(phen), similar to the case of Cp*Rh(bpy). Backbonding interactions with olefinic motifs are activated by formation of [η 4 -Cp*H]; protonation of [Cp*] stabilizes the low-valent metal center and results in loss of reduced character on the diimine ligands. In accord with these changes in electronic structure, electrochemical studies reveal a distinct manifold of redox processes that are accessible in the [Cp*H] complexes in comparison with their [Cp*] analogues; these processes suggest new applications in catalysis for the complexes bearing endo-η 4 -Cp*H.

  3. Specific ability of sulfur-ligands on removal of 203Hg-labeled organomercury from hemoglobin in comparison with nitrogen-ligands

    International Nuclear Information System (INIS)

    Hojo, Yasuji; Sugiura, Yukio; Tanaka, Hisashi

    1975-01-01

    Removal of 203 Hg-labeled organomercurials, bound to sulfhydryl groups of hemoglobin, by various chelating agents was investigated by the use of equilibrium dialysis. Organomercurials employed were chlormerodrin, methylmercury, ethylmercury and phenylmercury compounds. Higher and more specific effects of the sulfur-ligands, such as penicillamine and glutathione, on removal of organomercurial were found as compared with those of the nitrogen-ligands such as EDTA, glycine and polymethylenediamines. Linear correlation was observed between the degree of organomercury elimination from hemoglobin and the stability constant (log K 1 ) of 1:1 organomercury complex in both the sulfur- and nitrogen-ligand systems and at the same value of log K 1 , the elimination-effect of sulfur-ligands was extremely greater than that of the nitrogen-ligands. The relationship between the average percentage of removal and the Taft's polar substituent constant of organic moiety of the metal was also linear among the organomercury compounds other than chlormerodrin. The average removal percentage by sulfur-ligands increased in the order, ethylmercury>methylmercury>phenylmercury, while that of the nitrogen-ligands was not different among the organomercurials investigated. In addition, direct ligand-exchange reaction between hemoglobin-SH and the ligand coordinating-atom (S or N) against organomercurials rather than Ssub(N2) reaction via the ternary complex, hemoglobin-S-RHg-ligand, is postulated. (auth.)

  4. Ligand flexibility and framework rearrangement in a new family of porous metal-organic frameworks

    DEFF Research Database (Denmark)

    Hawxwell, Samuel M; Espallargas, Guillermo Mínguez; Bradshaw, Darren

    2007-01-01

    Ligand flexibility permits framework rearrangement upon evacuation and gas uptake in a new family of porous MOFs.......Ligand flexibility permits framework rearrangement upon evacuation and gas uptake in a new family of porous MOFs....

  5. Rule of five in 2015 and beyond: Target and ligand structural limitations, ligand chemistry structure and drug discovery project decisions.

    Science.gov (United States)

    Lipinski, Christopher A

    2016-06-01

    The rule of five (Ro5), based on physicochemical profiles of phase II drugs, is consistent with structural limitations in protein targets and the drug target ligands. Three of four parameters in Ro5 are fundamental to the structure of both target and drug binding sites. The chemical structure of the drug ligand depends on the ligand chemistry and design philosophy. Two extremes of chemical structure and design philosophy exist; ligands constructed in the medicinal chemistry synthesis laboratory without input from natural selection and natural product (NP) metabolites biosynthesized based on evolutionary selection. Exceptions to Ro5 are found mostly among NPs. Chemistry chameleon-like behavior of some NPs due to intra-molecular hydrogen bonding as exemplified by cyclosporine A is a strong contributor to NP Ro5 outliers. The fragment derived, drug Navitoclax is an example of the extensive expertise, resources, time and key decisions required for the rare discovery of a non-NP Ro5 outlier. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Iron and Zinc Complexes of Bulky Bis-Imidazole Ligands : Enzyme Mimicry and Ligand-Centered Redox Activity

    NARCIS (Netherlands)

    Folkertsma, E.

    2016-01-01

    The research described in this thesis is directed to the development of cheap and non-toxic iron-based homogeneous catalysts, using enzyme models and redox non-innocent ligands. Inspired by nature, the first approach focuses on the synthesis of structural models of the active site of non-heme iron

  7. Synthesis of novel '4+1' Tc(III)/Re(III) mixed-ligand complexes with dendritically modified ligands

    International Nuclear Information System (INIS)

    Gniazdowska, E.; Kuenstler, J.U.; Stephan, H.; Pietzsch, H.J.

    2006-01-01

    Coordination chemistry of technetium and rhenium attracts a considerable interest due to the nuclear medicine applications of their radionuclides. Inert, so-called '3+1' or '4+1' technetium/rhenium mixed-ligand complexes open a new way to application of 99 mTc/ 188 Re labeled compounds in tumor diagnosis and therapy. In the presented paper, authors describe the synthesis and study of novel 99 mTc/ 188 Re complexes with dendritically functionalized tetradentate (tripodal chelator 2,2',2''-nitrilotris(ethanethiol), NS 3 and carboxyl group-bearing ligand, NS 3 (COOH) 3 ) and monodentate (dendritically modified isocyanide, CN-R(COOMe) 3 and isocyanide-modified peptide, CN-GGY) ligands. To verify the identity of the prepared n.c.a. complexes, non-radioactive analogous '4+1' Re compounds were synthesized. The experimental data show that a dendritic modification of the tetradentate/monodentate ligands changes the complex lipophilicity and does not influence its stability

  8. The synthesis, structures and characterisation of new mixed-ligand manganese and iron complexes with tripodal, tetradentate ligands

    NARCIS (Netherlands)

    van Gorkum, R.; Berding, J.; Mills, A.M.; Kooijman, H.; Tooke, D.M.; Spek, A.L.; Mutikainen, I.; Turpeinen, U.; Reedijk, J.; Bouwman, E.

    2008-01-01

    The preparation of new manganese and iron complexes with the general formula [M(tripod)(anion)] is described, where M = FeIII or MnIII, “tripod” is a dianionic tetradentate tripodal ligand and the anion is a chelating β-diketonate, 8-oxyquinoline or acetate. The synthesis of this type of complexes

  9. One ligand capable of in situ reaction in a mixed-ligand system with two new different frameworks

    KAUST Repository

    Wang, Xiaofang; Wang, Runwei; Liu, Xiaofang; Zhu, Pinwen; Qiu, Shilun

    2017-01-01

    The in situ ligand 2,3-pyrazinedicarboxylic acid (2,3-H2pzdc) mixed with 1,1′-(1,4-butanediyl)bis(benzimidazole) (bbbi) is used to form two coordination polymers ([Cd(2,3-pzdc)(bbbi)] (1) and [Cd2Cl3(2-pzc)(bbbi)2] (2)) under hydrothermal conditions

  10. Radioactive contaminants in the subsurface: the influence of complexing ligands on trace metal speciation

    International Nuclear Information System (INIS)

    Hummel, W.

    2007-01-01

    will become part of the radioactive waste in geological repositories. The worst-case scenario is the instantaneous and complete dissolution and decomposition of the ion exchangers in the cementitious environment and the release of free cyanide. I assessed the effects of cyanide complexation on the speciation and solubility of radionuclides by 'backdoor' calculations. In the course of the review process for the Nagra/PSI TDB, two important gaps in the database were identified: a) experimental data for the system ThO 2 -H 2 O cannot be interpreted by a unique set of thermodynamic constants; b) potentially important thermodynamic constants for mixed carbonatohydroxo complexes of tetravalent actinides are missing because of insufficient experimental data. Both problems have been solved using the 'backdoor approach'. (iii) In the field of natural organics, mainly humic and fulvic acids, we face an ill-defined problem concerning the molecular structure of the ligands. There, I proposed a pragmatic approach for performance assessment purposes, the 'conservative roof' approach, which does not aim to accurately model all experimental data, but allows estimates of maximum effects on metal complexation by humic substances to be calculated. The major effects influencing radionuclide-humate interactions are explored in detail: the metal concentration effect; the pH effect; competition effects. The first two effects are included in the 'conservative roof' approach in a simplified form suitable for performance assessment. The competition effects were explored by the 'backdoor approach' using the 'conservative roof' model and additional thermodynamic information. A worked out case study for a safety analysis of a Swiss geological repository project elucidated all important effects in quantitative terms. This case study may serve as a roadmap for the design of more sophisticated approaches to deal with radionuclide-humate interactions in future performance assessments

  11. Effects of Mutations and Ligands on the Thermostability of the l-Arginine/Agmatine Antiporter AdiC and Deduced Insights into Ligand-Binding of Human l-Type Amino Acid Transporters

    Directory of Open Access Journals (Sweden)

    Hüseyin Ilgü

    2018-03-01

    Full Text Available The l-arginine/agmatine transporter AdiC is a prokaryotic member of the SLC7 family, which enables pathogenic enterobacteria to survive the extremely acidic gastric environment. Wild-type AdiC from Escherichia coli, as well as its previously reported point mutants N22A and S26A, were overexpressed homologously and purified to homogeneity. A size-exclusion chromatography-based thermostability assay was used to determine the melting temperatures (Tms of the purified AdiC variants in the absence and presence of the selected ligands l-arginine (Arg, agmatine, l-arginine methyl ester, and l-arginine amide. The resulting Tms indicated stabilization of AdiC variants upon ligand binding, in which Tms and ligand binding affinities correlated positively. Considering results from this and previous studies, we revisited the role of AdiC residue S26 in Arg binding and proposed interactions of the α-carboxylate group of Arg exclusively with amide groups of the AdiC backbone. In the context of substrate binding in the human SLC7 family member l-type amino acid transporter-1 (LAT1; SLC7A5, an analogous role of S66 in LAT1 to S26 in AdiC is discussed based on homology modeling and amino acid sequence analysis. Finally, we propose a binding mechanism for l-amino acid substrates to LATs from the SLC7 family.

  12. Effects of Mutations and Ligands on the Thermostability of the l-Arginine/Agmatine Antiporter AdiC and Deduced Insights into Ligand-Binding of Human l-Type Amino Acid Transporters.

    Science.gov (United States)

    Ilgü, Hüseyin; Jeckelmann, Jean-Marc; Colas, Claire; Ucurum, Zöhre; Schlessinger, Avner; Fotiadis, Dimitrios

    2018-03-20

    The l-arginine/agmatine transporter AdiC is a prokaryotic member of the SLC7 family, which enables pathogenic enterobacteria to survive the extremely acidic gastric environment. Wild-type AdiC from Escherichia coli, as well as its previously reported point mutants N22A and S26A, were overexpressed homologously and purified to homogeneity. A size-exclusion chromatography-based thermostability assay was used to determine the melting temperatures ( T m s) of the purified AdiC variants in the absence and presence of the selected ligands l-arginine (Arg), agmatine, l-arginine methyl ester, and l-arginine amide. The resulting T m s indicated stabilization of AdiC variants upon ligand binding, in which T m s and ligand binding affinities correlated positively. Considering results from this and previous studies, we revisited the role of AdiC residue S26 in Arg binding and proposed interactions of the α-carboxylate group of Arg exclusively with amide groups of the AdiC backbone. In the context of substrate binding in the human SLC7 family member l-type amino acid transporter-1 (LAT1; SLC7A5), an analogous role of S66 in LAT1 to S26 in AdiC is discussed based on homology modeling and amino acid sequence analysis. Finally, we propose a binding mechanism for l-amino acid substrates to LATs from the SLC7 family.

  13. Standards, options and recommendations: concomitant radio chemotherapy for cancer of the cervix: a critical analysis of the literature and update of SOR; Radiochimiotherapie concomitante dans les cancers du col de l'uterus: analyse critique des donnees et mise a jour des Standards, options et recommandations

    Energy Technology Data Exchange (ETDEWEB)

    Haie-Meder, C.; Lhomme, C. [Institut Gustave Roussy, 94 - Villejuif (France); Fervers, B.; Bataillard, A. [Federation Nationale des Centres de Lutte Contre le Cancer, FNCLCC, 75 - Paris (France); Chauvergne, J. [Institut Bergonie, Centre Regional de Lutte Contre le Cancer, 33 - Bordeaux (France); Fondrinier, E. [Centre de Lutte Contre le Cancer Paul-Papin, 49 - Angers (France); Guastalla, J.P. [Centre de Lutte Contre le Cancer Leon-Berard, 69 - Lyon (France); Resbeut, M. [Institut Paoli-Calmettes, 13 - Marseille (France)

    2000-02-01

    The 'Standards, Options and Recommendations'(SOR) project, started in 1993, is a collaboration between the National Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres (CRLCC) and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. To update, according to the methodology of SOR, the Standards, Options and Recommendations for the management of patients with cancer of the cervix, and in particular, the place of concomitant radio-chemotherapy. Data have been identified by a literature search using Medline (to April 1999) and the personal reference lists of experts. Once the guidelines were defined, the document was submitted for review to independent national and international reviewers and to the medical committees of the CRCC. The principle recommendations concerning the place of radio-chemotherapy in the treatment of cancer of the cervix are 1) the available data shows a significant increase in local control (level of evidence A) and of overall survival (level of evidence B1)following concomitant radio-chemotherapy as compared to radiotherapy alone or the combination of radiotherapy-hydroxyurea. For stages IB, IIA, proximal IIB with bad prognostic factors (tumour size greater than 4 cm and/or invasion of pelvic nodes and/or microscopic invasion of the parametrium) and without lumbo-aortic nodal invasion, concomitant radio-chemotherapy can be considered as standard treatment. This benefit is less clear for stages distal IIB, III and IVA without para-aortic nodal invasion (level of evidence C) and must be confirmed (expert agreement). 2) the toxicity of radio-chemotherapy is essentially hematologic and

  14. Thermodynamic properties of water sorption of jackfruit (Artocarpus heterophyllus Lam. as a function of moisture content Propriedades termodinâmicas de sorção de água da jaca (Artocarpus heterophyllus Lam. em função do teor de umidade

    Directory of Open Access Journals (Sweden)

    Ana Paula Prette

    2013-03-01

    Full Text Available The Jackfruit tree is one of the most significant trees in tropical home gardens and perhaps the most widespread and useful tree in the important genus Artocarpus. The fruit is susceptible to mechanical and biological damage in the mature state, and some people find the aroma of the fruit objectionable, particularly in confined spaces. The dehydration process could be an alternative for the exploitation of this product, and the relationship between moisture content and water activity provides useful information for its processing and storage. The aim of this study was to determine the thermodynamic properties of the water sorption of jackfruit (Artocarpus heterophyllus Lam. as a function of moisture content. Desorption isotherms of the different parts of the jackfruit (pulp, peduncle, mesocarp, peel, and seed were determined at four different temperatures (313.15, 323.15, 333.15, and 343.15 K in a water activity range of 0.02-0.753 using the static gravimetric method. Theoretical and empirical models were used to model the desorption isotherms. An analytical solution of the Clausius-Clapeyron equation was proposed to calculate the isosteric heat of sorption, the differential entropy, and Gibbs' free energy using the Guggenhein-Anderson-de Boer and Oswin models considering the effect of temperature on the hygroscopic equilibrium.A jaqueira é uma das árvores mais significativas nos quintais tropicais e, talvez, a árvore mais importante e útil do gênero Artocarpus. O fruto é suscetível a danos mecânicos e biológicos no estado maduro, e seu aroma é desagradável para algumas pessoas, quando em espaços fechados. O processo de desidratação pode ser uma alternativa para a exploração deste produto, e a relação entre a umidade e a atividade de água fornece informações úteis para seu processamento e armazenamento. O objetivo do trabalho foi determinar as propriedades termodinâmicas de sorção da água em frutos de jaca (Artocarpus

  15. Propiedades termodinámicas de sorción de agua de la pulpa de lulo en polvo con encapsulantes Propriedades termodinâmicas de sorção de água de polpa de lulo em pó com encapsulantes

    Directory of Open Access Journals (Sweden)

    Ana Lúcia Gabas

    2009-12-01

    Full Text Available Datos de humedad de equilibrio de polvo de pulpa de lulo (PL con y sin aditivos - 58% de maltodextrina (MD o 58% de goma Arábiga (GA - fueran determinados en las temperaturas de 20, 30, 40 y 50 °C utilizando el método estático gravimétrico para un rango de actividades de agua entre 0.06 y 0.90. Las isotermas presentaran formato sigmoidal del tipo III, y el modelo de Guggenhein-Anderson-de Boer (GAB fue ajustado satisfactoriamente a los datos experimentales de humedad de equilibrio en función de la actividad de agua. La adición de encapsulantes afecto las isotermas de tal manera que en la misma actividad de agua, las muestras PL + GA y PL + MD presentaron un menor contenido de humedad de equilibrio y no fueron afectadas por la variación de temperatura. Los calores isostéricos de sorción de las pulpas en polvo con encapsulantes fueron mayores (menos negativos con relación a las pulpas de lulo en polvo, sugiriendo la existencia de sitios polares más activos en el producto sin adición de GA o MD. Una relación exponencial empírica fue utilizada para describir la dependencia del calor de sorción con el contenido de humedad del material.Dados de umidade de equilíbrio de polpa de lulo em pó (PL com e sem aditivos - 58% de maltodextrina (MD ou 58% de goma Arábica (GA - foram determinados nas temperaturas de 20, 30, 40 e 50 °C, utilizando-se o método estático gravimétrico numa faixa de atividade de água de 0,06 a 0,90. As isotermas apresentaram formato sigmoidal do tipo III e o modelo de Guggenhein-Anderson-de Boer (GAB ajustou satisfatoriamente os dados experimentais de umidade de equilíbrio em função da atividade de água. A adição de encapsulantes afetou as isotermas de tal maneira que na mesma atividade de água, as amostras PL + GA y PL + MD apresentaram um menor conteúdo de umidade de equilíbrio e não foram afetadas pela variação de temperatura. Os calores isostéricos de sorção das polpas em pó com encapsulantes

  16. Remoção de níquel(II de soluções aquosas pela biomassa Sargassum filipendula em múltiplos ciclos de sorção-dessorção = Removal of nickel (II from aqueous solutions by Sargassum filipendula biomass in multiple cycles of sorption-desorption

    Directory of Open Access Journals (Sweden)

    Araceli Aparecida Seolatto

    2009-01-01

    Full Text Available Foi estudado o desempenho da alga marinha Sargassum filipendula na remoção de níquel de uma solução de concentração de 50 mg L-1 em pH 3,5, em colunas de leito fixo que operam em ciclos de adsorção/dessorção. Foram testados dois sistemas de eluição; oprimeiro operou com a passagem direta e o segundo com a recirculação do eluente. Em seguida, foram realizados dez ciclos consecutivos de sorção-dessorção em duas colunas de leito fixo, uma regenerada com o eluente H2SO4 (0,1 M e outra com MgSO4/H2SO4 (pH 3, em sistema de recirculação do eluente. As etapas de sorção e dessorção foram realizadas em 30 e 2h, respectivamente, representando 20 dias de uso contínuo da biomassa. Foi observada alta quantidade recuperada de níquel nas etapas de eluição (aproximadamente 95%. Ao finaldo décimo ciclo, verificou-se que a alga Sargassum filipendula continuava apresentando valores elevados da capacidade de remoção de níquel da solução, mostrando-se como alternativa eficiente de tratamento de águas residuárias contendo metais. A regeneração dabiomassa apresentou baixo custo, além de ter facilitado o processo de tratamento que dispensou trocas sucessivas da biomassa.The behavior of seaweed Sargassum filipendula during a removal of nickel from a 50 mg L-1 aqueous solution at pH 3.5 in fixed-bed columns operating in adsorption/desorption cycles was studied. Twoelution systems were tested: the first one operating with the direct passage of eluant, and the second one with the solution recycle. Then, ten consecutive sorption-desorption cycles were investigated in two packed-bed columns; the first column was regenerated with H2SO4 (0.1 M, and the second one with MgSO4/H2SO4 (3.5% in pH 3 in an eluant recycle system. The sorption and desorption stages were carried out for about 30 and 2h, respectively, representing 20 days of continuous use of the biomass. A high quantity of recovered nickelwas observed in the elution stages

  17. Laboratory automation of high-quality and efficient ligand-binding assays for biotherapeutic drug development.

    Science.gov (United States)

    Wang, Jin; Patel, Vimal; Burns, Daniel; Laycock, John; Pandya, Kinnari; Tsoi, Jennifer; DeSilva, Binodh; Ma, Mark; Lee, Jean

    2013-07-01

    Regulated bioanalytical laboratories that run ligand-binding assays in support of biotherapeutics development face ever-increasing demand to support more projects with increased efficiency. Laboratory automation is a tool that has the potential to improve both quality and efficiency in a bioanalytical laboratory. The success of laboratory automation requires thoughtful evaluation of program needs and fit-for-purpose strategies, followed by pragmatic implementation plans and continuous user support. In this article, we present the development of fit-for-purpose automation of total walk-away and flexible modular modes. We shared the sustaining experience of vendor collaboration and team work to educate, promote and track the use of automation. The implementation of laboratory automation improves assay performance, data quality, process efficiency and method transfer to CRO in a regulated bioanalytical laboratory environment.

  18. Synthesis and characterization ligand tris-(2-thiosalicylamidoethyl)amine and its iron complexes and indium

    International Nuclear Information System (INIS)

    Guerra-Garcia, Pedro Pablo; Valle Bourrouet, Grettel

    2006-01-01

    The synthesis of coordination chemistry ligand tris-(2-tiosalicilamidoetil)amine is presented within the framework of study of tripod ligands, the corresponding complexes of iron and indium. Also, its spectroscopic characterization by proton magnetic resonance is showed; so the influence of ligand on a redox active metal and an inactive is compared. Electrochemical methods have been used. The presence of sulfur atoms modifies the redox and magnetic behavior of iron ion (III), as has been found in other similar ligands [es

  19. Gene Duplication of the zebrafish kit ligand and partitioning of melanocyte development functions to kit ligand a.

    Directory of Open Access Journals (Sweden)

    Keith A Hultman

    2007-01-01

    Full Text Available The retention of particular genes after the whole genome duplication in zebrafish has given insights into how genes may evolve through partitioning of ancestral functions. We examine the partitioning of expression patterns and functions of two zebrafish kit ligands, kit ligand a (kitla and kit ligand b (kitlb, and discuss their possible coevolution with the duplicated zebrafish kit receptors (kita and kitb. In situ hybridizations show that kitla mRNA is expressed in the trunk adjacent to the notochord in the middle of each somite during stages of melanocyte migration and later expressed in the skin, when the receptor is required for melanocyte survival. kitla is also expressed in other regions complementary to kita receptor expression, including the pineal gland, tail bud, and ear. In contrast, kitlb mRNA is expressed in brain ventricles, ear, and cardinal vein plexus, in regions generally not complementary to either zebrafish kit receptor ortholog. However, like kitla, kitlb is expressed in the skin during stages consistent with melanocyte survival. Thus, it appears that kita and kitla have maintained congruent expression patterns, while kitb and kitlb have evolved divergent expression patterns. We demonstrate the interaction of kita and kitla by morpholino knockdown analysis. kitla morphants, but not kitlb morphants, phenocopy the null allele of kita, with defects for both melanocyte migration and survival. Furthermore, kitla morpholino, but not kitlb morpholino, interacts genetically with a sensitized allele of kita, confirming that kitla is the functional ligand to kita. Last, we examine kitla overexpression in embryos, which results in hyperpigmentation caused by an increase in the number and size of melanocytes. This hyperpigmentation is dependent on kita function. We conclude that following genome duplication, kita and kitla have maintained their receptor-ligand relationship, coevolved complementary expression patterns, and that

  20. O-fucosylation of the notch ligand mDLL1 by POFUT1 is dispensable for ligand function.

    Directory of Open Access Journals (Sweden)

    Julia Müller

    Full Text Available Fucosylation of Epidermal Growth Factor-like (EGF repeats by protein O-fucosyltransferase 1 (POFUT1 in vertebrates, OFUT1 in Drosophila is pivotal for NOTCH function. In Drosophila OFUT1 also acts as chaperone for Notch independent from its enzymatic activity. NOTCH ligands are also substrates for POFUT1, but in Drosophila OFUT1 is not essential for ligand function. In vertebrates the significance of POFUT1 for ligand function and subcellular localization is unclear. Here, we analyze the importance of O-fucosylation and POFUT1 for the mouse NOTCH ligand Delta-like 1 (DLL1. We show by mass spectral glycoproteomic analyses that DLL1 is O-fucosylated at the consensus motif C²XXXX(S/TC³ (where C² and C³ are the second and third conserved cysteines within the EGF repeats found in EGF repeats 3, 4, 7 and 8. A putative site with only three amino acids between the second cysteine and the hydroxy amino acid within EGF repeat 2 is not modified. DLL1 proteins with mutated O-fucosylation sites reach the cell surface and accumulate intracellularly. Likewise, in presomitic mesoderm cells of POFUT1 deficient embryos DLL1 is present on the cell surface, and in mouse embryonic fibroblasts lacking POFUT1 the same relative amount of overexpressed wild type DLL1 reaches the cell surface as in wild type embryonic fibroblasts. DLL1 expressed in POFUT1 mutant cells can activate NOTCH, indicating that POFUT1 is not required for DLL1 function as a Notch ligand.

  1. The complex formation of selected actinides (U, Np, Cm) with microbial ligands

    International Nuclear Information System (INIS)

    Glorius, Maja

    2009-01-01

    One of the urgent tasks in the field of nuclear technology is the final storage of radioactive substances. As a part of the safety requirements the protection of humans and the environment from the danger of radioactive substances in case of the release from the final storage is essential. For performing long-term safety calculations the detailed understanding of the physico-chemical effects and influences which cause the mobilisation and transport of actinides are necessary. The presented work was a discrete part of a project, which was focused on the clarification of the influence of microorganisms on the migration of actinides in case of the release of actinides from a final storage. The influence of microbial produced substances on the mobilisation of selected actinides was studied thereby. The microbial produced substances studied in this project were synthesized by bacteria from the Pseudomonas genus under special conditions. Fluorescent Pseudomonads secrete bacterial pyoverdin-type siderophores with a high potential to complex and transport metals, especially iron(III). The aim of the project was to determine how and under which conditions the bioligands are able to complex also radioactive substances and therefore to transport them. For this work the alpha-emitting actinides uranium, curium and neptunium were chosen because their long-life cycle and their radiotoxicity are a matter of particular interest. This work dealed with the interaction of the actinides U(VI), Np(V) and Cm(III) with model ligands simulating the functionality of the pyoverdins. So, such bioligands can essentially influence the behaviour of actinides in the environment. The results of this work contribute to a better understanding and assessment of the influence of the microbial ligands to the mobilisation and migration of the radionuclides. The outcomes could be used to quantify the actinide-mobilising effect of the bioligands, which are released, for example, in the vicinity of a

  2. Solid-state thermolysis of a fac-rhenium(I) carbonyl complex with a redox non-innocent pincer ligand.

    Science.gov (United States)

    Jurca, Titel; Chen, Wen-Ching; Michel, Sheila; Korobkov, Ilia; Ong, Tiow-Gan; Richeson, Darrin S

    2013-03-25

    The development of rhenium(I) chemistry has been restricted by the limited structural and electronic variability of the common pseudo-octahedral products fac-[ReX(CO)3L2] (L2 = α-diimine). We address this constraint by first preparing the bidentate bis(imino)pyridine complexes [(2,6-{2,6-Me2C6H3N=CPh}2C5H3N)Re(CO)3X] (X = Cl 2, Br 3), which were characterized by spectroscopic and X-ray crystallographic means, and then converting these species into tridentate pincer ligand compounds, [(2,6-{2,6-Me2C6H3N=CPh}2C5H3N)Re(CO)2X] (X = Cl 4, Br 5). This transformation was performed in the solid-state by controlled heating of 2 or 3 above 200 °C in a tube furnace under a flow of nitrogen gas, giving excellent yields (≥95 %). Compounds 4 and 5 define a new coordination environment for rhenium(I) carbonyl chemistry where the metal center is supported by a planar, tridentate pincer-coordinated bis(imino)pyridine ligand. The basic photophysical features of these compounds show significant elaboration in both number and intensity of the d-π* transitions observed in the UV/Vis spec tra relative to the bidentate starting materials, and these spectra were analyzed using time-dependent DFT computations. The redox nature of the bis(imino)pyridine ligand in compounds 2 and 4 was examined by electrochemical analysis, which showed two ligand reduction events and demonstrated that the ligand reduction shifts to a more positive potential when going from bidentate 2 to tridentate 4 (+160 mV for the first reduction step and +90 mV for the second). These observations indicate an increase in electrostatic stabilization of the reduced ligand in the tridentate conformation. Elaboration on this synthetic methodology documented its generality through the preparation of the pseudo-octahedral rhenium(I) triflate complex [(2,6-{2,6-Me2C6H3N=CPh}2C5H3N)Re(CO)2OTf] (7, 93 % yield). Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Screening of ligands for the Ullmann synthesis of electron-rich diaryl ethers.

    Science.gov (United States)

    Otto, Nicola; Opatz, Till

    2012-01-01

    In the search for new ligands for the Ullmann diaryl ether synthesis, permitting the coupling of electron-rich aryl bromides at relatively low temperatures, 56 structurally diverse multidentate ligands were screened in a model system that uses copper iodide in acetonitrile with potassium phosphate as the base. The ligands differed largely in their performance, but no privileged structural class could be identified.

  4. Micro-flow synthesis and structural analysis of sterically crowded diimine ligands with five aryl rings

    Directory of Open Access Journals (Sweden)

    Shinichiro Fuse

    2013-11-01

    Full Text Available Sterically crowded diimine ligands with five aryl rings were prepared in one step in good yields using a micro-flow technique. X-ray crystallographic analysis revealed the detailed structure of the bulky ligands. The nickel complexes prepared from the ligands exerted high polymerization activity in the ethylene homopolymerization and copolymerization of ethylene with polar monomers.

  5. Redox non-innocent ligands: versatile new tools to control catalytic reactions

    NARCIS (Netherlands)

    Lyaskovskyy, V.; de Bruin, B.

    2012-01-01

    In this (tutorial overview) perspective we highlight the use of "redox non-innocent" ligands in catalysis. Two main types of reactivity in which the redox non-innocent ligand is involved can be specified: (A) The redox active ligand participates in the catalytic cycle only by accepting/donating

  6. Flow Cytometry-Based Bead-Binding Assay for Measuring Receptor Ligand Specificity

    NARCIS (Netherlands)

    Sprokholt, Joris K.; Hertoghs, Nina; Geijtenbeek, Teunis B. H.

    2016-01-01

    In this chapter we describe a fluorescent bead-binding assay, which is an efficient and feasible method to measure interaction between ligands and receptors on cells. In principle, any ligand can be coated on fluorescent beads either directly or via antibodies. Binding between ligand-coated beads

  7. Design, Testing and Kinetic Analysis of Bulky Monodentate Phosphorus Ligands in the Mizoroki-Heck Reaction

    NARCIS (Netherlands)

    Dodds, Deborah L.; Boele, Maarten D. K.; van Strijdonck, Gino P. F.; de Vries, Johannes G.; van Leeuwen, Piet W. N. M.; Kamer, Paul C. J.

    A series of new monodentate phosphane ligands 2 have been evaluated in the MizorokiHeck arylation reaction of iodobenzene and styrene and compared with our previously reported ligands, 1, 3 and 4. The concept of rational ligand design is discussed, and we describe how the performance of this new

  8. Phosphorus ligand imaging with two-photon fluorescence spectroscopy: towards rational catalyst immobilization

    NARCIS (Netherlands)

    Marras, F.; Kluwer, A.M.; Siekierzycka, J.R.; Vozza, A.; Brouwer, A.M.; Reek, J.N.H.

    2010-01-01

    Spotless catalysts: Ligand immobilization was studied by two-photon fluorescence microscopy with a fluorescent nixantphos ligand as probe (see picture). In the immobilization process ligand aggregates form in solution and are deposited on the support, where they appear as bright spots in

  9. DMPD: Endogenous ligands of Toll-like receptors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15178705 Endogenous ligands of Toll-like receptors. Tsan MF, Gao B. J Leukoc Biol. ...2004 Sep;76(3):514-9. Epub 2004 Jun 3. (.png) (.svg) (.html) (.csml) Show Endogenous ligands of Toll-like re...ceptors. PubmedID 15178705 Title Endogenous ligands of Toll-like receptors. Authors Tsan MF, Gao B. Publicat

  10. Covalent Coupling of Nanoparticles with Low-Density Functional Ligands to Surfaces via Click Chemistry

    NARCIS (Netherlands)

    Rianasari, I.; de Jong, Machiel Pieter; Huskens, Jurriaan; van der Wiel, Wilfred Gerard

    2013-01-01

    We demonstrate the application of the 1,3-dipolar cycloaddition (“click‿ reaction) to couple gold nanoparticles (Au NPs) functionalized with low densities of functional ligands. The ligand coverage on the citrate-stabilized Au NPs was adjusted by the ligand:Au surface atom ratio, while maintaining

  11. Oxovanadium(IV) complexes with tridentate dibasic schiff base ligands and 2-(2'-pyridyl) benzimidazole

    Energy Technology Data Exchange (ETDEWEB)

    Mohanty, R N; Chakravortty, V; Dash, K C [Utkal Univ., Bhubaneswar (India). Dept. of Chemistry

    1991-05-01

    The present work deals with the monomeric, six-coordinated mixed-ligand complexes of oxovanadium(IV) with dibasic tridentate schiff base ligands(ONO donor set) and the bidentate chelating ligand 2-(2'-pyridyl)benzimidazole (PBH) containing N{sub 2} donor set. (author). 1 tab., 22 refs.

  12. Nickel speciation and complexation kinetics in freshwater by ligand exchange and DPCSV

    NARCIS (Netherlands)

    Han Bin Xue,; Jansen, S.; Prasch, A.; Sigg, L.

    2001-01-01

    A technique of ligand exchange with DMG (dimethylglyoxime) and DPCSV was applied to determine Ni speciation in lake, river, and groundwater samples. The working conditions related to ligand-exchange equilibrium were optimized, and the ligand-exchange kinetics were examined. The observed

  13. Ligand-free, protein-bound technetium-99m. Evidence for tumour localisation

    International Nuclear Information System (INIS)

    Jakovljevic, A.C.; Pojer, P.M.

    1984-11-01

    An hypothesis that cations accumulate in tumours independent of ligand is tested. A preparation of technetium-99m known to be ligand-free (that is, the technetium is protein bound and no other ligand is injected) has been shown to accumulate in a T-cell lymphoma

  14. Interactions between alkaline earth cations and oxo ligands. DFT study of the affinity of the Mg²+ cation for phosphoryl ligands.

    Science.gov (United States)

    da Costa, Leonardo Moreira; de Mesquita Carneiro, José Walkimar; Paes, Lilian Weitzel Coelho

    2011-08-01

    DFT (B3LYP/6-31+G(d)) calculations of Mg(2+) affinities for a set of phosphoryl ligands were performed. Two types of ligands were studied: a set of trivalent [O = P(R)] and a set of pentavalent phosphoryl ligands [O = P(R)(3)] (R = H, F, Cl, Br, OH, OCH(3), CH(3), CN, NH(2) and NO(2)), with R either bound directly to the phosphorus atom or to the para position of a phenyl ring. The affinity of the Mg(2+) cation for the ligands was quantified by means of the enthalpy for the substitution of one water molecule in the [Mg(H(2)O)(6)](2+) complex for a ligand. The enthalpy of substitution was correlated with electronic and geometric parameters. Electron-donor groups increase the interaction between the cation and the ligand, while electron-acceptor groups decrease the interaction enthalpy.

  15. Importance of the pharmacological profile of the bound ligand in enrichment on nuclear receptors: toward the use of experimentally validated decoy ligands.

    Science.gov (United States)

    Lagarde, Nathalie; Zagury, Jean-François; Montes, Matthieu

    2014-10-27

    The evaluation of virtual ligand screening methods is of major importance to ensure their reliability. Taking into account the agonist/antagonist pharmacological profile should improve the quality of the benchmarking data sets since ligand binding can induce conformational changes in the nuclear receptor structure and such changes may vary according to the agonist/antagonist ligand profile. We indeed found that splitting the agonist and antagonist ligands into two separate data sets for a given nuclear receptor target significantly enhances the quality of the evaluation. The pharmacological profile of the ligand bound in the binding site of the target structure was also found to be an additional critical parameter. We also illustrate that active compound data sets for a given pharmacological activity can be used as a set of experimentally validated decoy ligands for another pharmacological activity to ensure a reliable and challenging evaluation of virtual screening methods.

  16. Structural insight into the function of myelin basic protein as a ligand for integrin αMβ2

    DEFF Research Database (Denmark)

    Stapulionis, Romualdas; Oliveira, Cristiano; Gjelstrup, Mikkel Carstensen

    2008-01-01

    protein (MBP), a major autoantigen in MS, is a potent and specific ligand for the integrin αMβ2 (Mac-1, CD11b/CD18) expressed mainly on phagocytic cells. MBP undergoes a dramatic conformational change when liberated from the lipid-rich environment of the myelin sheath. The MS drug glatiramer acetate......Multiple sclerosis (MS) is an inflammatory disease where phagocytic cells infiltrate the nerve tissue and act as terminal agents in destruction of the myelin sheath. However, the mechanism that triggers the ability of these cells to recognize myelin remains obscure. We show that myelin basic...

  17. Binding constants of membrane-anchored receptors and ligands: A general theory corroborated by Monte Carlo simulations.

    Science.gov (United States)

    Xu, Guang-Kui; Hu, Jinglei; Lipowsky, Reinhard; Weikl, Thomas R

    2015-12-28

    Adhesion processes of biological membranes that enclose cells and cellular organelles are essential for immune responses, tissue formation, and signaling. These processes depend sensitively on the binding constant K2D of the membrane-anchored receptor and ligand proteins that mediate adhesion, which is difficult to measure in the "two-dimensional" (2D) membrane environment of the proteins. An important problem therefore is to relate K2D to the binding constant K3D of soluble variants of the receptors and ligands that lack the membrane anchors and are free to diffuse in three dimensions (3D). In this article, we present a general theory for the binding constants K2D and K3D of rather stiff proteins whose main degrees of freedom are translation and rotation, along membranes and around anchor points "in 2D," or unconstrained "in 3D." The theory generalizes previous results by describing how K2D depends both on the average separation and thermal nanoscale roughness of the apposing membranes, and on the length and anchoring flexibility of the receptors and ligands. Our theoretical results for the ratio K2D/K3D of the binding constants agree with detailed results from Monte Carlo simulations without any data fitting, which indicates that the theory captures the essential features of the "dimensionality reduction" due to membrane anchoring. In our Monte Carlo simulations, we consider a novel coarse-grained model of biomembrane adhesion in which the membranes are represented as discretized elastic surfaces, and the receptors and ligands as anchored molecules that diffuse continuously along the membranes and rotate at their anchor points.

  18. What a difference a 5f element makes: trivalent and tetravalent uranium halide complexes supported by one and two bis[2-(diisopropylphosphino)-4-methylphenyl]amido (PNP) ligands.

    Science.gov (United States)

    Cantat, Thibault; Scott, Brian L; Morris, David E; Kiplinger, Jaqueline L

    2009-03-02

    The coordination behavior of the bis[2-(diisopropylphosphino)-4-methylphenyl]amido ligand (PNP) toward UI3(THF)4 and UCl4 has been investigated to access new uranium(III) and uranium(IV) halide complexes supported by one and two PNP ligands. The reaction between (PNP)K (6) and 1 equiv of UI3(THF)4 afforded the trivalent halide complex (PNP)UI2(4-tBu-pyridine)2 (7) in the presence of 4-tert-butylpyridine. The same reaction carried out with UCl4 and no donor ligand gave [(PNP)UCl3]2 (8), in which the uranium coordination sphere in the (PNP)UCl3 unit is completed by a bridging chloride ligand. When UCl4 is reacted with 1 equiv (PNP)K (6) in the presence of THF, trimethylphosphine oxide (TMPO), or triphenylphosphineoxide (TPPO), the tetravalent halide complexes (PNP)UCl3(THF) (9), (PNP)UCl3(TMPO)2 (10), and (PNP)UCl3(TPPO) (11), respectively, are formed in excellent yields. The bis(PNP) complexes of uranium(III), (PNP)2UI (12), and uranium(IV), (PNP)2UCl2 (13), were easily isolated from the analogous reactions between 2 equiv of 6 and UI3(THF)4 or UCl4, respectively. Complexes 12 and 13 represent the first examples of complexes featuring two PNP ligands coordinated to a single metal center. Complexes 7-13 have been characterized by single-crystal X-ray diffraction and 1H and 31P NMR spectroscopy. The X-ray structures demonstrate the ability of the PNP ligand to adopt new coordination modes upon coordination to uranium. The PNP ligand can adopt both pseudo-meridional and pseudo-facial geometries when it is kappa3-(P,N,P) coordinated, depending on the steric demand at the uranium metal center. Additionally, its hemilabile character was demonstrated with an unusual kappa2-(P,N) coordination mode that is maintained in both the solid-state and in solution. Comparison of the structures of the mono(PNP) and bis(PNP) complexes 7, 9, 11-13 with their respective C5Me5 analogues 1-4 undoubtedly show that a more sterically congested environment is provided by the PNP ligand. The

  19. Fetal environment

    International Nuclear Information System (INIS)

    Kinare, Arun

    2008-01-01

    The intrauterine environment has a strong influence on pregnancy outcome. The placenta and the umbilical cord together form the main supply line of the fetus. Amniotic fluid also serves important functions. These three main components decide whether there will be an uneventful pregnancy and the successful birth of a healthy baby. An insult to the intrauterine environment has an impact on the programming of the fetus, which can become evident in later life, mainly in the form of cardiovascular diseases, diabetes, and certain learning disabilities. The past two decades have witnessed major contributions from researchers in this field, who have included ultrasonologists, epidemiologists, neonatologists, and pediatricians. Besides being responsible for these delayed postnatal effects, abnormalities of the placenta, umbilical cord, and amniotic fluid also have associations with structural and chromosomal disorders. Population and race also influence pregnancy outcomes to some extent in certain situations. USG is the most sensitive imaging tool currently available for evaluation of these factors and can offer considerable information in this area. This article aims at reviewing the USG-related developments in this area and the anatomy, physiology, and various pathologies of the placenta, umbilical cord, and the amniotic fluid

  20. The cholinergic ligand binding material of axonal membranes

    International Nuclear Information System (INIS)

    Mautner, H.G.; Coronado, R.; Jumblatt, J.E.

    1986-01-01

    Choline acetyltransferase and acetylcholinesterase, the enzymes responsible for the synthesis and hydrolysis of ACh, are present in nerve fibers. In crustacean peripheral nerves, release of ACh from cut nerve fibers has been demonstrated. Previously closed membrane vesicles have been prepared from lobster walking leg nerve plasma membrane and saturable binding of cholinergic agonsist and antagonists to such membranes have been demonstrated. This paper studies this axonal cholinergic binding material, and elucidates its functions. The binding of tritium-nicotine to lobster nerve plasma membranes was antagonized by a series of cholinergic ligands as well as by a series of local anesthetics. This preparation was capable of binding I 125-alpha-bungarotoxin, a ligand widely believed to be a specific label for nicotinic ACh receptor. The labelling of 50 K petide band with tritium-MBTA following disulfide reduction is illustrated

  1. Derivatized Pentadentate Macrocyclic Ligands and Their Transition Metal Complexes

    Directory of Open Access Journals (Sweden)

    Muhammad S. Khan

    2002-06-01

    Full Text Available The reaction of the pendant hydroxyethyl group in the planar pentadentate macrocyclic ligand,1,11-bis(2’-hydroxyethyl-4,8;12,16;17,21-trinitrilo-1,2,10,11-tetraazacyclohenicosa- 2,4,6,9,12,14,18,20-octaene (L2, derived from the condensation of 2,6-pyridinedialdehyde with 6,6’-bis(2’ hydroxyethylhydrazino -2,2’-bipyridine (L1, has been investigated. Esterification reactions are facile, and the reaction of the hydroxyethyl-substituted macrocycle with thionyl chloride yields a chloroethyl derivative. Metal complexes of the new derivatized macrocyclic ligands L3-6having general formula ML3-6X2.nH2O (M = Mn, Fe, Co, Ni, Cu, Zn are readily prepared.

  2. Programmed death-1 & its ligands: promising targets for cancer immunotherapy.

    Science.gov (United States)

    Shrimali, Rajeev K; Janik, John E; Abu-Eid, Rasha; Mkrtichyan, Mikayel; Khleif, Samir N

    2015-01-01

    Novel strategies for cancer treatment involving blockade of immune inhibitors have shown significant progress toward understanding the molecular mechanism of tumor immune evasion. The preclinical findings and clinical responses associated with programmed death-1 (PD-1) and PD-ligand pathway blockade seem promising, making these targets highly sought for cancer immunotherapy. In fact, the anti-PD-1 antibodies, pembrolizumab and nivolumab, were recently approved by the US FDA for the treatment of unresectable and metastatic melanoma resistant to anticytotoxic T-lymphocyte antigen-4 antibody (ipilimumab) and BRAF inhibitor. Here, we discuss strategies of combining PD-1/PD-ligand interaction inhibitors with other immune checkpoint modulators and standard-of-care therapy to break immune tolerance and induce a potent antitumor activity, which is currently a research area of key scientific pursuit.

  3. Soluble NKG2D ligands: prevalence, release, and functional impact.

    Science.gov (United States)

    Salih, Helmut Rainer; Holdenrieder, Stefan; Steinle, Alexander

    2008-05-01

    Natural Killer (NK) cells are capable to recognize and eliminate malignant cells. Anti-tumor responses of NK cells are promoted by the tumor-associated expression of cell stress-inducible ligands of the activating NK receptor NKG2D. Current evidence suggests that established tumors subvert NKG2D-mediated tumor immunosurveillance by releasing NKG2D ligands (NKG2DL). Release of NKG2DL has been observed in a broad variety of human tumor entities and is thought to interfere with NKG2D-mediated tumor immunity in several ways. Further, levels of soluble NKG2DL (sNKG2DL) were also found to be elevated under various non-malignant conditions, although the functional implications remain largely unclear. Here we review and discuss the available data on the prevalence, release, functional impact, and potential clinical value of sNKG2DL.

  4. Mesoporous organosilica nanotubes containing a chelating ligand in their walls

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xiao; Goto, Yasutomo; Maegawa, Yoshifumi; Inagaki, Shinji, E-mail: inagaki@mosk.tytlabs.co.jp [Toyota Central R and D Laboratories, Inc., Nagakute, Aichi 480-1192 (Japan); Japan Science and Technology Agency (JST)/ACT-C, Nagakute, Aichi, 480-1192 (Japan); Ohsuna, Tetsu [Toyota Central R and D Laboratories, Inc., Nagakute, Aichi 480-1192 (Japan)

    2014-11-01

    We report the synthesis of organosilica nanotubes containing 2,2′-bipyridine chelating ligands within their walls, employing a single-micelle-templating method. These nanotubes have an average pore diameter of 7.8 nm and lengths of several hundred nanometers. UV-vis absorption spectra and scanning transmission electron microscopy observations of immobilized nanotubes with an iridium complex on the bipyridine ligands showed that the 2,2′-bipyridine groups were homogeneously distributed in the benzene-silica walls. The iridium complex, thus, immobilized on the nanotubes exhibited efficient catalytic activity for water oxidation using Ce{sup 4+}, due to the ready access of reactants to the active sites in the nanotubes.

  5. MULTIDENTATE TEREPHTHALAMIDATE AND HYDROXYPYRIDONATE LIGANDS: TOWARDS NEW ORALLY ACTIVE CHELATORS

    Energy Technology Data Exchange (ETDEWEB)

    Abergel, Rebecca J.; Raymond, Kenneth N.

    2011-07-13

    The limitations of current therapies for the treatment of iron overload or radioisotope contamination have stimulated efforts to develop new orally bioavailable iron and actinide chelators. Siderophore-inspired tetradentate, hexadentate and octadentate terephthalamidate and hydroxypyridonate ligands were evaluated in vivo as selective and efficacious iron or actinide chelating agents, with several metal loading and ligand assessment procedures, using {sup 59}Fe, {sup 238}Pu, and {sup 241}Am as radioactive tracers. The compounds presented in this study were compared to commercially available therapeutic sequestering agents [deferoxamine (DFO) for iron and diethylenetriaminepentaacetic acid (DPTA) for actinides] and are unrivaled in terms of affinity, selectivity and decorporation efficacy, which attests to the fact that high metal affinity may overcome the low bioavailability properties commonly associated to multidenticity.

  6. Mesoporous organosilica nanotubes containing a chelating ligand in their walls

    Directory of Open Access Journals (Sweden)

    Xiao Liu

    2014-11-01

    Full Text Available We report the synthesis of organosilica nanotubes containing 2,2′-bipyridine chelating ligands within their walls, employing a single-micelle-templating method. These nanotubes have an average pore diameter of 7.8 nm and lengths of several hundred nanometers. UV-vis absorption spectra and scanning transmission electron microscopy observations of immobilized nanotubes with an iridium complex on the bipyridine ligands showed that the 2,2′-bipyridine groups were homogeneously distributed in the benzene-silica walls. The iridium complex, thus, immobilized on the nanotubes exhibited efficient catalytic activity for water oxidation using Ce4+, due to the ready access of reactants to the active sites in the nanotubes.

  7. Ligand Access Channels in Cytochrome P450 Enzymes: A Review

    Directory of Open Access Journals (Sweden)

    Philippe Urban

    2018-05-01

    Full Text Available Quantitative structure-activity relationships may bring invaluable information on structural elements of both enzymes and substrates that, together, govern substrate specificity. Buried active sites in cytochrome P450 enzymes are connected to the solvent by a network of channels exiting at the distal surface of the protein. This review presents different in silico tools that were developed to uncover such channels in P450 crystal structures. It also lists some of the experimental evidence that actually suggest that these predicted channels might indeed play a critical role in modulating P450 functions. Amino acid residues at the entrance of the channels may participate to a first global ligand recognition of ligands by P450 enzymes before they reach the buried active site. Moreover, different P450 enzymes show different networks of predicted channels. The plasticity of P450 structures is also important to take into account when looking at how channels might play their role.

  8. Sampling and energy evaluation challenges in ligand binding protein design.

    Science.gov (United States)

    Dou, Jiayi; Doyle, Lindsey; Jr Greisen, Per; Schena, Alberto; Park, Hahnbeom; Johnsson, Kai; Stoddard, Barry L; Baker, David

    2017-12-01

    The steroid hormone 17α-hydroxylprogesterone (17-OHP) is a biomarker for congenital adrenal hyperplasia and hence there is considerable interest in development of sensors for this compound. We used computational protein design to generate protein models with binding sites for 17-OHP containing an extended, nonpolar, shape-complementary binding pocket for the four-ring core of the compound, and hydrogen bonding residues at the base of the pocket to interact with carbonyl and hydroxyl groups at the more polar end of the ligand. Eight of 16 designed proteins experimentally tested bind 17-OHP with micromolar affinity. A co-crystal structure of one of the designs revealed that 17-OHP is rotated 180° around a pseudo-two-fold axis in the compound and displays multiple binding modes within the pocket, while still interacting with all of the designed residues in the engineered site. Subsequent rounds of mutagenesis and binding selection improved the ligand affinity to nanomolar range, while appearing to constrain the ligand to a single bound conformation that maintains the same "flipped" orientation relative to the original design. We trace the discrepancy in the design calculations to two sources: first, a failure to model subtle backbone changes which alter the distribution of sidechain rotameric states and second, an underestimation of the energetic cost of desolvating the carbonyl and hydroxyl groups of the ligand. The difference between design model and crystal structure thus arises from both sampling limitations and energy function inaccuracies that are exacerbated by the near two-fold symmetry of the molecule. © 2017 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

  9. Identification and characterization of PPAR? ligands in the hippocampus

    OpenAIRE

    Roy, Avik; Kundu, Madhuchhanda; Jana, Malabendu; Mishra, Rama K.; Yung, Yeni; Luan, Chi-Hao; Gonzalez, Frank J.; Pahan, Kalipada

    2016-01-01

    Peroxisome proliferator-activated receptor alpha (PPAR?) regulates hepatic fatty acid catabolism and mediates the metabolic response to starvation. Recently, we have found that PPAR? is constitutively activated in nuclei of hippocampal neurons and controls plasticity via direct transcriptional activation of CREB. Here, three endogenous ligands of PPAR?, 3-hydroxy-(2,2)-dimethyl butyrate, hexadecanamide, and 9-octadecenamide were discovered in mouse brain hippocampus. Mass spectrometric detect...

  10. Ligand pose and orientational sampling in molecular docking.

    Directory of Open Access Journals (Sweden)

    Ryan G Coleman

    Full Text Available Molecular docking remains an important tool for structure-based screening to find new ligands and chemical probes. As docking ambitions grow to include new scoring function terms, and to address ever more targets, the reliability and extendability of the orientation sampling, and the throughput of the method, become pressing. Here we explore sampling techniques that eliminate stochastic behavior in DOCK3.6, allowing us to optimize the method for regularly variable sampling of orientations. This also enabled a focused effort to optimize the code for efficiency, with a three-fold increase in the speed of the program. This, in turn, facilitated extensive testing of the method on the 102 targets, 22,805 ligands and 1,411,214 decoys of the Directory of Useful Decoys-Enhanced (DUD-E benchmarking set, at multiple levels of sampling. Encouragingly, we observe that as sampling increases from 50 to 500 to 2000 to 5000 to 20,000 molecular orientations in the binding site (and so from about 1×10(10 to 4×10(10 to 1×10(11 to 2×10(11 to 5×10(11 mean atoms scored per target, since multiple conformations are sampled per orientation, the enrichment of ligands over decoys monotonically increases for most DUD-E targets. Meanwhile, including internal electrostatics in the evaluation ligand conformational energies, and restricting aromatic hydroxyls to low energy rotamers, further improved enrichment values. Several of the strategies used here to improve the efficiency of the code are broadly applicable in the field.

  11. Can mixed ligand therapy completely remove plutonium from the body

    Energy Technology Data Exchange (ETDEWEB)

    Volf, V [Kernforschungszentrum Karlsruhe G.m.b.H. (Germany, F.R.). Inst. fuer Genetik und Toxikologie von Spaltstoffen

    1980-08-01

    Results of experiments to determine the effects of mixed ligand chelate treatment on tissue levels of /sup 238/Pu in rats after injection of /sup 238/Pu citrate are presented and discussed. It is concluded that when attempting to remove Pu from the body there seems to be no reason for combining Ca-DTPA, the present chelate of choice, with catechol or Tiron, or with salicylate and its derivatives.

  12. Multiscale simulations of ligand adsorption and exchange on gold nanoparticles.

    Science.gov (United States)

    Gao, Hui-Min; Liu, Hong; Qian, Hu-Jun; Jiao, Gui-Sheng; Lu, Zhong-Yuan

    2018-01-17

    We have developed a multiscale model that combines first-principles methods with atomistic and mesoscopic simulations to explore the molecular structures and packing density of the ligands present on the gold nanoparticle (AuNP) surface, as well as the adsorption/exchange reaction kinetics of cetyltrimethylammonium bromide (CTAB)/PEG-SH ligands on different facets of gold, namely, Au(111), Au(100), and Au(110). Our model predicts that on clean gold surfaces, CTAB adsorption is diffusion limited. Specifically, CTAB has the preferentially higher adsorption rate and coverage density on Au(100) and Au(110) surfaces, forming a more compact layer with respect to that on the Au(111) surface, which could result in greater growth of gold nanoparticles along the (111) direction. As opposed to CTAB adsorption, the exchange reaction between PEG-SH with CTAB shows no selectivity to different crystal faces, and the reaction process follows Langmuir diffusion kinetics. Kinetic analysis reveals that, in water, the exchange reaction is zeroth order with respect to the concentration of an incoming PEG-SH, indicative of a dissociative exchange mechanism. The observed rate constant decreases exponentially with the PEG-SH chain length, consistent with a diffusion process for the free PEG-SH in water. In particular, we show that the exchange efficiency increases as the chain rigidness and size of the incoming ligand and/or steric bulk of the initial protecting ligand shell are decreased. Our objectives are to provide a model to assess the kinetics and thermodynamics of the adsorption/exchange reaction process, and we expect that these findings will have important implications for routine surface characterization of AuNPs.

  13. Ligand mobility modulates immunological synapse formation and T cell activation.

    Directory of Open Access Journals (Sweden)

    Chih-Jung Hsu

    Full Text Available T cell receptor (TCR engagement induces clustering and recruitment to the plasma membrane of many signaling molecules, including the protein tyrosine kinase zeta-chain associated protein of 70 kDa (ZAP70 and the adaptor SH2 domain-containing leukocyte protein of 76 kDa (SLP76. This molecular rearrangement results in formation of the immunological synapse (IS, a dynamic protein array that modulates T cell activation. The current study investigates the effects of apparent long-range ligand mobility on T cell signaling activity and IS formation. We formed stimulatory lipid bilayers on glass surfaces from binary lipid mixtures with varied composition, and characterized these surfaces with respect to diffusion coefficient and fluid connectivity. Stimulatory ligands coupled to these surfaces with similar density and orientation showed differences in their ability to activate T cells. On less mobile membranes, central supramolecular activation cluster (cSMAC formation was delayed and the overall accumulation of CD3ζ at the IS was reduced. Analysis of signaling microcluster (MC dynamics showed that ZAP70 MCs exhibited faster track velocity and longer trajectories as a function of increased ligand mobility, whereas movement of SLP76 MCs was relatively insensitive to this parameter. Actin retrograde flow was observed on all surfaces, but cell spreading and subsequent cytoskeletal contraction were more pronounced on mobile membranes. Finally, increased tyrosine phosphorylation and persistent elevation of intracellular Ca(2+ were observed in cells stimulated on fluid membranes. These results point to ligand mobility as an important parameter in modulating T cell responses.

  14. Nanoparticle-based receptors mimic protein-ligand recognition

    OpenAIRE

    Riccardi, Laura; Gabrielli, Luca; Sun, Xiaohuan; Biasi, Federico De; Rastrelli, Federico; Mancin, Fabrizio; De Vivo, Marco

    2017-01-01

    Summary The self-assembly of a monolayer of ligands on the surface of noble-metal nanoparticles dictates the fundamental nanoparticle's behavior and its functionality. In this combined computational-experimental study, we analyze the structure, organization, and dynamics of functionalized coating thiols in monolayer-protected gold nanoparticles (AuNPs). We explain how functionalized coating thiols self-organize through a delicate and somehow counterintuitive balance of interactions within the...

  15. Sampling protein motion and solvent effect during ligand binding

    Science.gov (United States)

    Limongelli, Vittorio; Marinelli, Luciana; Cosconati, Sandro; La Motta, Concettina; Sartini, Stefania; Mugnaini, Laura; Da Settimo, Federico; Novellino, Ettore; Parrinello, Michele

    2012-01-01

    An exhaustive description of the molecular recognition mechanism between a ligand and its biological target is of great value because it provides the opportunity for an exogenous control of the related process. Very often this aim can be pursued using high resolution structures of the complex in combination with inexpensive computational protocols such as docking algorithms. Unfortunately, in many other cases a number of factors, like protein flexibility or solvent effects, increase the degree of complexity of ligand/protein interaction and these standard techniques are no longer sufficient to describe the binding event. We have experienced and tested these limits in the present study in which we have developed and revealed the mechanism of binding of a new series of potent inhibitors of Adenosine Deaminase. We have first performed a large number of docking calculations, which unfortunately failed to yield reliable results due to the dynamical character of the enzyme and the complex role of the solvent. Thus, we have stepped up the computational strategy using a protocol based on metadynamics. Our approach has allowed dealing with protein motion and solvation during ligand binding and finally identifying the lowest energy binding modes of the most potent compound of the series, 4-decyl-pyrazolo[1,5-a]pyrimidin-7-one. PMID:22238423

  16. Protein-Ligand Empirical Interaction Components for Virtual Screening.

    Science.gov (United States)

    Yan, Yuna; Wang, Weijun; Sun, Zhaoxi; Zhang, John Z H; Ji, Changge

    2017-08-28

    A major shortcoming of empirical scoring functions is that they often fail to predict binding affinity properly. Removing false positives of docking results is one of the most challenging works in structure-based virtual screening. Postdocking filters, making use of all kinds of experimental structure and activity information, may help in solving the issue. We describe a new method based on detailed protein-ligand interaction decomposition and machine learning. Protein-ligand empirical interaction components (PLEIC) are used as descriptors for support vector machine learning to develop a classification model (PLEIC-SVM) to discriminate false positives from true positives. Experimentally derived activity information is used for model training. An extensive benchmark study on 36 diverse data sets from the DUD-E database has been performed to evaluate the performance of the new method. The results show that the new method performs much better than standard empirical scoring functions in structure-based virtual screening. The trained PLEIC-SVM model is able to capture important interaction patterns between ligand and protein residues for one specific target, which is helpful in discarding false positives in postdocking filtering.

  17. MIPs are ancestral ligands for the sex peptide receptor.

    Science.gov (United States)

    Kim, Young-Joon; Bartalska, Katarina; Audsley, Neil; Yamanaka, Naoki; Yapici, Nilay; Lee, Ju-Youn; Kim, Yong-Chul; Markovic, Milica; Isaac, Elwyn; Tanaka, Yoshiaki; Dickson, Barry J

    2010-04-06

    Upon mating, females of many animal species undergo dramatic changes in their behavior. In Drosophila melanogaster, postmating behaviors are triggered by sex peptide (SP), which is produced in the male seminal fluid and transferred to female during copulation. SP modulates female behaviors via sex peptide receptor (SPR) located in a small subset of internal sensory neurons that innervate the female uterus and project to the CNS. Although required for postmating responses only in these female sensory neurons, SPR is expressed broadly in the CNS of both sexes. Moreover, SPR is also encoded in the genomes of insects that lack obvious SP orthologs. These observations suggest that SPR may have additional ligands and functions. Here, we identify myoinhibitory peptides (MIPs) as a second family of SPR ligands that is conserved across a wide range of invertebrate species. MIPs are potent agonists for Drosophila, Aedes, and Aplysia SPRs in vitro, yet are unable to trigger postmating responses in vivo. In contrast to SP, MIPs are not produced in male reproductive organs, and are not required for postmating behaviors in Drosophila females. We conclude that MIPs are evolutionarily conserved ligands for SPR, which are likely to mediate functions other than the regulation of female reproductive behaviors.

  18. Cavity Versus Ligand Shape Descriptors: Application to Urokinase Binding Pockets.

    Science.gov (United States)

    Cerisier, Natacha; Regad, Leslie; Triki, Dhoha; Camproux, Anne-Claude; Petitjean, Michel

    2017-11-01

    We analyzed 78 binding pockets of the human urokinase plasminogen activator (uPA) catalytic domain extracted from a data set of crystallized uPA-ligand complexes. These binding pockets were computed with an original geometric method that does NOT involve any arbitrary parameter, such as cutoff distances, angles, and so on. We measured the deviation from convexity of each pocket shape with the pocket convexity index (PCI). We defined a new pocket descriptor called distributional sphericity coefficient (DISC), which indicates to which extent the protein atoms of a given pocket lie on the surface of a sphere. The DISC values were computed with the freeware PCI. The pocket descriptors and their high correspondences with ligand descriptors are crucial for polypharmacology prediction. We found that the protein heavy atoms lining the urokinases binding pockets are either located on the surface of their convex hull or lie close to this surface. We also found that the radii of the urokinases binding pockets and the radii of their ligands are highly correlated (r = 0.9).

  19. Evolution of ligand specificity in vertebrate corticosteroid receptors

    Directory of Open Access Journals (Sweden)

    Deitcher David L

    2011-01-01

    Full Text Available Abstract Background Corticosteroid receptors include mineralocorticoid (MR and glucocorticoid (GR receptors. Teleost fishes have a single MR and duplicate GRs that show variable sensitivities to mineralocorticoids and glucocorticoids. How these receptors compare functionally to tetrapod MR and GR, and the evolutionary significance of maintaining two GRs, remains unclear. Results We used up to seven steroids (including aldosterone, cortisol and 11-deoxycorticosterone [DOC] to compare the ligand specificity of the ligand binding domains of corticosteroid receptors between a mammal (Mus musculus and the midshipman fish (Porichthys notatus, a teleost model for steroid regulation of neural and behavioral plasticity. Variation in mineralocorticoid sensitivity was considered in a broader phylogenetic context by examining the aldosterone sensitivity of MR and GRs from the distantly related daffodil cichlid (Neolamprologus pulcher, another teleost model for neurobehavioral plasticity. Both teleost species had a single MR and duplicate GRs. All MRs were sensitive to DOC, consistent with the hypothesis that DOC was the initial ligand of the ancestral MR. Variation in GR steroid-specificity corresponds to nine identified amino acid residue substitutions rather than phylogenetic relationships based on receptor sequences. Conclusion The mineralocorticoid sensitivity of duplicate GRs in teleosts is highly labile in the context of their evolutionary phylogeny, a property that likely led to neo-functionalization and maintenance of two GRs.

  20. Reactivity of monoolefin ligand in transition metal complexes

    International Nuclear Information System (INIS)

    Rybinskaya, M.I.

    1978-01-01

    The main tendencies in the coordinated olefin ligand property changes are discussed in the transition metal complexes in comparison with free olefins. The review includes the papers published from 1951 up to 1976. It has been shown that in complexes with transition metal cations olefin π-base acquires the ability to react with nucleophylic reagents. Olefin π-acids in complexes with zero valent metals are easily subjected to electrophylic reagent action. At coordination with transition metal cations the olefin properties are generally preserved, while in the zero-valent metal complexes the nonsaturated ligand acquires the properties of a saturated compounds. The ability of transition metal cations in complexes to intensify reactions of nucleophylic bimolecular substitution of vinyl halogen is clearly detected in contrast to the zero valent metal complexes. It has been shown that investigations of the coordinated olefin ligand reactivity give large possibilities in the further development of the organic synthesis. Some reactions are taken as the basis of important industrial processes

  1. [Supercomputer investigation of the protein-ligand system low-energy minima].

    Science.gov (United States)

    Oferkin, I V; Sulimov, A V; Katkova, E V; Kutov, D K; Grigoriev, F V; Kondakova, O A; Sulimov, V B

    2015-01-01

    The accuracy of the protein-ligand binding energy calculations and ligand positioning is strongly influenced by the choice of the docking target function. This work demonstrates the evaluation of the five different target functions used in docking: functions based on MMFF94 force field and functions based on PM7 quantum-chemical method accounting or without accounting the implicit solvent model (PCM, COSMO or SGB). For these purposes the ligand positions corresponding to the minima of the target function and the experimentally known ligand positions in the protein active site (crystal ligand positions) were compared. Each function was examined on the same test-set of 16 protein-ligand complexes. The new parallelized docking program FLM based on Monte Carlo search algorithm was developed to perform the comprehensive low-energy minima search and to calculate the protein-ligand binding energy. This study demonstrates that the docking target function based on the MMFF94 force field can be used to detect the crystal or near crystal positions of the ligand by the finding the low-energy local minima spectrum of the target function. The importance of solvent accounting in the docking process for the accurate ligand positioning is also shown. The accuracy of the ligand positioning as well as the correlation between the calculated and experimentally determined protein-ligand binding energies are improved when the MMFF94 force field is substituted by the new PM7 method with implicit solvent accounting.

  2. Automated ligand fitting by core-fragment fitting and extension into density

    International Nuclear Information System (INIS)

    Terwilliger, Thomas C.; Klei, Herbert; Adams, Paul D.; Moriarty, Nigel W.; Cohn, Judith D.

    2006-01-01

    An automated ligand-fitting procedure has been developed and tested on 9327 ligands and (F o − F c )exp(iϕ c ) difference density from macromolecular structures in the Protein Data Bank. A procedure for fitting of ligands to electron-density maps by first fitting a core fragment of the ligand to density and then extending the remainder of the ligand into density is presented. The approach was tested by fitting 9327 ligands over a wide range of resolutions (most are in the range 0.8-4.8 Å) from the Protein Data Bank (PDB) into (F o − F c )exp(iϕ c ) difference density calculated using entries from the PDB without these ligands. The procedure was able to place 58% of these 9327 ligands within 2 Å (r.m.s.d.) of the coordinates of the atoms in the original PDB entry for that ligand. The success of the fitting procedure was relatively insensitive to the size of the ligand in the range 10–100 non-H atoms and was only moderately sensitive to resolution, with the percentage of ligands placed near the coordinates of the original PDB entry for fits in the range 58–73% over all resolution ranges tested

  3. Identification and Biological Activity of Synthetic Macrophage Inducible C-Type Lectin Ligands

    Directory of Open Access Journals (Sweden)

    Chriselle D. Braganza

    2018-01-01

    Full Text Available The macrophage inducible C-type lectin (Mincle is a pattern recognition receptor able to recognize both damage-associated and pathogen-associated molecular patterns, and in this respect, there has been much interest in determining the scope of ligands that bind Mincle and how structural modifications to these ligands influence ensuing immune responses. In this review, we will present Mincle ligands of known chemical structure, with a focus on ligands that have been synthetically prepared, such as trehalose glycolipids, glycerol-based ligands, and 6-acylated glucose and mannose derivatives. The ability of the different classes of ligands to influence the innate, and consequently, the adaptive, immune response will be described, and where appropriate, structure–activity relationships within each class of Mincle ligands will be presented.

  4. Organic iron (III) complexing ligands during an iron enrichment experiment in the western subarctic North Pacific

    Science.gov (United States)

    Kondo, Yoshiko; Takeda, Shigenobu; Nishioka, Jun; Obata, Hajime; Furuya, Ken; Johnson, William Keith; Wong, C. S.

    2008-06-01

    Complexation of iron (III) with natural organic ligands was investigated during a mesoscale iron enrichment experiment in the western subarctic North Pacific (SEEDS II). After the iron infusions, ligand concentrations increased rapidly with subsequent decreases. While the increases of ligands might have been partly influenced by amorphous iron colloids formation (12-29%), most in-situ increases were attributable to the Dilution of the fertilized patch may have contributed to the rapid decreases of the ligands. During the bloom decline, ligand concentration increased again, and the high concentrations persisted for 10 days. The conditional stability constant was not different between inside and outside of the fertilized patch. These results suggest that the chemical speciation of the released iron was strongly affected by formation of the ligands; the production of ligands observed during the bloom decline will strongly impact the iron cycle and bioavailability in the surface water.

  5. EXAFS Studies of Some Copper(II) Mixed-Ligand Complexes

    International Nuclear Information System (INIS)

    Joshi, S. K.; Katare, R. K.; Shrivastava, B. D.

    2007-01-01

    X-ray K-absorption spectroscopic studies have been carried out on copper (II) mixed-ligand complexes with glutamic acid and aspartic acid as the primary ligands, where as water, pyridine, imidazole and benz-imidazole have been used as secondary ligands. Chemical shifts obtained from the X-ray absorption data have indicated that the glutamic acid complexes are more ionic as compared to their corresponding aspartic acid complexes having similar secondary ligands. Further, we have estimated the average metal-ligand bond distances from the from structure data. For the different complexes studied under the present investigation, the studies reveal that the bonding parameter α1 decreases with the increase in the percentage covalency of the metal-ligand bond. Thus, the bonding parameter α1 may be used for the estimation of percentage covalency of the metal-ligand bond in other similar complexes

  6. One ligand capable of in situ reaction in a mixed-ligand system with two new different frameworks

    KAUST Repository

    Wang, Xiaofang

    2017-12-24

    The in situ ligand 2,3-pyrazinedicarboxylic acid (2,3-H2pzdc) mixed with 1,1′-(1,4-butanediyl)bis(benzimidazole) (bbbi) is used to form two coordination polymers ([Cd(2,3-pzdc)(bbbi)] (1) and [Cd2Cl3(2-pzc)(bbbi)2] (2)) under hydrothermal conditions. Complex 1 was obtained in the absence of in situ reaction and 2 was synthesized with 2,3-H2pzdc in situ generating 2-pyrazinecarboxylate (2-pzc−). The structural details reveal that 1 has a 3D framework with dia topology, and 2 is a 2D layer structure and develops a 3D supramolecular structure via strong π⋯π stacking interactions. The ligand effects were compared for the two frameworks. In addition, fluorescence properties and thermal stabilities of 1 and 2 in the solid were studied.

  7. Chiral ligand-protected gold nanoclusters: Considering the optical activity from a viewpoint of ligand dissymmetric field

    Directory of Open Access Journals (Sweden)

    Hiroshi Yao

    2016-10-01

    Full Text Available Chirality is a geometric property of a physical, chemical, or biological object, which is not superimposable on its mirror image. Its significant presence has led to a strong demand in the development of chiral drugs, sensors, catalysts, and photofunctional materials. In recent years, chirality of nanoscale organic/inorganic hybrids has received tremendous attention owing to potential applications in chiral nanotechnology. In particular, with the recent progress in the syntheses and characterizations of atomically precise gold nanoclusters protected by achiral thiolates, atomic level origins of their chirality have been unveiled. On the other hand, chirality or optical activity in metal nanoclusters can also be introduced via the surface chiral ligands, which should be universal for the nanosystems. This tutorial review presents some optically-active metal (gold nanoclusters protected by chiral thiolates or phosphines, and their chiroptical (or circular dichroism; CD properties are discussed mostly from a viewpoint of the ligand dissymmetric field scheme. The examples are the gold nanoclusters protected by (R-/(S-2-phenylpropane-1-thiol, (R-/(S-mercaptosuccinic acid, phenylboronate-D/L-fructose complexes, phosphine sulfonate-ephedrinium ion pairs, or glutathione. Some methodologies for versatile asymmetric transformation and chiroptical controls of the nanocluster compounds are also described. In the dissymmetric field model as the origin of optical activity, the chiroptical responses of the gold nanoclusters are strongly associated with coupled oscillator and/or CD stealing mechanisms based on the concept of induced CD (ICD derived from a perturbation theory, so on this basis, some characteristic features of the observed CD responses of chiral ligand-protected gold nanoclusters are presented in detail. We believe that various kinds of origins of chirality found in ligand-protected gold nanoclusters may provide models for understanding those of

  8. A web server for analysis, comparison and prediction of protein ligand binding sites.

    Science.gov (United States)

    Singh, Harinder; Srivastava, Hemant Kumar; Raghava, Gajendra P S

    2016-03-25

    One of the major challenges in the field of system biology is to understand the interaction between a wide range of proteins and ligands. In the past, methods have been developed for predicting binding sites in a protein for a limited number of ligands. In order to address this problem, we developed a web server named 'LPIcom' to facilitate users in understanding protein-ligand interaction. Analysis, comparison and prediction modules are available in the "LPIcom' server to predict protein-ligand interacting residues for 824 ligands. Each ligand must have at least 30 protein binding sites in PDB. Analysis module of the server can identify residues preferred in interaction and binding motif for a given ligand; for example residues glycine, lysine and arginine are preferred in ATP binding sites. Comparison module of the server allows comparing protein-binding sites of multiple ligands to understand the similarity between ligands based on their binding site. This module indicates that ATP, ADP and GTP ligands are in the same cluster and thus their binding sites or interacting residues exhibit a high level of similarity. Propensity-based prediction module has been developed for predicting ligand-interacting residues in a protein for more than 800 ligands. In addition, a number of web-based tools have been integrated to facilitate users in creating web logo and two-sample between ligand interacting and non-interacting residues. In summary, this manuscript presents a web-server for analysis of ligand interacting residue. This server is available for public use from URL http://crdd.osdd.net/raghava/lpicom .

  9. Analysis of ligand-protein exchange by Clustering of Ligand Diffusion Coefficient Pairs (CoLD-CoP)

    Science.gov (United States)

    Snyder, David A.; Chantova, Mihaela; Chaudhry, Saadia

    2015-06-01

    NMR spectroscopy is a powerful tool in describing protein structures and protein activity for pharmaceutical and biochemical development. This study describes a method to determine weak binding ligands in biological systems by using hierarchic diffusion coefficient clustering of multidimensional data obtained with a 400 MHz Bruker NMR. Comparison of DOSY spectrums of ligands of the chemical library in the presence and absence of target proteins show translational diffusion rates for small molecules upon interaction with macromolecules. For weak binders such as compounds found in fragment libraries, changes in diffusion rates upon macromolecular binding are on the order of the precision of DOSY diffusion measurements, and identifying such subtle shifts in diffusion requires careful statistical analysis. The "CoLD-CoP" (Clustering of Ligand Diffusion Coefficient Pairs) method presented here uses SAHN clustering to identify protein-binders in a chemical library or even a not fully characterized metabolite mixture. We will show how DOSY NMR and the "CoLD-CoP" method complement each other in identifying the most suitable candidates for lysozyme and wheat germ acid phosphatase.

  10. Virtual Ligand Screening Using PL-PatchSurfer2, a Molecular Surface-Based Protein-Ligand Docking Method.

    Science.gov (United States)

    Shin, Woong-Hee; Kihara, Daisuke

    2018-01-01

    Virtual screening is a computational technique for predicting a potent binding compound for a receptor protein from a ligand library. It has been a widely used in the drug discovery field to reduce the efforts of medicinal chemists to find hit compounds by experiments.Here, we introduce our novel structure-based virtual screening program, PL-PatchSurfer, which uses molecular surface representation with the three-dimensional Zernike descriptors, which is an effective mathematical representation for identifying physicochemical complementarities between local surfaces of a target protein and a ligand. The advantage of the surface-patch description is its tolerance on a receptor and compound structure variation. PL-PatchSurfer2 achieves higher accuracy on apo form and computationally modeled receptor structures than conventional structure-based virtual screening programs. Thus, PL-PatchSurfer2 opens up an opportunity for targets that do not have their crystal structures. The program is provided as a stand-alone program at http://kiharalab.org/plps2 . We also provide files for two ligand libraries, ChEMBL and ZINC Drug-like.

  11. Magnetic ligand fishing as a targeting tool for HPLC-HRMS-SPE-NMR: α-glucosidase inhibitory ligands and alkylresorcinol glycosides from Eugenia catharinae

    DEFF Research Database (Denmark)

    Wubshet, Sileshi Gizachew; Brighente, Inês M. C.; Moaddel, Ruin

    2015-01-01

    A bioanalytical platform combining magnetic ligand fishing for α-glucosidase inhibition profiling and HPLC-HRMS-SPE-NMR for structural identification of α-glucosidase inhibitory ligands, both directly from crude plant extracts, is presented. Magnetic beads with N-terminus-coupled α-glucosidase we...

  12. Amino propynyl benzoic acid building block in rigid spacers of divalent ligands binding to the Syk SH2 domains with equally high affinity as the natural ligand

    NARCIS (Netherlands)

    Dekker, Frank J; de Mol, Nico J; Fischer, Marcel J E; Liskamp, Rob M J; Dekker, Frank

    2003-01-01

    The construction of rigid spacers composed of amino propynyl benzoic acid building blocks is described. These spacers were used to link two phosphopeptide ligand sites towards obtaining divalent ligands with a high affinity for Syk tandem SH2 domains, which are important in signal transduction. The

  13. Tuning the Relative Stability and Reactivity of Manganese Dioxygen and Peroxo Intermediates via Systematic Ligand Modification.

    Science.gov (United States)

    Kovacs, Julie A

    2015-10-20

    O bond length, and thus the degree of O–O bond activation, in intermediates for which there is no crystal structure, as long as the ligand environment is approximately the same.

  14. Fish genomes provide novel insights into the evolution of vertebrate secretin receptors and their ligand.

    Science.gov (United States)

    Cardoso, João C R; Félix, Rute C; Trindade, Marlene; Power, Deborah M

    2014-12-01

    The secretin receptor (SCTR) is a member of Class 2 subfamily B1 GPCRs and part of the PAC1/VPAC receptor subfamily. This receptor has long been known in mammals but has only recently been identified in other vertebrates including teleosts, from which it was previously considered to be absent. The ligand for SCTR in mammals is secretin (SCT), an important gastrointestinal peptide, which in teleosts has not yet been isolated, or the gene identified. This study revises the evolutionary model previously proposed for the secretin-GPCRs in metazoan by analysing in detail the fishes, the most successful of the extant vertebrates. All the Actinopterygii genomes analysed and the Chondrichthyes and Sarcopterygii fish possess a SCTR gene that shares conserved sequence, structure and synteny with the tetrapod homologue. Phylogenetic clustering and gene environment comparisons revealed that fish and tetrapod SCTR shared a common origin and diverged early from the PAC1/VPAC subfamily group. In teleosts SCTR duplicated as a result of the fish specific whole genome duplication but in all the teleost genomes analysed, with the exception of tilapia (Oreochromis niloticus), one of the duplicates was lost. The function of SCTR in teleosts is unknown but quantitative PCR revealed that in both sea bass (Dicentrarchus labrax) and tilapia (Oreochromis mossambicus) transcript abundance is high in the gastrointestinal tract suggesting it may intervene in similar processes to those in mammals. In contrast, no gene encoding the ligand SCT was identified in the ray-finned fishes (Actinopterygii) although it was present in the coelacanth (lobe finned fish, Sarcopterygii) and in the elephant shark (holocephalian). The genes in linkage with SCT in tetrapods and coelacanth were also identified in ray-finned fishes supporting the idea that it was lost from their genome. At present SCTR remains an orphan receptor in ray-finned fishes and it will be of interest in the future to establish why SCT was

  15. A Protein Data Bank survey reveals shortening of intermolecular hydrogen bonds in ligand-protein complexes when a halogenated ligand is an H-bond donor.

    Directory of Open Access Journals (Sweden)

    Jarosław Poznański

    Full Text Available Halogen bonding in ligand-protein complexes is currently widely exploited, e.g. in drug design or supramolecular chemistry. But little attention has been directed to other effects that may result from replacement of a hydrogen by a strongly electronegative halogen. Analysis of almost 30000 hydrogen bonds between protein and ligand demonstrates that the length of a hydrogen bond depends on the type of donor-acceptor pair. Interestingly, lengths of hydrogen bonds between a protein and a halogenated ligand are visibly shorter than those estimated for the same family of proteins in complexes with non-halogenated ligands. Taking into account the effect of halogenation on hydrogen bonding is thus important when evaluating structural and/or energetic parameters of ligand-protein complexes. All these observations are consistent with the concept that halogenation increases the acidity of the proximal amino/imino/hydroxyl groups and thus makes them better, i.e. stronger, H-bond donors.

  16. A Protein Data Bank survey reveals shortening of intermolecular hydrogen bonds in ligand-protein complexes when a halogenated ligand is an H-bond donor.

    Science.gov (United States)

    Poznański, Jarosław; Poznańska, Anna; Shugar, David

    2014-01-01

    Halogen bonding in ligand-protein complexes is currently widely exploited, e.g. in drug design or supramolecular chemistry. But little attention has been directed to other effects that may result from replacement of a hydrogen by a strongly electronegative halogen. Analysis of almost 30000 hydrogen bonds between protein and ligand demonstrates that the length of a hydrogen bond depends on the type of donor-acceptor pair. Interestingly, lengths of hydrogen bonds between a protein and a halogenated ligand are visibly shorter than those estimated for the same family of proteins in complexes with non-halogenated ligands. Taking into account the effect of halogenation on hydrogen bonding is thus important when evaluating structural and/or energetic parameters of ligand-protein complexes. All these observations are consistent with the concept that halogenation increases the acidity of the proximal amino/imino/hydroxyl groups and thus makes them better, i.e. stronger, H-bond donors.

  17. Synthesis and spectroscopic behavior of highly luminescent Eu 3+-dibenzoylmethanate (DBM) complexes with sulfoxide ligands

    Science.gov (United States)

    Niyama, E.; Brito, H. F.; Cremona, M.; Teotonio, E. E. S.; Reyes, R.; Brito, G. E. S.; Felinto, M. C. F. C.

    2005-09-01

    In this paper the synthesis, characterization and photoluminescent behavior of the [RE(DBM) 3L 2] complexes (RE = Gd and Eu) with a variety of sulfoxide ligands; L = benzyl sulfoxide (DBSO), methyl sulfoxide (DMSO), phenyl sulfoxide (DPSO) and p-tolyl sulfoxide (PTSO) have been investigated in solid state. The emission spectra of the Eu 3+-β-diketonate complexes show characteristics narrow bands arising from the 5D 0 → 7F J ( J = 0-4) transitions, which are split according to the selection rule for C n, C nv or C s site symmetries. The experimental Judd-Ofelt intensity parameters ( Ω2 and Ω4), radiative ( Arad) and non-radiative ( Anrad) decay rates, and R02 for the europium complexes have been determined and compared. The highest value of Ω2 (61.9 × 10 -20 cm 2) was obtained to the complex with PTSO ligand, indicating that Eu 3+ ion is in the highly polarizable chemical environment. The higher values of the experimental quantum yield ( q) and emission quantum efficiency of the emitter 5D 0 level ( η) for the Eu-complexes with DMSO, DBSO and PTSO sulfoxides suggest that these complexes are promising Light Conversion Molecular Devices (LCMDs). The lower value of quantum yield ( q = 1%), for the hydrated complex [Eu(DBM) 3(H 2O)], indicates that the luminescence quenching occurs via multiphonon relaxation by coupling with the OH-oscillators from water molecule coordinated to rare earth ion. The pure red emission of the Eu-complexes has been confirmed by ( x, y) color coordinates.

  18. Isozyme-specific ligands for O-acetylserine sulfhydrylase, a novel antibiotic target.

    Directory of Open Access Journals (Sweden)

    Francesca Spyrakis

    Full Text Available The last step of cysteine biosynthesis in bacteria and plants is catalyzed by O-acetylserine sulfhydrylase. In bacteria, two isozymes, O-acetylserine sulfhydrylase-A and O-acetylserine sulfhydrylase-B, have been identified that share similar binding sites, although the respective specific functions are still debated. O-acetylserine sulfhydrylase plays a key role in the adaptation of bacteria to the host environment, in the defense mechanisms to oxidative stress and in antibiotic resistance. Because mammals synthesize cysteine from methionine and lack O-acetylserine sulfhydrylase, the enzyme is a potential target for antimicrobials. With this aim, we first identified potential inhibitors of the two isozymes via a ligand- and structure-based in silico screening of a subset of the ZINC library using FLAP. The binding affinities of the most promising candidates were measured in vitro on purified O-acetylserine sulfhydrylase-A and O-acetylserine sulfhydrylase-B from Salmonella typhimurium by a direct method that exploits the change in the cofactor fluorescence. Two molecules were identified with dissociation constants of 3.7 and 33 µM for O-acetylserine sulfhydrylase-A and O-acetylserine sulfhydrylase-B, respectively. Because GRID analysis of the two isoenzymes indicates the presence of a few common pharmacophoric features, cross binding titrations were carried out. It was found that the best binder for O-acetylserine sulfhydrylase-B exhibits a dissociation constant of 29 µM for O-acetylserine sulfhydrylase-A, thus displaying a limited selectivity, whereas the best binder for O-acetylserine sulfhydrylase-A exhibits a dissociation constant of 50 µM for O-acetylserine sulfhydrylase-B and is thus 8-fold selective towards the former isozyme. Therefore, isoform-specific and isoform-independent ligands allow to either selectively target the isozyme that predominantly supports bacteria during infection and long-term survival or to completely block

  19. Do All X-ray Structures of Protein-Ligand Complexes Represent Functional States? EPOR, a Case Study.

    Science.gov (United States)

    Corbett, Michael S P; Mark, Alan E; Poger, David

    2017-02-28

    Based on differences between the x-ray crystal structures of ligand-bound and unbound forms, the activation of the erythropoietin receptor (EPOR) was initially proposed to involve a cross-action scissorlike motion. However, the validity of the motions involved in the scissorlike model has been recently challenged. Here, atomistic molecular dynamics simulations are used to examine the structure of the extracellular domain of the EPOR dimer in the presence and absence of erythropoietin and a series of agonistic or antagonistic mimetic peptides free in solution. The simulations suggest that in the absence of crystal packing effects, the EPOR chains in the different dimers adopt very similar conformations with no clear distinction between the agonist and antagonist-bound complexes. This questions whether the available x-ray crystal structures of EPOR truly represent active or inactive conformations. The study demonstrates the difficulty in using such structures to infer a mechanism of action, especially in the case of membrane receptors where just part of the structure has been considered in addition to potential confounding effects that arise from the comparison of structures in a crystal as opposed to a membrane environment. The work highlights the danger of assigning functional significance to small differences between structures of proteins bound to different ligands in a crystal environment without consideration of the effects of the crystal lattice and thermal motion. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  20. Distinct Iron-binding Ligands in the Upper Water Column at Station ALOHA

    Science.gov (United States)

    Bundy, R.; Boiteau, R.; Repeta, D.

    2016-02-01

    The distribution and chemical properties of iron-binding organic ligands at station ALOHA were examined using a combination of solid phase extraction (SPE) followed by high pressure liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS). HPLC-ICPMS ligand measurements were complemented by competitive ligand exchange adsorptive cathodic stripping voltammetry (CLE-ACSV) analysis using salicylaldoxime as the added ligand. By HPLC-ICPMS, we find enhanced concentrations of distinct naturally-occurring polar iron-binding ligands present at the surface and in the chlorophyll maximum. Lower concentrations were found in the subsurface, where a suite of non-polar ligands was detected. Siderophores were present at the deepest depths sampled at station ALOHA, down to 400m. Incubation studies provided evidence for the production of iron-binding ligands associated with nutrient amended phytoplankton growth in surface waters, and as a result of microbial particle remineralization in the subsurface water column. Ligands classes identified via SPE were then compared to CLE-ACSV ligand measurements, as well as the conditional stability constants measured from model polar and non-polar siderophores, yielding insight to the sources of iron-binding ligands throughout the water column at station ALOHA.

  1. Differential expression of VEGF ligands and receptors in prostate cancer.

    Science.gov (United States)

    Woollard, David J; Opeskin, Kenneth; Coso, Sanja; Wu, Di; Baldwin, Megan E; Williams, Elizabeth D

    2013-05-01

    Prostate cancer disseminates to regional lymph nodes, however the molecular mechanisms responsible for lymph node metastasis are poorly understood. The vascular endothelial growth factor (VEGF) ligand and receptor family have been implicated in the growth and spread of prostate cancer via activation of the blood vasculature and lymphatic systems. The purpose of this study was to comprehensively examine the expression pattern of VEGF ligands and receptors in the glandular epithelium, stroma, lymphatic vasculature and blood vessels in prostate cancer. The localization of VEGF-A, VEGF-C, VEGF-D, VEGF receptor (VEGFR)-1, VEGFR-2, and VEGFR-3 was examined in cancerous and adjacent benign prostate tissue from 52 subjects representing various grades of prostate cancer. Except for VEGFR-2, extensive staining was observed for all ligands and receptors in the prostate specimens. In epithelial cells, VEGF-A and VEGFR-1 expression was higher in tumor tissue compared to benign tissue. VEGF-D and VEGFR-3 expression was significantly higher in benign tissue compared to tumor in the stroma and the endothelium of lymphatic and blood vessels. In addition, the frequency of lymphatic vessels, but not blood vessels, was lower in tumor tissue compared with benign tissue. These results suggest that activation of VEGFR-1 by VEGF-A within the carcinoma, and activation of lymphatic endothelial cell VEGFR-3 by VEGF-D within the adjacent benign stroma may be important signaling mechanisms involved in the progression and subsequent metastatic spread of prostate cancer. Thus inhibition of these pathways may contribute to therapeutic strategies for the management of prostate cancer. Copyright © 2012 Wiley Periodicals, Inc.

  2. The Search for Covalently Ligandable Proteins in Biological Systems

    Directory of Open Access Journals (Sweden)

    Syed Lal Badshah

    2016-09-01

    Full Text Available This commentary highlights the recent article published in Nature, June 2016, titled: “Proteome-wide covalent ligand discovery in native biological systems”. They screened the whole proteome of different human cell lines and cell lysates. Around 700 druggable cysteines in the whole proteome were found to bind the electrophilic fragments in both active and inactive states of the proteins. Their experiment and computational docking results agreed with one another. The usefulness of this study in terms of bringing a change in medicinal chemistry is highlighted here.

  3. Mixed-ligand complexes of dioxouranium(VI)

    International Nuclear Information System (INIS)

    Ahuja, Renu; Dwivedi, K.

    1995-01-01

    A number of mixed ligand complexes of UO 2 2+ ion have been studied with aminopolycarboxylic acids, such as ethylenediaminetetraacetic acid with coordination number (CN) = 6, nitrilotriacetic acid with CN = 4 and iminodiacetic acid with CN = 3. Ethyleneglycol-bis-2-aminoethylether tetraacetic acid (EGTA) is an octadentate aminopolycarboxylic acid and forms stable binary complexes with many metal ions at low pH. In this paper the results obtained for the study of 1:1:1 UO 2 VI -EGTA-aspartic acid/glutamic acid systems are studied. (author). 7 refs., 1 fig., 1 tab

  4. Doping Control Via Molecularly Engineered Surface Ligand Coordination

    KAUST Repository

    Yuan, Mingjian; Zhitomirsky, David; Adinolfi, Valerio; Voznyy, Oleksandr; Kemp, Kyle W.; Ning, Zhijun; Lan, Xinzheng; Xu, Jixian; Kim, Jin Young; Dong, Haopeng; Sargent, Edward H.

    2013-01-01

    A means to control the net doping of a CQD solid is identified via the design of the bidentate ligand crosslinking the material. The strategy does not rely on implementing different atmospheres at different steps in device processing, but instead is a robust strategy implemented in a single processing ambient. We achieve an order of magnitude difference in doping that allows us to build a graded photovoltaic device and maintain high current and voltage at maximum power-point conditions. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Mixed ligand lanthanide complexes with dipivaloylmethane and acetic acid

    International Nuclear Information System (INIS)

    Lyu Fehnkhua; Kuz'mina, N.P.; Mazo, G.N.; Martynenko, L.I.

    1995-01-01

    Methods of elemental, X-ray phase, thermal analyses and infrared spectroscopy were used to characterize solid products, formed in MDpm 3 -HAcet-H-hexane systems (M = Pr, Nd, Eu, Gd, Ho, Er, Yb, HDpm -dipivaloylmethane, HAcet - acetic acid). It was established that prepared mixed ligand complexes (MLC) had MDpm 2 Acet composition for all studied rare earths. Differenced in properties of cerium and yttrium rare earths are manifested in processes of MLC thermal dissociation, proceeding at low pressure and 170 deg C. 6 refs., 4 tabs

  6. Novel types of tripodal CMPO ligands: synthesis and extraction

    Energy Technology Data Exchange (ETDEWEB)

    Janczewski, D. [Twente Univ., Enschede (Netherlands). Lab. of Supramolecular Chemistry and Technology; Inst. of Materials Research and Engineering, Research Link (Singapore); Rawdanowicz, M.; Reinhoudt, D.N.; Verboom, W. [Twente Univ., Enschede (Netherlands). Lab. of Supramolecular Chemistry and Technology; Hill, C.; Martinez, I. [Commissariat a l' Energie Atomique, CEA-Valrho, DRCP/SCPS/LCSE, Bagnols-sur-Ceze (France)

    2008-07-01

    Novel tripodal CMPO ligands having either aryl groups at the N-atom or alkyl groups at the CMPO methylene bridge were prepared in good yields. In the latter case one alkyl group per CMPO moiety was selectively introduced. Extraction studies with Am{sup 3+} and Eu{sup 3+} show that there is an influence of the electronic character of the aryl groups on the extraction. Alkylation of the CMPO methylene group gives rise to a considerable decrease of the D-values (about 100-1000 times), dependent on the bulkiness of the alkyl substituent. (orig.)

  7. Overview of Stabilizing Ligands for Biocompatible Quantum Dot Nanocrystals

    Directory of Open Access Journals (Sweden)

    Aaron Clapp

    2011-11-01

    Full Text Available Luminescent colloidal quantum dots (QDs possess numerous advantages as fluorophores in biological applications. However, a principal challenge is how to retain the desirable optical properties of quantum dots in aqueous media while maintaining biocompatibility. Because QD photophysical properties are directly related to surface states, it is critical to control the surface chemistry that renders QDs biocompatible while maintaining electronic passivation. For more than a decade, investigators have used diverse strategies for altering the QD surface. This review summarizes the most successful approaches for preparing biocompatible QDs using various chemical ligands.

  8. Ligand-directed profiling of organelles with internalizing phage libraries

    Science.gov (United States)

    Dobroff, Andrey S.; Rangel, Roberto; Guzman-Roja, Liliana; Salmeron, Carolina C.; Gelovani, Juri G.; Sidman, Richard L.; Bologa, Cristian G.; Oprea, Tudor I.; Brinker, C. Jeffrey; Pasqualini, Renata; Arap, Wadih

    2015-01-01

    Phage display is a resourceful tool to, in an unbiased manner, discover and characterize functional protein-protein interactions, to create vaccines, and to engineer peptides, antibodies, and other proteins as targeted diagnostic and/or therapeutic agents. Recently, our group has developed a new class of internalizing phage (iPhage) for ligand-directed targeting of organelles and/or to identify molecular pathways within live cells. This unique technology is suitable for applications ranging from fundamental cell biology to drug development. Here we describe the method for generating and screening the iPhage display system, and explain how to select and validate candidate internalizing homing peptide. PMID:25640897

  9. Rapid, radiochemical-ligand binding assay for methotrexate

    International Nuclear Information System (INIS)

    Caston, J.D.

    1976-01-01

    A radiochemical ligand binding assay for methotrexate is provided. A binder factor comprising a partially purified dihydrofolic acid reductase preparation is employed. The binder factor is conveniently prepared by homogenizing a factor containing animal organ such as liver, and extracting with isotonic saline and ammonium sulfate. A binder cofactor, NADPH 2 , is also employed in the binding reaction. The procedure contemplates both direct and sequential assay techniques, and it is not interfered with by vast excesses of many natural folate derivatives. 12 claims, 6 drawing figures

  10. Ligands specify estrogen receptor alpha nuclear localization and degradation

    Directory of Open Access Journals (Sweden)

    Caze-Subra Stéphanie

    2010-12-01

    Full Text Available Abstract Background The estrogen receptor alpha (ERα is found predominately in the nucleus, both in hormone stimulated and untreated cells. Intracellular distribution of the ERα changes in the presence of agonists but the impact of different antiestrogens on the fate of ERα is a matter of debate. Results A MCF-7 cell line stably expressing GFP-tagged human ERα (SK19 cell line was created to examine the localization of ligand-bound GFP-ERα. We combined digitonin-based cell fractionation analyses with fluorescence and immuno-electron microscopy to determine the intracellular distribution of ligand-bound ERα and/or GFP-ERα. Using fluorescence- and electron microscopy we demonstrate that both endogenous ERα and GFP-ERα form numerous nuclear focal accumulations upon addition of agonist, 17β-estradiol (E2, and pure antagonists (selective estrogen regulator disruptor; SERD, ICI 182,780 or RU58,668, while in the presence of partial antagonists (selective estrogen regulator modulator; SERM, 4-hydroxytamoxifen (OHT or RU39,411, diffuse nuclear staining persisted. Digitonin based cell fractionation analyses confirmed that endogenous ERα and GFP-ERα predominantly reside in the nuclear fraction. Overall ERα protein levels were reduced after estradiol treatment. In the presence of SERMs ERα was stabilized in the nuclear soluble fraction, while in the presence of SERDs protein levels decreased drastically and the remaining ERα was largely found in a nuclear insoluble fraction. mRNA levels of ESR1 were reduced compared to untreated cells in the presence of all ligands tested, including E2. E2 and SERDs induced ERα degradation occurred in distinct nuclear foci composed of ERα and the proteasome providing a simple explanation for ERα sequestration in the nucleus. Conclusions Our results indicate that chemical structure of ligands directly affect the nuclear fate and protein turnover of the estrogen receptor alpha independently of their impact on

  11. Ligand-protected gold clusters: the structure, synthesis and applications

    International Nuclear Information System (INIS)

    Pichugina, D A; Kuz'menko, N E; Shestakov, A F

    2015-01-01

    Modern concepts of the structure and properties of atomic gold clusters protected by thiolate, selenolate, phosphine and phenylacetylene ligands are analyzed. Within the framework of the superatom theory, the 'divide and protect' approach and the structure rule, the stability and composition of a cluster are determined by the structure of the cluster core, the type of ligands and the total number of valence electrons. Methods of selective synthesis of gold clusters in solution and on the surface of inorganic composites based, in particular, on the reaction of Au n with RS, RSe, PhC≡C, Hal ligands or functional groups of proteins, on stabilization of clusters in cavities of the α-, β and γ-cyclodextrin molecules (Au 15 and Au 25 ) and on anchorage to a support surface (Au 25 /SiO 2 , Au 20 /C, Au 10 /FeO x ) are reviewed. Problems in this field are also discussed. Among the methods for cluster structure prediction, particular attention is given to the theoretical approaches based on the density functional theory (DFT). The structures of a number of synthesized clusters are described using the results obtained by X-ray diffraction analysis and DFT calculations. A possible mechanism of formation of the SR(AuSR) n 'staple' units in the cluster shell is proposed. The structure and properties of bimetallic clusters M x Au n L m (M=Pd, Pt, Ag, Cu) are discussed. The Pd or Pt atom is located at the centre of the cluster, whereas Ag and Cu atoms form bimetallic compounds in which the heteroatom is located on the surface of the cluster core or in the 'staple' units. The optical properties, fluorescence and luminescence of ligand-protected gold clusters originate from the quantum effects of the Au atoms in the cluster core and in the oligomeric SR(AuSR) x units in the cluster shell. Homogeneous and heterogeneous reactions catalyzed by atomic gold clusters are discussed in the context of the reaction mechanism and the nature of the active

  12. Coordination Networks Based on Boronate and Benzoxaborolate Ligands

    Directory of Open Access Journals (Sweden)

    Saad Sene

    2016-05-01

    Full Text Available Despite the extensive range of investigations on boronic acids (R-B(OH2, some aspects of their reactivity still need to be explored. This is the case for the coordination chemistry of boronate anions (R-B(OH3−, which has only recently been started to be studied. The purpose of this review is to summarize some of the key features of boronate ligands (and of their cyclic derivatives, benzoxaborolates in materials: (i coordination properties; (ii spectroscopic signatures; and (iii emerging applications.

  13. Ligand-protected gold clusters: the structure, synthesis and applications

    Science.gov (United States)

    Pichugina, D. A.; Kuz'menko, N. E.; Shestakov, A. F.

    2015-11-01

    Modern concepts of the structure and properties of atomic gold clusters protected by thiolate, selenolate, phosphine and phenylacetylene ligands are analyzed. Within the framework of the superatom theory, the 'divide and protect' approach and the structure rule, the stability and composition of a cluster are determined by the structure of the cluster core, the type of ligands and the total number of valence electrons. Methods of selective synthesis of gold clusters in solution and on the surface of inorganic composites based, in particular, on the reaction of Aun with RS, RSe, PhC≡C, Hal ligands or functional groups of proteins, on stabilization of clusters in cavities of the α-, β and γ-cyclodextrin molecules (Au15 and Au25) and on anchorage to a support surface (Au25/SiO2, Au20/C, Au10/FeOx) are reviewed. Problems in this field are also discussed. Among the methods for cluster structure prediction, particular attention is given to the theoretical approaches based on the density functional theory (DFT). The structures of a number of synthesized clusters are described using the results obtained by X-ray diffraction analysis and DFT calculations. A possible mechanism of formation of the SR(AuSR)n 'staple' units in the cluster shell is proposed. The structure and properties of bimetallic clusters MxAunLm (M=Pd, Pt, Ag, Cu) are discussed. The Pd or Pt atom is located at the centre of the cluster, whereas Ag and Cu atoms form bimetallic compounds in which the heteroatom is located on the surface of the cluster core or in the 'staple' units. The optical properties, fluorescence and luminescence of ligand-protected gold clusters originate from the quantum effects of the Au atoms in the cluster core and in the oligomeric SR(AuSR)x units in the cluster shell. Homogeneous and heterogeneous reactions catalyzed by atomic gold clusters are discussed in the context of the reaction mechanism and the nature of the active sites. The bibliography includes 345 references.

  14. Doping Control Via Molecularly Engineered Surface Ligand Coordination

    KAUST Repository

    Yuan, Mingjian

    2013-08-05

    A means to control the net doping of a CQD solid is identified via the design of the bidentate ligand crosslinking the material. The strategy does not rely on implementing different atmospheres at different steps in device processing, but instead is a robust strategy implemented in a single processing ambient. We achieve an order of magnitude difference in doping that allows us to build a graded photovoltaic device and maintain high current and voltage at maximum power-point conditions. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Trapping of palindromic ligands within native transthyretin prevents amyloid formation

    OpenAIRE

    Kolstoe, Simon E.; Mangione, Palma P.; Bellotti, Vittorio; Taylor, Graham W.; Tennent, Glenys A.; Deroo, Stéphanie; Morrison, Angus J.; Cobb, Alexander J. A.; Coyne, Anthony; McCammon, Margaret G.; Warner, Timothy D.; Mitchell, Jane; Gill, Raj; Smith, Martin D.; Ley, Steven V.

    2010-01-01

    Transthyretin (TTR) amyloidosis is a fatal disease for which new therapeutic approaches are urgently needed. We have designed two palindromic ligands, 2,2'-(4,4'-(heptane-1,7-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (mds84) and 2,2'-(4,4'-(undecane-1,11-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (4ajm15), that are rapidly bound by native wild-type TTR in whole serum and even more avidly by amyloidogenic TTR variants. One to one...

  16. Structural basis for AMPA receptor activation and ligand selectivity

    DEFF Research Database (Denmark)

    Hogner, A; Kastrup, Jette Sandholm Jensen; Jin, R

    2002-01-01

    Glutamate is the principal excitatory neurotransmitter within the mammalian CNS, playing an important role in many different functions in the brain such as learning and memory. In this study, a combination of molecular biology, X-ray structure determinations, as well as electrophysiology...... with Br-HIBO and ACPA have allowed us to explain the molecular mechanism behind this selectivity and to identify key residues for ligand recognition. The agonists induce the same degree of domain closure as AMPA, except for Br-HIBO, which shows a slightly lower degree of domain closure. An excellent...

  17. Controlling Nanocrystal Superlattice Symmetry and Shape-Anisotropic Interactions through Variable Ligand Surface Coverage

    KAUST Repository

    Choi, Joshua J.; Bealing, Clive R.; Bian, Kaifu; Hughes, Kevin J.; Zhang, Wenyu; Smilgies, Detlef-M.; Hennig, Richard G.; Engstrom, James R.; Hanrath, Tobias

    2011-01-01

    The assembly of colloidal nanocrystals (NCs) into superstructures with long-range translational and orientational order is sensitive to the molecular interactions between ligands bound to the NC surface. We illustrate how ligand coverage on colloidal PbS NCs can be exploited as a tunable parameter to direct the self-assembly of superlattices with predefined symmetry. We show that PbS NCs with dense ligand coverage assemble into face-centered cubic (fcc) superlattices whereas NCs with sparse ligand coverage assemble into body-centered cubic (bcc) superlattices which also exhibit orientational ordering of NCs in their lattice sites. Surface chemistry characterization combined with density functional theory calculations suggest that the loss of ligands occurs preferentially on {100} than on reconstructed {111} NC facets. The resulting anisotropic ligand distribution amplifies the role of NC shape in the assembly and leads to the formation of superlattices with translational and orientational order. © 2011 American Chemical Society.

  18. In vitro evaluation of biodegradable microspheres with surface-bound ligands.

    Science.gov (United States)

    Keegan, Mark E; Royce, Sara M; Fahmy, Tarek; Saltzman, W Mark

    2006-02-21

    Protein ligands were conjugated to the surface of biodegradable microspheres. These microsphere-ligand conjugates were then used in two in vitro model systems to evaluate the effect of conjugated ligands on microsphere behavior. Microsphere retention in agarose columns was increased by ligands on the microsphere surface specific for receptors on the agarose matrix. In another experiment, conjugating the lectin Ulex europaeus agglutinin 1 to the microsphere surface increased microsphere adhesion to Caco-2 monolayers compared to control microspheres. This increase in microsphere adhesion was negated by co-administration of l-fucose, indicating that the increase in adhesion is due to specific interaction of the ligand with carbohydrate receptors on the cell surface. These results demonstrate that the ligands conjugated to the microspheres maintain their receptor binding activity and are present on the microsphere surface at a density sufficient to target the microspheres to both monolayers and three-dimensional matrices bearing complementary receptors.

  19. Controlling Nanocrystal Superlattice Symmetry and Shape-Anisotropic Interactions through Variable Ligand Surface Coverage

    KAUST Repository

    Choi, Joshua J.

    2011-03-09

    The assembly of colloidal nanocrystals (NCs) into superstructures with long-range translational and orientational order is sensitive to the molecular interactions between ligands bound to the NC surface. We illustrate how ligand coverage on colloidal PbS NCs can be exploited as a tunable parameter to direct the self-assembly of superlattices with predefined symmetry. We show that PbS NCs with dense ligand coverage assemble into face-centered cubic (fcc) superlattices whereas NCs with sparse ligand coverage assemble into body-centered cubic (bcc) superlattices which also exhibit orientational ordering of NCs in their lattice sites. Surface chemistry characterization combined with density functional theory calculations suggest that the loss of ligands occurs preferentially on {100} than on reconstructed {111} NC facets. The resulting anisotropic ligand distribution amplifies the role of NC shape in the assembly and leads to the formation of superlattices with translational and orientational order. © 2011 American Chemical Society.

  20. Charge-Transfer Effects in Ligand Exchange Reactions of Au25 Monolayer-Protected Clusters.

    Science.gov (United States)

    Carducci, Tessa M; Blackwell, Raymond E; Murray, Royce W

    2015-04-16

    Reported here are second-order rate constants of associative ligand exchanges of Au25L18 nanoparticles (L = phenylethanethiolate) of various charge states, measured by proton nuclear magnetic resonance at room temperature and below. Differences in second-order rate constants (M(-1) s(-1)) of ligand exchange (positive clusters ∼1.9 × 10(-5) versus negative ones ∼1.2 × 10(-4)) show that electron depletion retards ligand exchange. The ordering of rate constants between the ligands benzeneselenol > 4-bromobenzene thiol > benzenethiol reveals that exchange is accelerated by higher acidity and/or electron donation capability of the incoming ligand. Together, these observations indicate that partial charge transfer occurs between the nanoparticle and ligand during the exchange and that this is a rate-determining effect in the process.