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Sample records for monodentate arsine ligand

  1. Riding the Wave of Monodentate Ligand Revival: From the A/B Concept to Noncovalent Interactions.

    Science.gov (United States)

    Pignataro, Luca; Gennari, Cesare

    2016-12-01

    The rediscovery of chiral monodentate ligands made in the period 1999-2003 had important consequences in enantioselective transition-metal catalysis, such as the introduction of the A/B concept (i.e., use of monodentate ligand mixtures) and, later, a renewed interest in supramolecular ligands capable of ligand-ligand and ligand-substrate interactions. This Personal Account summarizes the contributions made by our research group in this area in the period 2004-2015, which reflect the abovementioned developments. Within this area, we introduced some original concepts, such as 1) the use of chiral tropos ligand mixtures; 2) the development of new strategies to maximize heterocomplex formation from combinations of simple monodentate ligands; 3) the investigation of new ligand-ligand interactions to achieve selective heterocomplex formation; and 4) the development of highly efficient and synthetically accessible supramolecular ligands. © 2016 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Recent advances in catalytic asymmetric hydrogenation:Renaissance of the monodentate phosphorus ligands

    Institute of Scientific and Technical Information of China (English)

    GUO Hongchao; DING Kuiling; DAI Lixin

    2004-01-01

    The history for the development of chiral phosphorus ligands in catalytic asymmetric hydrogenation is briefly highlighted. This review focuses on the recent advances in the synthesis of the monodentate phosphorus ligands and their applications in catalytic asymmetric hydrogenation. The examples highlighted in this article clearly demonstrated the importance and advantages of monodentate phosphorus ligands, which had been ignored for 30 a and experienced a renaissance at the very beginning of this millennium, particularly in the area of asymmetric hydrogenation.

  3. Design, testing and kinetic analysis of bulky monodentate phosphorus ligands in the Mizoroki-Heck reaction

    NARCIS (Netherlands)

    Dodds, D.L.; Boele, M.D.K.; van Strijdonck, G.P.F.; de Vries, J.G.; van Leeuwen, P.W.N.M.; Kamer, P.C.J.

    2012-01-01

    A series of new monodentate phosphane ligands 2 have been evaluated in the Mizoroki-Heck 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 li

  4. 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.

    2012-01-01

    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 lig

  5. 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

  6. Design, testing and kinetic analysis of bulky monodentate phosphorus ligands in the Mizoroki-Heck reaction

    NARCIS (Netherlands)

    Dodds, D.L.; Boele, M.D.K.; van Strijdonck, G.P.F.; de Vries, J.G.; van Leeuwen, P.W.N.M.; Kamer, P.C.J.

    2012-01-01

    A series of new monodentate phosphane ligands 2 have been evaluated in the Mizoroki-Heck 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

  7. Rhodium-Catalyzed Asymmetric Conjugate Additions of Boronic Acids Using Monodentate Phosphoramidite Ligands

    NARCIS (Netherlands)

    -G Boiteau, J.; Imbos, R.; J. Minnaard, A.; Feringa, B.L.

    2003-01-01

    Monodentate phosphoramidites have been used for the first time as chiral ligands in the Rh-catalyzed enantioselective conjugate addition of arylboronic acids to enones, unsaturated esters, lactones, and nitro alkenes. High reaction rates and ee’s up to 89% have been obtained.

  8. Catalytic Phosphination and Arsination

    Institute of Scientific and Technical Information of China (English)

    Kwong Fuk Yee; Chan Kin Shing

    2004-01-01

    The catalytic, user-friendly phosphination and arsination of aryl halides and triflates by triphenylphosphine and triphenylarsine using palladium catalysts have provided a facile synthesis of functionalized aryl phosphines and arsines in neutral media. Modification of the cynaoarisne yielded optically active N, As ligands which will be screened in various asymmetric catalysis.

  9. First Examples of Improved Catalytic Asymmetric C-C Bond Formation Using the Monodentate Ligand Combination Approach

    NARCIS (Netherlands)

    Duursma, Ate; Hoen, Rob; Schuppan, Julia; Hulst, Ron; Minnaard, Adriaan J.; Feringa, Bernard

    2003-01-01

    Using a combination of chiral monodentate phosphoramidite ligands in the rhodium-catalyzed conjugate addition of boronic acids to three different substrates, we have shown for the first time that the ligand combination approach is applicable for C-C bond formation. Chiral catalysts based on hetero-c

  10. Application of monodentate secondary phosphine oxides, a new class of chiral ligands, in Ir(I)-catalyzed asymmetric imine hydrogenation

    NARCIS (Netherlands)

    Jiang, X.B.; Minnaard, A.J.; Hessen, B.; Feringa, B.L.; Duchateau, A.L.L.; Andrien, J.G.O.; Boogers, J.A.F.; de Vries, J.G.; L. L. Duschateau, A.

    2003-01-01

    Secondary phosphine oxides were prepared from R1PCl2 and R2MgBr, followed by hydrolysis. They were obtained in an enantiopure form by preparative chiral HPLC. These new monodentate ligands were tested in the iridium-catalyzed hydrogenation of imines at 25 bar. Enantioselectivities up to 76% were obt

  11. Pd-catalyzed amidation of aryl chlorides using monodentate biaryl phosphine ligands: a kinetic, computational, and synthetic investigation.

    Science.gov (United States)

    Ikawa, Takashi; Barder, Timothy E; Biscoe, Mark R; Buchwald, Stephen L

    2007-10-31

    We present results on the amidation of aryl halides and sulfonates utilizing a monodentate biaryl phosphine-Pd catalyst. Our results are in accord with a previous report that suggests that the formation of kappa(2)-amidate complexes is deleterious to the effectiveness of a catalyst for this transformation and that their formation can be prevented by the use of appropriate bidentate ligands. We now provide data that suggest that the use of certain monodentate ligands can also prevent the formation of the kappa(2)-amidate complexes and thereby generate more stable catalysts for the amination of aryl chlorides. Furthermore, computational studies shed light on the importance of the key feature(s) of the biaryl phosphines (a methyl group ortho to the phosphorus center) that enable the coupling to occur. The use of ligands that possess a methyl group ortho to the phosphorus center allows a variety of aryl and heteroaryl chlorides with various amides to be coupled in high yield.

  12. Enthalpy of ligand substitution in cis organopalladium complexes with monodentate ligands.

    Science.gov (United States)

    Salas, Gorka; Casares, Juan A; Espinet, Pablo

    2009-10-21

    The enthalpy for the substitution reaction cis-[PdRf(2)(THF)(2)] + 2 L -->cis-[PdRf(2)L(2)] + 2THF (THF = tetrahydrofuran) has been measured in THF by calorimetric methods for Rf = 3,5-dichloro-2,4,6-trifluorophenyl, L = PPh(3), AsPh(3), SbPh(3), PMePh(2), PCyPh(2), PMe(3), AsMePh(2), or L(2) = dppe (1,2-bis(diphenylphosphino)ethane), dppf (1,1'-bis(diphenylphosphino)ferrocene). The values determined show that the substitution enthalpy has a strong dependence on the electronic and steric properties of the ligand. The study of the consecutive substitution reactions cis-[PdRf(2)(THF)(2)] + L -->cis-[PdRf(2)L(THF)] + THF, and cis-[PdRf(2)L(THF)] + L -->cis-[PdRf(2)L(2)] + THF has been carried our for L = PPh(3) and L = PCyPh(2). The first substitution is clearly more favorable for the bulkier leaving ligand, but the second gives practically the same DeltaH value for both cases, indicating that the differences in steric hindrance happen to compensate the electronic differences for both ligands. The X-ray structures of cis-[PdRf(2)(PMePh(2))(2)], cis-[PdRf(2)(dppe)] and cis-[PdRf(2)(dppf)] are reported.

  13. Preparation and photoluminescence enhancement in terbium(III ternary complexes with β-diketone and monodentate auxiliary ligands

    Directory of Open Access Journals (Sweden)

    Devender Singh

    2016-12-01

    Full Text Available A series of new solid ternary complexes of terbium(III ion based on β-diketone ligand acetylacetone (acac and monodentate auxiliary ligands (aqua/urea/triphenylphosphineoxide/pyridine-N-oxide had been prepared. The structural characterizations of synthesized ternary compounds were studied by means of elemental analysis, infrared (IR, and proton nuclear magnetic resonance (NMR spectral techniques. The optical characteristics were investigated with absorption as well as photoluminescence spectroscopy. Thermal behavior of compounds was examined by TGA/DTA analysis and all metal complexes were found to have good thermal stability. The luminescence decay time of complexes were also calculated by monitoring at emission wavelength corresponding to 5D4 → 7F5 transition. A comparative inspection of the luminescent behavior of prepared ternary compounds was performed in order to determine the function of auxiliary ligands in the enhancement of luminescence intensity produced by central terbium(III ion. The color coordinates values suggested that compounds showed bright green emission in visible region in electromagnetic spectrum. Complexes producing green light could play a significant role in the fabrication of efficient light conversion molecular devices for display purposes and lightning systems.

  14. Synthesis of meta-substituted monodentate phosphinite ligands and implication in hydroformylation

    Indian Academy of Sciences (India)

    SATEJ S DESHMUKH; SHAHAJI R GAIKWAD; SWECHCHHA PANDEY; PRAMOD S MALI; SAMIR H CHIKKALI

    2017-08-01

    Synthesis of meta-substituted phosphinite ligands 3,3' (methoxyphosphanediyl) bis (N,Ndiethylaniline) (4a) and methoxybis(3-methoxyphenyl)phosphane (4b), in high yields, has been demonstrated. Typical phosphorus chemical shift between 110–120 ppm, appearance of methoxy protons and corresponding carbon, as well as ESI-MS spectra unambiguously confirmed the existence of phosphinite ligands 4a and 4b. To demonstrate the synthetic usefulness of 4a and 4b, these ligands were tested in the rhodium catalyzed hydroformylation of 1-octene. The diethylamine substituted ligand 4a was found to be highly active, whereas4bwas less reactive but revealed slightly better regioselectivity of 62% under optimized conditions.Additionally, 4a and 4b were found to catalyze the hydroformylation of styrene, 1-undecenol and 1,1-disubstituted functionalolefin, methyl methacrylate. Both the ligands displayed excellent conversion of styrene, and 4b revealed an excellent branch selectivity of 75%. Although 1-undecenol proved to be amenable to hydroformylation (85–90% conversion to aldehyde), both the ligands failed to discriminate between the linear and branched products. Substrate methyl methacrylate proved to be highly challenging and reduced conversion (between 33–42%) was observed under optimized conditions. Ligand 4a was found to be highly selective towards linear aldehyde (81% linear selectivity).

  15. Instant Ligand Libraries. Parallel Synthesis of Monodentate Phosphoramidites and in Situ Screening in Asymmetric Hydrogenation

    NARCIS (Netherlands)

    Lefort, Laurent; Boogers, Jeroen A.F.; Vries, André H.M. de; Vries, Johannes G. de

    2004-01-01

    Chiral phosphoramidites have been identified as excellent ligands for various metal-catalyzed enantioselective transformations. Taking advantage of their easy preparation and modular nature, we designed a fully automated protocol for the parallel preparation of a library of 32 phosphoramidites and i

  16. Enantioselective Rh-catalyzed hydrogenation of N-formyl dehydroamino esters with monodentate phosphoramidite ligands

    NARCIS (Netherlands)

    Panella, L; Aleixandre, AM; Kruidhof, GJ; Robertus, J; Feringa, BL; de Vries, JG; Minnaard, AJ; Aleixandre, Alicia Marco; Kruidhof, Gerlof J.; Feringa, Bernard

    2006-01-01

    Enantioselectivities up to > 99% ee were achieved in the rhodium-catalyzed asymmetric hydrogenation of N-formyl dehydroamino esters using morrodentate phosphoramidites as chiral ligands. The substrates were synthesized by condensation of methyl isocyanoacetate with a range of aldehydes and with

  17. Luminescent single-ion magnets from Lanthanoid(III) complexes with monodentate ketone ligands

    Energy Technology Data Exchange (ETDEWEB)

    Kanetomo, Takuya; Ishida, Takayuki, E-mail: takayuki.ishida@uec.ac.jp [Department of Engineering Science, The University of Electro-Communications, Tokyo (Japan)

    2016-02-01

    We synthesized [Ln{sup III}(hfac){sub 3}(H{sub 2}O)(L)] (abbreviated as Ln-L; Ln = Gd, Tb, Eu; L = DTBK (di-t-butyl ketone), BP (benzophenone)), in which the carbonyl oxygen atom was coordinated to the Ln ion center, despite of such bulky substituents. Their crystal structures were determined by means of X-ray diffraction study. Gd-DTBK is completely isomorphous to the di-t-butyl nitroxide derivative and accordingly can be regarded as a model with the ligand spin masked. The ac magnetic susceptibility measurements on Tb-DTBK and -BP showed frequency dependence, characteristic of single-ion magnets. They also displayed photoluminescence in the solid state at room temperature. The quantum yields of the luminescence of Tb-DTBK and -BP (λ{sub ex} = 360 nm) were improved to 57 and 35%, respectively, from that of the starting material [TbI{sup III}(hfac){sub 3}(H{sub 2}O){sub 2}] (28% at λ{sub ex} = 370 nm). Similarly, the quantum yields for Eu-DTBK and -BP were 8 and 15%, respectively, with λ{sub ex} = 400 nm, while that of the starting material [EuI{sup III}(hfac){sub 3}(H{sub 2}O){sub 2}] was 4% at λ{sub ex}=400 nm.

  18. Conversion of a monodentate amidinate-germylene ligand into chelating imine-germanate ligands (on mononuclear manganese complexes).

    Science.gov (United States)

    Cabeza, Javier A; García-Álvarez, Pablo; Pérez-Carreño, Enrique; Polo, Diego

    2014-08-18

    The unprecedented transformation of a terminal two-electron-donor amidinate-germylene ligand into a chelating three-electron-donor κ(2)-N,Ge-imine-germanate ligand has been achieved by treating the manganese amidinate-germylene complex [MnBr{Ge((i)Pr2bzam)(t)Bu}(CO)4] (1; (i)Pr2bzam = N,N'-bis(isopropyl)benzamidinate) with LiMe or Ag[BF4]. In these reactions, which afford [Mn{κ(2)Ge,N-GeMe((i)Pr2bzam)(t)Bu}(CO)4] (2) and [Mn{κ(2)Ge,N-GeF((i)Pr2bzam)(t)Bu}(CO)4] (3), respectively, the anionic nucleophile, Me(-) or F(-), ends on the Ge atom while an arm of the amidinate fragment migrates from the Ge atom to the Mn atom. In contrast, the reaction of 1 with AgOTf (OTf = triflate) leads to [Mn(OTf){Ge((i)Pr2bzam)(t)Bu}(CO)4] (4), which maintains intact the amidinate-germylene ligand. Complex 4 is very moisture-sensitive, leading to [Mn2{μ-κ(4)Ge2,O2-Ge2(t)Bu2(OH)2O}(CO)8] (5) and [(i)Pr2bzamH2]OTf (6) in wet solvents. In 5, a novel digermanate(II) ligand, [(t)Bu(OH)GeOGe(OH)(t)Bu](2-), doubly bridges two Mn(CO)4 units. The structures of 1-6 have been characterized by spectroscopic (IR, NMR) and single-crystal X-ray diffraction methods.

  19. Synthesis, characterization, DFT calculation and biological activity of square-planar Ni(II) complexes with tridentate PNO ligands and monodentate pseudohalides. Part II.

    Science.gov (United States)

    Milenković, Milica; Pevec, Andrej; Turel, Iztok; Vujčić, Miroslava; Milenković, Marina; Jovanović, Katarina; Gligorijević, Nevenka; Radulović, Siniša; Swart, Marcel; Gruden-Pavlović, Maja; Adaila, Kawther; Cobeljić, Božidar; Anđelković, Katarina

    2014-11-24

    Three square-planar complexes of Ni(II) with condensation derivative of 2-(diphenylphosphino)benzaldehyde and 4-phenylsemicarbazide and monodentate pseudohalides have been synthesized and characterized on the basis of the results of X-ray, NMR and IR spectroscopy and elemental analysis. Investigated complexes exhibited moderate antibacterial and cytotoxic activity. The most pronounced cytotoxic activity (in the range of cisplatin) to HeLa cell line was observed for ligand and all the complexes. Azido complex and ligand induced concentration dependent cell cycle arrest in the S phase, as well as decrease of percentage of cells in G1 phase, without significant increase of apoptotic fraction of cells. The interaction of the azido complex and ligand with CT-DNA results in changes in UV-Vis spectra typical for non-covalent bonding. The observed intrinsic binding constant of azido complex-CT-DNA and ligand-CT-DNA were 3.22 × 10(5) M(-1) and 2.79 × 10(5) M(-1). The results of DNA cleavage experiments showed that azido complex nicked supercoiled plasmid DNA.

  20. Rhenium(V) and technetium(V) nitrido complexes with mixed tridentate π-donor and monodentate π-acceptor ligands.

    Science.gov (United States)

    Boschi, Alessandra; Cazzola, Emiliano; Uccelli, Licia; Pasquali, Micol; Ferretti, Valeria; Bertolasi, Valerio; Duatti, Adriano

    2012-03-01

    Mixed-ligand [M(N)(SNS)(PPh(3))] complexes (M = Tc, Re) (1, 2) were prepared by reaction of the precursor [M(N)Cl(2)(PPh(3))(2)] with ligand 2,2'-dimercaptodiethylamine [H(2)SNS = NH(CH(2)CH(2)SH)(2)] in refluxing dichloromethane/ethanol mixtures. In these compounds, 2,2'-dimercaptodiethylamine acts as a dianionic tridentate chelating ligand bound to the [M≡N](2+) group through the two π-donor deprotonated sulfur atoms and the protonated amine nitrogen atom. Triphenylphosphine completes the coordination sphere, acting as a monodentate ligand. [M(N)(NS(2))(PPh(3))] complexes can assume two different isomeric forms depending on the syn and anti orientations of the hydrogen atom bound to the central nitrogen atom of the SNS ligand with respect to the M≡N moiety. X-ray crystallography of the syn isomer of complex 2 demonstrated that it has a distorted trigonal bipyramidal geometry with the nitrido group and the two sulfur atoms defining the equatorial plane, the phosphorus atom of the monophosphine and the protonated amine nitrogen of the tridentate ligand spanning the two reciprocal trans positions along the axis perpendicular to the trigonal plane. Synthesis of the analogous Tc derivatives with tris(2-cyanoethyl)phosphine, [Tc(N)(SNS)(PCN)] [(PCN = P(CH(2)CH(2)CN)(3)], required the preliminary preparation of the new precursor [Tc(N)(PCN)(2)Cl(2)](2) (3), which was prepared by reacting [n-NBu(4)][Tc(N)Cl(4)] with a high excess of PCN. The crystal structure of compound 3 consists of a noncrystallographic centrosymmetric dimer of Tc(V) nitrido complexes having an octahedral geometry. In this arrangement, the apical positions are occupied by two tris(2-cyanoethyl)phosphine groups and the equatorial positions by the nitrido group whereas the two Cl(-) anions and one cyano ligand belong to the other octahedral component of the dimer. By reacting the new precursor [Tc(N)(PCN)(2)Cl(2)](2) with the ligand H(2)SNS the complex [Tc(N)(SNS)(PCN)] (5) was finally obtained in

  1. A Novel Copper(Ⅱ) Coordination Polymer with Figure-of-eight-shaped Channels Occupied by Flexible Monodentate and Bidentate N,N'-bipyrdyl Ligands%A Novel Copper(Ⅱ) Coordination Polymer with Figure-of-eight-shaped Channels Occupied by Flexible Monodentate and Bidentate N,N'-bipyrdyl Ligands

    Institute of Scientific and Technical Information of China (English)

    PAN Peng-Bin; ZHANG Xin; YANG Jin-Xia; YIN Pei-Xiu; YAO Yuan-Gen

    2011-01-01

    A copper(Ⅱ) coordination polymer, [Cu3(HOA)2(bpp)4]n (1, HnOA = 3,3',4,4'- oxidiphthalic acid, bpp = 1,3-bis(4-pyridyl) propane), has been hydrothermally synthesized. The crystal structure is of monoclinic, space group P21/c with a = 11.544(3), b = 16.129(4), c = 21.181 (6) A, β = 98.848(5), V= 3897.0(2) A3, C84018N8H70Cu3, Mr = 1670.13, Z = 2, De = 1.423 g/cm^3, F(000) = 1722, μ = 0.887 mm^-1, R = 0.0878 and wR = 0.2583 for 8496 observed reflections (I 〉 2σ(I)). Single-crystal X-ray structural analysis reveals that 1 is a three-dimensional (3D) framework based on a two-dimensional (2D) mesomeric layer of alternating left- and fight-handed helical chains. The monodentate terminal and bidentate bridging bpp ligands in the same conformation are all encapsulated in the figure-of-eight-shaped channels, thus further stabilizing the whole three-dimensional framework.

  2. Polycations XX: New Monodentate Cationic Ligands and Their Coordination with Ruthenium for the Construction of Complexes Expressing Enhanced Interaction with DNA

    Directory of Open Access Journals (Sweden)

    Leslie Babukutty

    2012-01-01

    Full Text Available Prior investigations from this laboratory concerned with the preparation of new types of organic cations for a variety of biological and nonbiological applications have been extended to the preparation of cation-bearing ligands with nitrogen coordinating sites for use in complexation reactions with ruthenium cores. The syntheses of new cationic ligands as well as ruthenium complexes bearing them are reported here. The introduction of these new types of ligands is intended to provide to the complexes an enhanced ability to interact with DNA, and thereby to have the potential to be enhanced antitumor agents. Preliminary observations of their interactions with DNA are presented.

  3. Potentiometric and spectrometric study: Copper(II), nickel(II) and zinc(II) complexes with potentially tridentate and monodentate ligands

    Indian Academy of Sciences (India)

    R N Patel; Nripendra Singh; R P Shrivastava; K K Shukla; P K Singh

    2002-04-01

    Equilibrium and solution structural study of mixed-metal-mixed-ligand complexes of Cu(II), Ni(II) and Zn(II) with L-cysteine, L-threonine and imidazole are conducted in aqueous solution by potentiometry and spectrophotometry. Stability constants of the binary, ternary and quaternary complexes are determined at 25 ± 1 ° C and in = 0.1 M NaClO4. The results of these two methods are made selfconsistent, then rationalized assuming an equilibrium model including the species H3A, H2A, A, BH, B, M(OH), M(OH)2, M(A), MA(OH), M(B), M(A)(B), M2(A)2(B), M2(A)2(B-H), M1M2(A)2(B) and M1M2(A)2(B-H) (where the charges of the species have been ignored for the sake of simplicity) (A = L-cysteine, L-threonine, salicylglycine, salicylvaline and BH = imidazole). Evidence of the deprotonation of BH ligand is available at alkaline H. N1H deprotonation of the bidentate coordinated imidazole ligand in the binuclear species at H > 7.0 is evident from spectral measurements. Stability constants of binary M(A), M(B) and ternary M(A)(B), complexes follow the Irving-Williams order.

  4. Preparation and Investigation of Monodentate and Bridging Pyrazole Complexes

    Science.gov (United States)

    Evans, Wynne

    2004-01-01

    Complexes of pyrazole-derived ligands are very popular due to the ability of the pyrazolato anion to form bridged polymetallic compounds in which the metals are held close enough to react with small molecules or facilitate magnetic exchange. The preparation of monodentate pyrazole and 3,5-dimethylpyrazole (DMHpz) nickel species and the…

  5. Structure of a dinuclear cadmium complex with 2,2′-bipyridine, monodentate nitrate and 3-carboxy-6-methylpyridine-2-carboxylate ligands: intramolecular carbonyl(lone pair...π(ring and nitrate(π...π(ring interactions

    Directory of Open Access Journals (Sweden)

    Juan Granifo

    2015-08-01

    Full Text Available The centrosymmetric dinuclear complex bis(μ-3-carboxy-6-methylpyridine-2-carboxylato-κ3N,O2:O2;κ3O2:N,O2-bis[(2,2′-bipyridine-κ2N,N′(nitrato-κOcadmium] methanol monosolvate, [Cd2(C8H6NO42(NO32(C10H8N22]·CH3OH, was isolated as colourless crystals from the reaction of Cd(NO32·4H2O, 6-methylpyridine-2,3-dicarboxylic acid (mepydcH2 and 2,2′-bipyridine in methanol. The asymmetric unit consists of a CdII cation bound to a μ-κ3N,O2:O2-mepydcH− anion, an N,N′-bidentate 2,2′-bipyridine group and an O-monodentate nitrate anion, and is completed with a methanol solvent molecule at half-occupancy. The Cd complex unit is linked to its centrosymmetric image through a bridging mepydcH− carboxylate O atom to complete the dinuclear complex molecule. Despite a significant variation in the coordination angles, indicating a considerable departure from octahedral coordination geometry about the CdII atom, the Cd—O and Cd—N distances in this complex are surprisingly similar. The crystal structure consists of O—H...O hydrogen-bonded chains parallel to a, further bound by C—H...O contacts along b to form planar two-dimensional arrays parallel to (001. The juxtaposed planes form interstitial columnar voids that are filled by the methanol solvent molecules. These in turn interact with the complex molecules to further stabilize the structure. A search in the literature showed that complexes with the mepydcH− ligand are rare and complexes reported previously with this ligand do not adopt the μ-κ3 coordination mode found in the title compound.

  6. Synthesis, Spectroscopic, and Electrochemical Studies on Some New Copper(II Complexes Containing 2-{[(Z-Phenyl (Pyridine-2-yl Methylidene] Amino}Benzenethiol and Monodentate Ligands

    Directory of Open Access Journals (Sweden)

    S. P. Rawat

    2014-01-01

    Full Text Available Five new mononuclear copper(II complexes, namely, [Cu(L(ImH]·ClO41; [Cu(L(Me-ImH]·ClO42; [Cu(L(Et-ImH]·ClO43; [Cu(L(2-benz-ImH]·ClO44; [Cu(L(benz-ImH]·ClO45, where HL = 2-{[(Z-phenyl (pyridine-2-yl methylidene] amino} benzenethiol; ImH = Imidazole; Me-ImH = Methy-limidazole; Et-ImH = Ethyl-imidazole; 2-benz-ImH = 2-methyl-benzimidazole; benz-ImH = benz-imidazole, have been synthesized and characterized by various physicochemical and spectroscopic techniques. Magnetic moments, electronic spectra, and EPR spectra of the complexes suggested a square planar geometry around Cu(II ion. The synthesized HL ligand behaves as monobasic tridentate Schiff base bound with the metal ion in a tridentate manner, with N2S donor sites of the pyridine-N, azomethine-N, and benzenethiol-S atoms. The redox behaviour of the copper complexes has been studied by cyclic voltammetry. Superoxide dismutase activity of these complexes has been revealed to catalyse the dismutation of superoxide (O2- and IC50 values were evaluated and discussed.

  7. Oligo-nuclear silver thiocyanate complexes with monodentate tertiary phosphine ligands, including novel 'cubane' and 'step' tetramer forms of AgSCN : PR3 (1:1)4.

    Science.gov (United States)

    Bowmaker, Graham A; Di Nicola, Corrado; Effendy; Hanna, John V; Healy, Peter C; King, Scott P; Marchetti, Fabio; Pettinari, Claudio; Robinson, Ward T; Skelton, Brian W; Sobolev, Alexandre N; Tăbăcaru, Aurel; White, Allan H

    2013-01-07

    Adducts of a number of tertiary pnicogen ligands ER(3) (triphenyl-phosphine and -arsine (PPh(3),AsPh(3)), diphenyl,2-pyridylphosphine (PPh(2)py), tris(4-fluorophenyl)phosphine (P(C(6)H(4)-4F)(3)), tris(2-tolyl)phosphine (P(o-tol)(3)), tris(cyclohexyl)phosphine (PCy(3))), with silver(I) thiocyanate, AgSCN are structurally and spectroscopically characterized. The 1:3 AgSCN : ER(3) complexes structurally defined (for PPh(3),AsPh(3) (diversely solvated)) take the form [(R(3)E)(3)AgX], the thiocyanate X = NCS being N-bound, thus [(Ph(3)E)Ag(NCS)]. A 1:2 complex with PPh(2)py, takes the binuclear form [(pyPh(2)P)(2)Ag()Ag(PPh(2)py)(2)] with an eight-membered cyclic core. 1:1 complexes are defined with PPh(2)py, P(o-tol)(3) and PCy(3); binuclear forms [(R(3)P)Ag()Ag(PR(3))] are obtained with P(o-tol)(3) (two polymorphs), while novel isomeric tetranuclear forms, which may be envisaged as dimers of dimers, are obtained with PPh(2)py, and, as further polymorphs, with PCy(3); these latter may be considered as extensions of the 'cubane' and 'step' forms previously described for [(R(3)E)AgX](4) (X = halide) complexes. Solvent-assisted mechanochemical or solvent-assisted solid-state synthesis methods were employed in some cases, where complexes could not be obtained by conventional solution methods, or where such methods yielded a mixture of polymorphs unsuitable for solid-state spectroscopy. The wavenumbers of the ν(CN) bands in the IR spectra are in broad agreement with the empirical rule that distinguishes bridging from terminal bonding, but exceptions occur for compounds that have a double SCN bridged dimeric structure, and replacement of PPh(3) with PPh(2)py apparently causes a significant decrease in ν(CN) to well below the range expected for bridging SCN in these structures. (31)P CP MAS NMR spectra yield additional parameters that allow a correlation between the structures and spectra.

  8. Arsine

    Science.gov (United States)

    ... too. Seal the bag, and then seal that bag inside another plastic bag. Disposing of your clothing in this way will ... arrange for further disposal. Do not handle the plastic bags yourself. For more information about cleaning your body ...

  9. Reactions of arsine with hemoglobin

    Energy Technology Data Exchange (ETDEWEB)

    Hatlelid, K.M.; Brailsford, C.; Carter, D.E. [Univ. of Arizona, Tucson, AZ (United States)

    1996-02-09

    The mechanism of arsine (AsH{sub 3}) induced hemolysis was studied in vitro using isolated red blood cells (RBCs) from the rat or dog. AsH{sub 3}-induced hemolysis of dog red blood cells was completely blocked by carbon monoxide (CO) preincubation and was reduced by pure oxygen (O{sub 2}) compared to incubations in air. Since CO and O{sub 2} bind to heme and also reduced hemolysis, these results suggested a reaction between AsH{sub 3} and hemoglobin in the hemeligand binding pocket or with the heme iron. Further, sodium nitrite induction of methemoglobin (metHb) to 85% and 34% of total Hb in otherwise intact RBCs resulted in 56% and 16% decreases in hemolysis, respectively, after incubation for 4 h. This provided additional evidence for the involvement of hemoglobin in the AsH{sub 3}-induced hemolysis mechanism. Reactions between AsH{sub 3} and hemoglobin were studied in solutions of purified dog hemoglobin. Spectrophotometric studies of the reaction of AsH{sub 3} with various purified hemoglobin species revealed that AsH{sub 3} reacted with HbO{sub 2} to produce metHb and, eventually, degraded Hb characterized by gross precipitation of the protein. AsH{sub 3} did not alter the spectrum of deoxyHb and did not cause degradation of metHb in oxygen, but bound to and reduced metHb in the absence of oxygen. These data indicate that a reaction of AsH{sub 3} with oxygenated hemoglobin, HbO{sub 2}, may lead to hemolysis, but there are reactions between AsH{sub 3} and metHb that may not be directly involved in the hemolytic process. 17 refs., 6 figs.

  10. Monodentate phosphoramidites : A breakthrough in rhodium-catalysed asymmetric hydrogenation of olefins

    NARCIS (Netherlands)

    Berg, Michel van den; Minnaard, Adriaan J.; Haak, Robert M.; Leeman, Michel; Schudde, Ebe P.; Meetsma, Auke; de Vries, Andre H.M.; Maljaars, C. Elizabeth P.; Willans, Charlotte E.; Hyett, David; Boogers, Jeroen A.F.; Henderickx, Hubertus; Feringa, Ben L.

    2003-01-01

    Monodentate phosphoramidites based on BINOL or substituted BINOL are excellent ligands for the rhodium-catalysed asymmetric hydrogenation of olefins. Very high enantioselectivities were obtained with MonoPhos (7a) the simplest member of this class, a ligand that is prepared in a single step from BIN

  11. Asymmetric hydrogenation of quinolines catalyzed by iridium complexes of monodentate BINOL-derived phosphoramidites

    NARCIS (Netherlands)

    Mrsic, Natasa; Lefort, Laurent; Boogers, Jeroen A. F.; Minnaard, Adriaan J.; Feringa, Ben L.; de Vries, Johannes G.; Mršić, Nataša

    The monodentate BINOL-derived phosphoramidite PipPhos is used as ligand for the iridium-catalyzed asymmetric hydrogenation of 2- and 2,6-substituted quinolines. If tri-ortho-tolylphosphine and/or chloride salts are used as additives enantioselectivities are strongly enhanced up to 89%. NMR indicates

  12. Acute arsine intoxication as a consequence of metal burnishing operations.

    Science.gov (United States)

    Romeo, L; Apostoli, P; Kovacic, M; Martini, S; Brugnone, F

    1997-09-01

    The report concerns a 30-year-old factory worker, employed in a small galvanizing plant for over ten years in the burnishing, copper- and nickel-plating of small metal articles for the shoe industry. Acute arsine poisoning was attributed to the use of a dilute solution of CuSO4 (3%), HCl (32%), and As2O3 (2%) for burnishing metal (Fe-Zn) shoelace eyelet holes, in the absence of local exhaust ventilation and with no respiratory protection. Arsine caused severe intravascular hemolysis with a rapid drop in hematocrit and hemoglobin levels. Other body organs were involved as a result of the hypoxic effect of anemia and hemolysis, or as a direct toxic effect of the arsine itself. Our experience confirms that exchange transfusion is capable of rapidly arresting the adverse effects of arsine. The importance of preventive measures and worker information to avoid acute arsine poisoning is emphasized.

  13. Field fluxes and speciation of arsines emanating from soils.

    Science.gov (United States)

    Mestrot, Adrien; Feldmann, Joerg; Krupp, Eva M; Hossain, Mahmud S; Roman-Ross, Gabriela; Meharg, Andrew A

    2011-03-01

    The biogeochemical cycle of arsenic (As) has been extensively studied over the past decades because As is an environmentally ubiquitous, nonthreshold carcinogen, which is often elevated in drinking water and food. It has been known for over a century that micro-organisms can volatilize inorganic As salts to arsines (arsine AsH(3), mono-, di-, and trimethylarsines, MeAsH(2), Me(2)AsH, and TMAs, respectively), but this part of the As cycle, with the exception of geothermal environs, has been almost entirely neglected because of a lack of suited field measurement approaches. Here, a validated, robust, and low-level field-deployable method employing arsine chemotrapping was used to quantify and qualify arsines emanating from soil surfaces in the field. Up to 240 mg/ha/y arsines was released from low-level polluted paddy soils (11.3 ± 0.9 mg/kg As), primarily as TMAs, whereas arsine flux below method detection limit was measured from a highly contaminated mine spoil (1359 ± 212 mg/kg As), indicating that soil chemistry is vital in understanding this phenomenon. In microcosm studies, we could show that under reducing conditions, induced by organic matter (OM) amendment, a range of soils varied in their properties, from natural upland peats to highly impacted mine-spoils, could all volatilize arsines. Volatilization rates from 0.5 to 70 μg/kg/y were measured, and AsH(3), MeAsH(2), Me(2)AsH, and TMAs were all identified. Addition of methylated oxidated pentavalent As, namely monomethylarsonic acid (MMAA) and dimethylarsinic acid (DMAA), to soil resulted in elevated yearly rates of volatilization with up to 3.5% of the total As volatilized, suggesting that the initial conversion of inorganic As to MMAA limits the rate of arsine and methylarsines production by soils. The nature of OM amendment altered volatilization quantitatively and qualitatively, and total arsines release from soil showed correlation between the quantity of As and the concentration of dissolved organic

  14. Mechanism for the formation of substituted manganese(V) cyanidonitrido complexes: crystallographic and kinetic study of the substitution reactions of trans-[MnN(H2O)(CN)4]2- with monodentate pyridine and bidentate pyridine-carboxylate ligands.

    Science.gov (United States)

    van der Westhuizen, Hendrik J; Meijboom, Reinout; Schutte, Marietjie; Roodt, Andreas

    2010-10-18

    Dissolution of [(CH(3))N](2)Na[MnN(CN)(5)]·H(2)O in water results in the rapid dissociation of the trans-CN(-) ligand to form trans-[MnN(H(2)O)(CN)(4)](2-)(aq), which reacts with monodentate pyridine ligands such as 3-methyl and 4-methyl pyridine to form the corresponding mono-substituted complexes, of which the molecular structures obtained from X-ray crystallography, trans-[MnN(3-pic)(CN)(4)](2-) and trans-[MnN(4-pic)(CN)(4)](2-), are reported. [MnN(H(2)O)(CN)(4)](2-)(aq) also reacts with bidentate nucleophiles such as pyridine-2-carboxylate (pico) and quinoline-2-carboxylate (quino), yielding the corresponding [MnN(η(2)-pico)(CN)(3)](2-) and [MnN(η(2)-quino)(CN)(3)](2-) complexes as determined by X-ray crystallography. The formation kinetics of pyridine-2-carboxylate and three different pyridine-2,x-dicarboxylate ligands (x = 3, 4, 5) are reported, and two consecutive reaction steps are proposed, defined as the formation of the [MnN(η(1)-pico)(CN)(4)](3-) and [MnN(η(2)-pico)(CN)(3)](3-) complexes, respectively. Only the second steps could be spectrophotometrically observed and kinetically investigated. The first reaction is attributed to the rapid aqua substitution of [MnN(H(2)O)(CN)(4)](2-), thermodynamically unfavored and too fast to observe by conventional rapid third generation stopped-flow techniques. The second, slower reaction is attributed to cyanido substitution, with overall formation rate constants (25 °C; k(1)'; M(-1) s(-1)) and corresponding activation parameters (ΔH(k1')(double dagger), kJ mol(-1), ΔS(k1')(double dagger), J K(-1) mol(-1)) for the following entering bidentate nucleophiles: pyridine-2-carboxylate: (1.15 ± 0.04) × 10(-3), 102 ± 1, and 48 ± 3; pyridine-2,3-dicarboxylate: (1.1 ± 0.1) × 10(-3), 93 ± 2, and 20 ± 4; pyridine-2,4-dicarboxylate (8.5 ± 0.5) × 10(-4), 123 ± 5, and 115 ± 14; pyridine-2,5-dicarboxylate: (1.08 ± 0.04) × 10(-3), 106 ± 1, and 60 ± 2. A dissociative activation for the cyanido substitution

  15. Continuous Arsine Detection Using a Peltier-Effect Cryogenic Trap To Selectively Trap Methylated Arsines.

    Science.gov (United States)

    Chen, Guoying; Lai, Bunhong; Mao, Xuefei; Chen, Tuanwei; Chen, Miaomiao

    2017-09-05

    Hydride generation (HG) is an effective technique that eliminates interfering matrix species and enables hydride separation. Arsenic speciation analysis can be fulfilled by cryogenic trapping (CT) based on boiling points of resulting arsines using liquid nitrogen (LN2) as a coolant. In this work, LN2 was replaced by the thermoelectric effect using a cryogenic trap that consisted of a polytetrafluoroethylene (PTFE) body sandwiched by two Peltier modules. After the trap was precooled, the arsines flew along a zigzag channel in the body and reached a sorbent bed of 0.2 g of 15% OV-3 on Chromosorb W-AW-DMCS imbedded near the exit of the trap. CH3AsH2 and (CH3)2AsH were trapped, while AsH3, that passed the trap unaffected, was detected by atomic fluorescence spectrometry. Continuous operation led to enhanced throughput. For inorganic As, the limit of detection (LOD) was 1.1 ng/g and recovery was 101.0 ± 1.1%. Monomethylarsonic acid and dimethylarsinic acid did not interfere with 0.2 ± 1.2% and -0.3 ± 0.5% recoveries, respectively.

  16. The role of arsine in the deactivation of methanol synthesis catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Quinn, R.; Mebrahtu, T.; Dahl, T.A.; Lucrezi, F.A.; Toseland, B.A. [Air Products and Chemicals Inc., Adsorption Technology Center, 7201 Hamilton Boulevard, Allentown, PA 18195-1501 (United States)

    2004-06-18

    The liquid phase methanol (LPMEOH) process is successfully producing methanol from coal-derived synthesis gas on an industrial scale. This process uses a standard copper, zinc oxide, and alumina catalyst suspended in an inert mineral oil in a slurry bubble column reactor. An arsenic-containing species, most reasonably arsine, was found in the feed to the LPMEOH commercial demonstration facility located at Eastman Chemical Company's chemicals-from-coal complex in Kingsport, TN. Laboratory testing showed that arsine is, in fact, a powerful methanol synthesis catalyst poison. At levels as low as 150ppbv, arsine results in a rapid deactivation of the catalyst. Removal of arsine results in a deactivation rate consistent with a clean synthesis gas feed; that is, arsine poisoning stops when it is removed from the feed. We infer that arsine reacts irreversibly with the catalyst under the methanol synthesis conditions. X-ray absorption spectroscopy (XAS) of arsenic-containing used catalyst indicated the presence of zero-valent arsenic in an intermetallic surface phase that is structurally related to Domeykite (Cu{sub 3}As). Experimental evidence, thermodynamics, and literature relating to other metal-arsine chemistry were consistent with dissociative adsorption of arsine on the copper surface to form gaseous H{sub 2} and Cu{sub 3}As. To deal with arsine poisoning, we have developed adsorption technology that can remove arsine to levels low enough that catalyst performance is unaffected.

  17. Arsine and its fluoro, chloro derivatives: a computational thermochemical study

    Science.gov (United States)

    Bagchi, Sabyasachi; Mondal, Bhaskar; Ghosh, Deepanwita; Das, Abhijit K.

    2010-01-01

    The structures, vibrational frequencies, enthalpies of formation and dissociation energies of arsine, arsenic hydrides and their fluoro, chloro derivatives have been studied using density functional B3LYP/cc-pVDZ, ab-initio MP2/cc-pVDZ and composite CBS-QB3 and CBS-Q methods. Computed standard enthalpies of formation at 298 K by atomisation scheme are compared with reported values. Bond dissociation energies at 0 K are calculated for all possible thermal dissociation of the molecular species in gas phase, from which the energetically most favourable dissociation pathways are predicted. The calculated enthalpies of formation and bond dissociation energies are correlated with the nature of bonding in arsine and its fluoro, chloro derivatives. Energy barriers at 0 K are calculated and transition states are located for the molecular fragment elimination of the thermal dissociation reactions.

  18. Suspected arsine poisoning during the restoration of a large cyclorama painting.

    Science.gov (United States)

    Williams, P L; Spain, W H; Rubenstein, M

    1981-12-01

    Arsine poisoning is a well-recognized phenomenon generally associated with the smelting and refining of metals. However, acute episodes of arsine poisoning do occur in environments unrelated to metal processing and often go unrecognized. The incident described herein, which deals with artists working on the restoration of a famous painting, illustrates that arsine gas may evolve in any situation where nascent hydrogen comes in contact with small amounts of arsenic.

  19. Tetracarboxylatoplatinum(IV) complexes featuring monodentate leaving groups - A rational approach toward exploiting the platinum(IV) prodrug strategy.

    Science.gov (United States)

    Höfer, Doris; Varbanov, Hristo P; Legin, Anton; Jakupec, Michael A; Roller, Alexander; Galanski, Markus; Keppler, Bernhard K

    2015-12-01

    A series of novel symmetrically and unsymmetrically coordinated platinum(IV) complexes with monodentate carboxylato ligands was synthesized. The compounds exhibit a general coordination sphere of [Pt(en)(OCOR)2(OCOR')(OCOR″)], where the carboxylato ligands are represented by acetato and succinic acid monoester ligands. Dicarboxylatoplatinum(II) complexes were synthesized and oxidized symmetrically or unsymmetrically to obtain platinum(IV) complexes, which were subsequently carboxylated with noncyclic anhydrides. The compounds were investigated in detail by elemental analysis, mass spectrometry, infrared and multinuclear ((1)H, (13)C, (15)N, (195)Pt) NMR spectroscopy as well as by X-ray diffraction in some cases. The reduction behavior was followed by NMR spectroscopy, while stability and lipophilicity were examined by analytical reversed phase HPLC measurements. Cytotoxic properties were studied in three human cancer cell lines derived from cisplatin sensitive ovarian teratocarcinoma (CH1/PA-1), cisplatin insensitive colon carcinoma (SW480) and non-small cell lung cancer (A549). Thereby, the most lipophilic (yet water soluble) platinum(IV) complexes showed promising IC50 values in the low micromolar and even nanomolar range, demonstrating the significant advantage of using equatorially coordinated monodentate carboxylato ligands. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Quantitative and qualitative trapping of arsines deployed to assess loss of volatile arsenic from paddy soil.

    Science.gov (United States)

    Mestrot, Adrien; Uroic, M Kalle; Plantevin, Thomas; Islam, Md Rafiqul; Krupp, Eva M; Feldmann, Jörg; Meharg, Andrew A

    2009-11-01

    Arsenic volatilization in the environment is thought to be an important pathway for transfer from terrestrial pools to the atmosphere. However, this phenomenon is not well characterized due to inherent sampling issues in trapping, quantifying and qualifying these arsine gases; including arsine (AsH(3)), monomethyl arsine (MeAsH(2)), dimethyl arsine (Me(2)AsH) and trimethyl arsine (TMAs). To quantify and qualify arsines in air we developed a novel technique based on silver nitrate impregnated silica gel filled tubes. The method was characterized by measuring the recovery of trapped arsines after elution of this chemo-trap with hot boiling diluted nitric acid. Results from three separate experiments, measured by ICP-MS, showed that the method is reproducible and quantitative. Arsine species recovery ranged from 80.1 to 95.6%, with limit of detection as low as 3.8 ng per chemo-trap tube. Moreover, HPLC-ICP-MS analysis of hot boiling water eluted traps showed that the corresponding oxy ions of the arsines were formed with the As-C bonds of the molecule intact, hence, allowing qualification of trapped arsine species. A microcosm study examining volatile arsenic evolution from field contaminated Bangladeshi paddy soils (24.2 mg/kg arsenic) was used to show the application of silver nitrate chemo-trapping approach. Traps were placed on the inlet and the outlet of microcosms containing the soils that were either (cattle derived) manured or not, or flooded or not, in a factorial design. The headspace was purged with air at a flow rate of 12 mL/min. Results showed that as much as 320 ng of arsenic (0.014% of total soil content) could be emitted in a 3 week period for manured and flooded soils and that TMAs was the dominant species evolved, with lesser quantities of Me(2)AsH. No volatile arsenic evolution was observed for nonmanured treatments, and arsine release from the nonflooded, manured treatment was much less than the flooded treatment.

  1. Arsine oxidation with heteropoly acid in the presence of halide ions

    Energy Technology Data Exchange (ETDEWEB)

    Dorfman, Ya.A.; Aleshkova, M.M.; Doroshkevich, D.M.; Kel' man, I.V. (AN Kazakhskoj SSR, Alma-Ata. Inst. Organicheskogo Kataliza i Ehlektrokhimii)

    1984-12-01

    Kinetics and mechanism of arsine oxidation by phosphomolybdovanadium heteropoly acid are studied in the presense of halide ions as catalysts. It is established that intrasphere arsine oxidation in an intermediate V(5) complex with AsH/sub 3/ and halide-ion is a limiting stage of the proposed mechanism. The quantum-chemical calculation of the electronic structure of intermediate complexes, which supports the above mechanism is carried out. The method of theoretical estimation of the activation energy is proposed.

  2. Bidentates versus monodentates in asymmetric hydrogenation catalysis: synergic effects on rate and allosteric effects on enantioselectivity.

    Science.gov (United States)

    Norman, David W; Carraz, Charles A; Hyett, David J; Pringle, Paul G; Sweeney, Joseph B; Orpen, A Guy; Phetmung, Hirrahataya; Wingad, Richard L

    2008-05-28

    C 1-Symmetric phosphino/phosphonite ligands are prepared by the reactions of Ph 2P(CH 2) 2P(NMe 2) 2 with ( S)-1,1'-bi-2-naphthol (to give L A ) or ( S)-10,10'-bi-9-phenanthrol (to give L B ). Racemic 10,10'-bi-9-phenanthrol is synthesized in three steps from phenanthrene in 44% overall yield. The complexes [PdCl 2( L A,B )] ( 1a, b), [PtCl 2( L A,B )] ( 2a, b), [Rh(cod)( L A,B )]BF 4 ( 3a, b) and [Rh( L A,B ) 2]BF 4 ( 4a, b) are reported and the crystal structure of 1a has been determined. A (31)P NMR study shows that M, a 1:1 mixture of the monodentates, PMePh 2 and methyl monophosphonite L 1a (based on ( S)-1,1 '-bi-2-naphthol), reacts with 1 equiv of [Rh(cod) 2]BF 4 to give the heteroligand complex [Rh(cod)(PMePh 2)( L 1a )]BF 4 ( 5) and homoligand complexes [Rh(cod)(PMePh 2) 2]BF 4 ( 6) and [Rh(cod)( L 1a ) 2]BF 4 ( 7) in the ratio 2:1:1. The same mixture of 5- 7 is obtained upon mixing the isolated homoligand complexes 6 and 7 although the equilibrium is only established rapidly in the presence of an excess of PMePh 2. The predominant species 5 is a monodentate ligand complex analogue of the chelate 3a. When the mixture of 5- 7 is exposed to 5 atm H 2 for 1 h (the conditions used for catalyst preactivation in the asymmetric hydrogenation studies), the products are identified as the solvento species [Rh(PMePh 2)( L 1a )(S) 2]BF 4 ( 5'), [Rh(S) 2(PMePh 2) 2]BF 4 ( 6') and [Rh(S) 2( L 1a ) 2]BF 4 ( 7') and are formed in the same 2:1:1 ratio. The reaction of M with 0.5 equiv of [Rh(cod) 2]BF 4 gives exclusively the heteroligand complex cis-[Rh(PMePh 2) 2( L 1a ) 2]BF 4 ( 8), an analogue of 4a. The asymmetric hydrogenation of dehydroamino acid derivatives catalyzed by 3a, b is reported, and the enantioselectivities are compared with those obtained with (a) chelate catalysts derived from analogous diphosphonite ligands L 2a and L 2b , (b) catalysts based on methyl monophosphonites L 1a and L 1b , and (c) catalysts derived from mixture M. For the cinnamate and

  3. De acute arsine-intoxicatie. Richtlijnen voor opvang door EHBO'ers, ambulance-personeel en (bedrijfs)arts van slachtoffers van expositie aan arsine

    NARCIS (Netherlands)

    Remmert HP; Cremers PMA

    1987-01-01

    De gevaren verbonden aan de expositie aan arsine maken het wenselijk dat een protocol beschikbaar is waarbij minimaal de hoofdlijnen zijn aangegeven hoe bij dergelijke ongevallen te handelen. Dit document bevat een voorstel daartoe, waarin vooral aandacht is besteed aan de medische aspecten bij

  4. De acute arsine-intoxicatie. Richtlijnen voor opvang door EHBO'ers, ambulance-personeel en (bedrijfs)arts van slachtoffers van expositie aan arsine

    NARCIS (Netherlands)

    Remmert HP; Cremers PMA

    1987-01-01

    De gevaren verbonden aan de expositie aan arsine maken het wenselijk dat een protocol beschikbaar is waarbij minimaal de hoofdlijnen zijn aangegeven hoe bij dergelijke ongevallen te handelen. Dit document bevat een voorstel daartoe, waarin vooral aandacht is besteed aan de medische aspecten bij

  5. Structure of a dinuclear cadmium complex with 2,2'-bi-pyridine, monodentate nitrate and 3-carb-oxy-6-methyl-pyridine-2-carboxyl-ate ligands: intra-molecular carbon-yl(lone pair)⋯π(ring) and nitrate(π)⋯π(ring) inter-actions.

    Science.gov (United States)

    Granifo, Juan; Suarez, Sebastián; Baggio, Ricardo

    2015-08-01

    The centrosymmetric dinuclear complex bis-(μ-3-carb-oxy-6-methyl-pyridine-2-carboxyl-ato)-κ(3) N,O (2):O (2);κ(3) O (2):N,O (2)-bis-[(2,2'-bi-pyridine-κ(2) N,N')(nitrato-κO)cadmium] methanol monosolvate, [Cd2(C8H6NO4)2(NO3)2(C10H8N2)2]·CH3OH, was isolated as colourless crystals from the reaction of Cd(NO3)2·4H2O, 6-methyl-pyridine-2,3-di-carb-oxy-lic acid (mepydcH2) and 2,2'-bi-pyridine in methanol. The asymmetric unit consists of a Cd(II) cation bound to a μ-κ(3) N,O (2):O (2)-mepydcH(-) anion, an N,N'-bidentate 2,2'-bi-pyridine group and an O-mono-dentate nitrate anion, and is completed with a methanol solvent mol-ecule at half-occupancy. The Cd complex unit is linked to its centrosymmetric image through a bridging mepydcH(-) carboxyl-ate O atom to complete the dinuclear complex mol-ecule. Despite a significant variation in the coordination angles, indicating a considerable departure from octa-hedral coordination geometry about the Cd(II) atom, the Cd-O and Cd-N distances in this complex are surprisingly similar. The crystal structure consists of O-H⋯O hydrogen-bonded chains parallel to a, further bound by C-H⋯O contacts along b to form planar two-dimensional arrays parallel to (001). The juxtaposed planes form inter-stitial columnar voids that are filled by the methanol solvent mol-ecules. These in turn inter-act with the complex mol-ecules to further stabilize the structure. A search in the literature showed that complexes with the mepydcH(-) ligand are rare and complexes reported previously with this ligand do not adopt the μ-κ(3) coordination mode found in the title compound.

  6. Catalytic enantioselective addition of organometallic reagents to N-formylimines using monodentate phosphoramidite ligands

    NARCIS (Netherlands)

    Pizzuti, Maria Gabriella; Minnaard, Adriaan J.; Feringa, Ben L.

    2008-01-01

    [GRAPHICS] The asymmetric synthesis of protected amines via the copper/phosphoramidite-catalyzed addition of organozine and organoaluminum reagents to N-acylimines, generated in situ from aromatic and aliphatic alpha-amidosulfones, is reported. High yields of optically active N-formyl-protected amin

  7. Catalytic Enantioselective Addition of Organometallic Reagents to N-Formylimines Using Monodentate Phosphoramidite Ligands

    NARCIS (Netherlands)

    Pizzuti, Maria Gabriella; Minnaard, Adriaan J.; Feringa, Bernard

    2008-01-01

    The asymmetric synthesis of protected amines via the copper/phosphoramidite-catalyzed addition of organozinc and organoaluminum reagents to N-acylimines, generated in situ from aromatic and aliphatic α-amidosulfones, is reported. High yields of optically active N-formyl-protected amines and enantios

  8. Fast Palladium Catalyzed Arylation of Alkenes Using Bulky Monodentate Phosphorus Ligands

    NARCIS (Netherlands)

    Strijdonck, Gino P.F. van; Boele, Maarten D.K.; Kamer, Paul C.J.; Vries, Johannes G. de; Leeuwen, Piet W.N.M. van

    1999-01-01

    Complex 1b shows an unprecedented high activity in the Heck reaction. Kinetic studies show that in this system not the oxidative addition but the alkene coordination/migratory insertion is the rate determining step.

  9. Silver and gold nanocluster catalyzed reduction of methylene blue by arsine in micellar medium

    Indian Academy of Sciences (India)

    Subrata Kundu; Sujit Kumar Ghosh; Madhuri Mandal; Tarasankar Pal

    2002-11-01

    Arsenic can be determined in parts-per-million (ppm) level by absorbance measurement. This method is based on the quantitative colour bleaching of the dye, methylene blue by arsine catalyzed by nanoparticles in micellar medium. The arsine has been generated in situ from sodium arsenate by NaBH4 reduction. The absorbance measurement was carried out at the max of the dye at 660 nm. The calibration graph set-up for three linear dynamic ranges (LDR) are 0–8.63 ppm, 0–1.11 ppm and 0–0.11 ppm and limit of detections (LODs) are 1.3, 0.53 and 0.03 ppm, respectively. This method is simple, sensitive and easy to carry out. It is free from phosphate and silicate interference and applicable to real sample analysis.

  10. Mg(II)-induced second-harmonic generation based on bis-monodentate coordination mode of thiobarbiturate.

    Science.gov (United States)

    Gong, Yun; Hao, Zhi; Li, JingHua; Wu, Tao; Lin, JianHua

    2013-05-14

    Utilizing a SHG inactive ligand, 2-thiobarbituric acid (H3L), three metal complexes formulated as M(H2L)2(H2O)2·2DMF (M = Mg 1 and Ni 2) and Co(H2L)2(H2O)2 (3) were synthesized and structurally characterized by single-crystal X-ray diffractions. Complexes 1 and 2 exhibit a similar uninodal 3D acentric diamondoid framework. Complex 1 displays SHG response using 1064 nm radiation, whereas complex 2 is SHG inactive under the same condition. Complex 3 is also SHG inactive, which exhibits a centro-symmetrical chain-like structure built from Co(II) ions and double strands of H2L(-)-bridge with the inversion center occupied by the metal(II) ion. In the three complexes, the negative charge of H2L(-) ligand is delocalized over the O=C-CH-C=O group and H2L(-) can be considered as a β-diketo derivative. H2L(-) shows a bis-monodentate coordination fashion and acts as a u2-bridge in the three complexes, which is different from the classical chelating fashion of β-diketo ligand. In complexes 1 and 2, the two β-diketo oxygen atoms of H2L(-) are coordinated to two metal centers. Whereas in complex 3, H2L(-) ligand links two Co(II) centers via one oxygen and one sulphur atoms. The three complexes exhibit different UV-vis absorption, photoluminescence properties and thermal stabilities.

  11. Bis(ortho)-Chelated Bis(phosphanyl)aryl Ruthenium(II).Complexes Containing an h1 -P-Monodentate or m -BridgingP,h1-P' Bonded R—PCHP Arene Ligand, 1-R-3,5(CH2PPh2)2C2H2 [R= H, Br, or, Si(n-CH2CH2C2F17)3]—Cyclometalation Reaction Intermediates and Potential Catalysts for Use in Fluorinated Biphasic Systems

    NARCIS (Netherlands)

    Koten, G. van; Dani, P.; Richter, B.; Klink, G.P.M. van

    2001-01-01

    Mono- and binuclear ruthenium(II) complexes containing ligands derived from the meta-bis(phosphanyl)arene ligand 1-R-3,5-(CH2PPh2)2C6H3 [R-PCHP: R = H (5), Br (3), or Si(n-CH2CH2C8F17)3 (4)] have been synthesized and fully characterized. On reaction of equimolar amounts of the ruthenium starting mat

  12. Speciation analysis of arsenic compounds in the serum and urine of a patient with acute arsine poisoning

    Directory of Open Access Journals (Sweden)

    Yamanaka K.

    2013-04-01

    Full Text Available Arsine is one of the most potent hemolytic agents. It is important to clarify arsine metabolism as well as its chemical interactions with biological components. The aim of the present study was to clarify arsine metabolism by arsenic speciation analysis in serum and urine from an acute poisoning patient with hematuria, anemia, and renal and liver dysfunction. Speciation analysis of arsenics in serum and urine was performed using HPLC-ICP-MS. The total arsenic (T-As concentration in serum was 244.8 μg/l at admission and 97.1 μg/l at discharge. In the speciation analysis, four kinds of As compounds derived from arsine metabolism were detected in serum and urine. The concentration of arsenite (AsIII, arsenate (AsV, monomethylarsonic acid (MMA, and dimethylarsinic acid (DMA in serum at admission were 45.8, 5.2, 17.9 and 9.3 μg/l, respectively. The concentrations of AsIII, AsV, and MMA decreased with biological half time (BHT of 30.1, 43.0, and 96.3 h, respectively. Only DMA was increased at discharge. The urinary AsIII, AsV, MMA and DMA concentrations were 223.0, 12.1, 317.5 and 1053.5 μg/l at discharge, and decreased with BHT of 15.1, 20.8, 14.7, and 16.0 d, respectively. The results indicate that arsine was quickly metabolized to AsIII and subsequently up to DMA, with the result that the toxic effects of inorganic arsenic were added to those of arsine toxicity.

  13. The Effect of Oxidation on the Surface Chemistry of Sulfur-Containing Carbons and their Arsine Adsorption Capacity

    Science.gov (United States)

    2010-01-01

    hydrogen sulfide . Carbon 2004;42(3):469–76. Fig. 6 – Water adsorption isotherms of the samples studied. 1786 C A R B O N 4 8 ( 2 0 1 0 ) 1 7 7 9 –1 7 8...that oxygen- and sulfur-containing groups participate in arsine oxida- tion to arsenic tri- and pentoxide and/or in the formation of arsenic sulfides ...technological difficulties, arsine is also a powerful toxin susceptible to oxidation with a strong exothermic effect. Of all the methods to separate

  14. Cyclopentadienyl Rhenium (Technetium) Tricarbonyl Complexes Integrated in Estrogen Receptor Ligands for ER+ Tumor Imaging

    Science.gov (United States)

    2006-10-01

    Oxidation to the N-oxide 38 with peroxy acid, with subsequent rearrangement provides the alcohol 39. Treatment of 39 with triflic anhydride in...anionic monodentate ligand is bromide for the pyridyl-imine rhenium tricarbonyl bromide (PIRB VI) system. A nomenclature of PIRB ligands is based

  15. Solid-Phase Parallel Synthesis of Phosphite Ligands

    NARCIS (Netherlands)

    Swennenhuis, Bert H.G.; Chen, Ruifang; Leeuwen, Piet W.N.M. van; Vries, Johannes G. de; Kamer, Paul C.J.

    2008-01-01

    Various routes for the synthesis of polymer-bound phosphites and phosphoramidites have been investigated. In the presence of a suitable activator the supported phosphoramidites react cleanly with alcohols to give the corresponding monodentate phosphite ligands in solution. We have applied this novel

  16. Stibine/arsine monitoring during EV operation: summary report on preliminary tests at ANL and at LILCO

    Energy Technology Data Exchange (ETDEWEB)

    Loutfy, R.O.; Graczyk, D.G.; Varma, R.; Hayes, E.R.; Williams, F.L.; Yao, N.P.

    1981-02-01

    A series of tests was performed to monitor the evolution and dispersal of stibine and arsine from the lead-acid propulsion batteries in three different Electra-Van Model 600 vehicles operated by Argonne National Laboratory (ANL) and by the Long Island Lighting Company (LILCO). Ambient air was sampled at several locations inside the vehicles and in the garages where testing was done during charge, equalization charge, and on-the-road discharge operations. In addition, direct sampling of cell off-gases was performed with the ANL van. Interpretation of the individual test results was carried out in the context of vehicle characteristics, sampling protocol, and operating conditions. The test results demonstrated that under the test conditions only small concentrations of stibine and arsine accumulated in occupiable work areas. Measured concentrations in the vehicles and in the garages never exceeded 25% of the Threshold Limit Value-Time Weighted Average (TLV-TWA) standards. A threshold voltage for hydride production, at about 2.45 V per cell, was reflected in the results of the experiments performed during charging of the batteries. Hydride evolution rates were lower during equalization charge than during the overcharge portion of a charge cycle when the on-board charger was used in a normal operating mode. A delayed release of the metal hydrides from the battery cells was observed during on-the-road operation of the vehicles. The implications of these observations for electric vehicle (EV) operation are discussed. An engineering analysis of the generation and dispersal of the metal hydrides is presented, and equations are derived for estimating minimum ventilation requirements for the EV battery compartment and for garages housing EV operations. Recommendations are made regarding safe handling procedures for battery off-gases, procedures for conducting stibine/arsine monitoring tests and future work.

  17. Influence of Axial and Peripheral Ligands on the Electronic Structure of Titanium Phthalocyanines

    NARCIS (Netherlands)

    Pickup, David F.; Zegkinoglou, Ioannis; Ballesteros, Beatriz; Ganivet, Carolina R.; Garcia-Lastra, J. M.; Cook, Peter L.; Johnson, Phillip S.; Rogero, Celia; de Groot, Frank; Rubio, Angel; de la Torre, Gema; Enrique Ortega, J.; Himpsel, F. J.

    2013-01-01

    To discover how molecular changes affect the electronic structure of dye molecules for solar cells, we have investigated four titanium phthalocyanines customized by axial and peripheral ligands (monodentate oxo versus bidentate catechol and tert-butyl versus tert-butylphenoxy, respectively). X-ray a

  18. Ligand-guided pathway selection in nickel-catalyzed couplings of enals and alkynes.

    Science.gov (United States)

    Li, Wei; Montgomery, John

    2012-01-28

    Nickel-catalyzed couplings of enals and alkynes utilizing triethylborane as the reducing agent illustrate a significant dependence on ligand structure. Simple variation of monodentate phosphines allows selective access to alkylative couplings or reductive cycloadditions, while further variation of reaction conditions provides clean access to reductive couplings and redox-neutral couplings.

  19. Influence of axial and peripheral ligands on the electronic structure of titanium phthalocyanines

    DEFF Research Database (Denmark)

    Pickup, David F.; García Lastra, Juan Maria; Rogero, Celia

    2013-01-01

    To discover how molecular changes affect the electronic structure of dye molecules for solar cells, we have investigated four titanium phthalocyanines customized by axial and peripheral ligands (monodentate oxo versus bidentate catechol and tert-butyl versus tert-butylphenoxy, respectively). X-ra...

  20. Tuning of gate adsorption: modification of a flexible metal-organic framework by secondary organic ligands.

    Science.gov (United States)

    Kondo, Atsushi; Fujii, Takuro; Maeda, Kazuyuki

    2014-06-14

    For realizing selective adsorption of targeted molecules, a flexible metal-organic framework (MOF) was modified with monodentate secondary ligands. Although the modified MOF retains CO2 adsorptivities with a vertical adsorption uptake, the material also shows gate adsorptivities of a specific gas molecule that the pristine MOF does not adsorb.

  1. Atmospheric Hydrogenation of Esters Catalyzed by PNP-Ruthenium Complexes with an N-Heterocyclic Carbene Ligand.

    Science.gov (United States)

    Ogata, Osamu; Nakayama, Yuji; Nara, Hideki; Fujiwhara, Mitsuhiko; Kayaki, Yoshihito

    2016-08-01

    New pincer ruthenium complexes bearing a monodentate N-heterocyclic carbene ligand were synthesized and demonstrated as powerful hydrogenation catalysts. With an atmospheric pressure of hydrogen gas, aromatic, heteroaromatic, and aliphatic esters as well as lactones were converted into the corresponding alcohols at 50 °C. This reaction protocol offers reliable access to alcohols using an easy operational setup.

  2. Study of the spectroscopic characteristics of methyl (ligand) cobaloximes and their antibacterial activity

    Indian Academy of Sciences (India)

    N Navaneetha; P A Nagarjun; S Satyanarayana

    2007-01-01

    Spectroscopic characterization (IR, NMR and electronic spectra) of methyl (ligand) cobaloxime was done, where ligand = pyrazole, dimethyl pyrazole, alanine and alanine methyl ester. The frequency changes in the IR spectra and shifts in the NMR were explained on the basis of basicity of the ligand, steric hindrance, HSAB principle and - back-bonding from metal to ligand. Alanine and alanine methyl ester form more stable complexes than pyrazole and dimethyl pyrazole. Based on their IR and 1H NMR spectra it is inferred that pyrazole and dimethylpyrazole bind to Co (III) via N-2 ring nitrogen, i.e. monodentate coordination.

  3. Investigating silver coordination to mixed chalcogen ligands.

    Science.gov (United States)

    Knight, Fergus R; Randall, Rebecca A M; Wakefield, Lucy; Slawin, Alexandra M Z; Woollins, J Derek

    2012-11-08

    Six silver(I) coordination complexes have been prepared and structurally characterised. Mixed chalcogen-donor acenaphthene ligands L1-L3 [Acenap(EPh)(E'Ph)] (Acenap = acenaphthene-5,6-diyl; E/E' = S, Se, Te) were independently treated with silver(I) salts (AgBF₄/AgOTf). In order to keep the number of variables to a minimum, all reactions were carried out using a 1:1 ratio of Ag/L and run in dichloromethane. The nature of the donor atoms, the coordinating ability of the respective counter-anion and the type of solvent used in recrystallisation, all affect the structural architecture of the final silver(I) complex, generating monomeric, silver(I) complexes {[AgBF₄(L)₂] (1 L = L1; 2 L = L2; 3 L = L3), [AgOTf(L)₃] (4 L = L1; 5 L = L3), [AgBF₄(L)₃] (2a L = L1; 3a L = L3)} and a 1D polymeric chain {[AgOTf(L3)](n) 6}. The organic acenaphthene ligands L1-L3 adopt a number of ligation modes (bis-monodentate μ₂-η²-bridging, quasi-chelating combining monodentate and η⁶-E(phenyl)-Ag(I) and classical monodentate coordination) with the central silver atom at the centre of a tetrahedral or trigonal planar coordination geometry in each case. The importance of weak interactions in the formation of metal-organic structures is also highlighted by the number of short non-covalent contacts present within each complex.

  4. Investigating Silver Coordination to Mixed Chalcogen Ligands

    Directory of Open Access Journals (Sweden)

    J. Derek Woollins

    2012-11-01

    Full Text Available Six silver(I coordination complexes have been prepared and structurally characterised. Mixed chalcogen-donor acenaphthene ligands L1–L3 [Acenap(EPh(E'Ph] (Acenap = acenaphthene-5,6-diyl; E/E' = S, Se, Te were independently treated with silver(I salts (AgBF4/AgOTf. In order to keep the number of variables to a minimum, all reactions were carried out using a 1:1 ratio of Ag/L and run in dichloromethane. The nature of the donor atoms, the coordinating ability of the respective counter-anion and the type of solvent used in recrystallisation, all affect the structural architecture of the final silver(I complex, generating monomeric, silver(I complexes {[AgBF4(L2] (1 L = L1; 2 L = L2; 3 L = L3, [AgOTf(L3] (4 L = L1; 5 L = L3, [AgBF4(L3] (2a L = L1; 3a L = L3} and a 1D polymeric chain {[AgOTf(L3]n 6}. The organic acenaphthene ligands L1-L3 adopt a number of ligation modes (bis-monodentate μ2-η2-bridging, quasi-chelating combining monodentate and η6-E(phenyl-Ag(I and classical monodentate coordination with the central silver atom at the centre of a tetrahedral or trigonal planar coordination geometry in each case. The importance of weak interactions in the formation of metal-organic structures is also highlighted by the number of short non-covalent contacts present within each complex.

  5. Silica-Supported Arsine Palladium(0) Complex: a Highly Active and Stereoselective Catalyst for Arylation of Butyl Acrylate and Acrylamide

    Institute of Scientific and Technical Information of China (English)

    蔡明中; 赵红; 胡文英

    2005-01-01

    A silica-supported arsine palladium(O) complex has been prepared from y-chloropropyltriethoxysilane via immobilization on fumed silica, followed by reaction with potassium diphenylarsenide and palladium chloride, and then reduction with hydrazine hydrate. The complex has been characterized by X-ray photoelectron spectroscopy (XPS) and it is a highly active and stereoselective catalyst for arylation of butyl acrylate and acrylamide with aryl halides, affording a variety of tram-butyl cinnamates and trans-cinnamamides in high yields.

  6. Copper-Catalyzed Enantioselective Synthesis of α-Hydroxyamine Using Monodentate Phosphoramidites

    Institute of Scientific and Technical Information of China (English)

    DONG,Lin; CUN,Lin-Feng; GONG,Liu-Zhu; MI,Ai-Qiao; JIANG,Yao-Zhong

    2004-01-01

    @@ Development of new methods for the introduction of a nitrogen atom to a carbonyl group is still the most important synthetic target. Cu-catalyzed addition of organozinc reagents to α,β-unsaturated carbonyl compounds has been the subject of intensive investigation.[1] Moreover, trapping of the intermediate Zn-enolates has been achieved using nitrosobenzene. To demonstrate the feasibility of developing enantioselective variants of these tandem C-C bond formations,α,β-unsaturated substrates a~d was subjected to standard reaction conditions using Feringa's (L1*, L2*) and our own phosphoramidite ligands (L3*, L4*). In this reaction, medium to high levels of enantioselectivities were observed.

  7. Ruthenium(II) carbonyl complexes containing chalconates and triphenylphosphine/arsine

    Indian Academy of Sciences (India)

    P Viswanathamurthi; M Muthukumar

    2011-09-01

    A series of new hexa-coordinated ruthenium(II) carbonyl complexes of the type [RuCl(CO)(EPh3)(B)(L1−4)] (4-15) (E = P or As; B = PPh3, AsPh3 or Py; L = 2'-hydroxychalcone) were synthesized from the reaction of [RuHCl(CO)(EPh3)2(B)] (1-3) (E = P or As; B = PPh3, AsPh3 or Py) with equimolar chalcone in benzene under reflux. The new complexes have been characterized by analytical and spectroscopic (IR, electronic, 1H, 31P{1H}, and 13C NMR) methods. On the basis of data obtained, an octahedral structure has been assigned for all the complexes. The complexes exhibit catalytic activity for the oxidation of primary and secondary alcohols into their corresponding aldehydes and ketones in the presence of -methylmorpholine--oxide (NMO) as co-oxidant and were also found to be efficient transfer hydrogenation catalysts. The antifungal properties of the ligands and their complexes have also been examined and compared with standard Bavistin.

  8. Synthesis and transition metal coordination chemistry of a novel hexadentate bispidine ligand.

    Science.gov (United States)

    Comba, Peter; Rudolf, Henning; Wadepohl, Hubert

    2015-02-14

    Reported is the new bispidine-derived hexadentate ligand (L = 3-(2-methylpyridyl)-7-(bis-2-methylpyridyl)-3,7-diazabicyclo[3.3.1]nonane) with two tertiary amine and four pyridine donor groups. This ligand can form heterodinuclear and mononuclear complexes and, in the mononuclear compounds discussed here, the ligand may coordinate as a pentadentate ligand, with one of the bispyridinemethane-based pyridine groups un- or semi-coordinated, or as a hexadentate ligand, leading to a pentagonal pyramidal coordination geometry or, with an additional monodentate ligand, to a heptacoordinate pentagonal bipyramidal structure. The solution and solid state data presented here indicate that, with the relatively small Cu(II) and high-spin Fe(II) ions the fourth pyridine group is only semi-coordinated for steric reasons and, with the larger high-spin Mn(II) ion genuine heptacoordination is observed but with a relatively large distortion in the pentagonal equatorial plane.

  9. Synthesis and structural studies of half-sandwich Cp* rhodium and Cp* iridium complexes featuring mono, bi and tetradentate nitrogen and oxygen donor ligands

    Indian Academy of Sciences (India)

    NARASINGA RAO PALEPU; WERNER KAMINSKY; MOHAN RAO KOLLIPARA

    2017-05-01

    A series of Cp*Rh and Cp*Ir complexes of various nitrogen and oxygen donor ligands were synthesized and characterized. Mono, bi and tetradentate ligands were used to synthesize mononuclear and dinuclear complexes. Schiff base derivatives of picolinic hydrazine and 5-aminoquinoline were used in thesynthesis of complexes 1–8. Among the ligands used for complexation, L1 and L2 act as bidentate, L3 as monodentate and L4 as tetradentate in forming the corresponding complexes. All the complexes were characterized by spectroscopic techniques and the structures of complexes 2, 3, 5 and 7 were unambiguouslycharacterized by single crystal X-ray crystallography. Complexes 2 and 7 were found to have π-π stacking interactions and solvent to complex interactions, respectively. Metal-mediated deprotonation of N-H and monodentate binding of nitrogen are attributed to the formation of neutral complexes whereas ionic complexes are formed by (N,O) bonding.

  10. Preparation, characterization, and antitumor activity of new ethylenediamine platinum(IV) complexes containing mixed carboxylate ligands.

    Science.gov (United States)

    Khokhar, A R; Deng, Y; Kido, Y; Siddik, Z H

    1993-05-01

    A series of ethylenediamine platinum(IV) complexes of the type PtIV(en)XA2 and PtIV(en)X'2A2, where X = 1,1-cyclobutanedicarboxylato or malonato, X' = chloro, cyclobutanecarboxylato, cyclopentanecarboxylato, or cyclohexanecarboxylato, and A = acetato or trifluoroacetato were synthesized and characterized by elemental analysis, infrared, and NMR (13C and 195Pt) spectroscopic techniques. These compounds had good to excellent antitumor activity against murine leukemia L1210 cells. Complexes with axial trifluoroacetate groups were superior to those with acetate ligands. Those possessing both axial trifluoroacetate groups and monodentate bis-carboxylate ligands in the equatorial positions were the most active in the series investigated.

  11. Cationic Gold Clusters Ligated with Differently Substituted Phosphines: Effect of Substitution on Ligand Reactivity and Binding

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Grant E.; Olivares, Astrid M.; Hill, David E.; Laskin, Julia

    2015-01-01

    We present a systematic study of the effect of the number of methyl (Me) and cyclohexyl (Cy) functional groups in monodentate phosphine ligands on the solution-phase synthesis of ligated sub-nanometer gold clusters and their gas-phase fragmentation pathways. Small mixed ligand cationic gold clusters were synthesized using ligand exchange reactions between pre-formed triphenylphosphine ligated (PPh3) gold clusters and monodentate Me- and Cy-substituted ligands in solution and characterized using electrospray ionization mass spectrometry (ESI-MS) and collision-induced dissociation (CID) experiments. Under the same experimental conditions, larger gold-PPh3 clusters undergo efficient exchange of unsubstituted PPh3 ligands for singly Me- and Cy-substituted PPh2Me and PPh2Cy ligands. The efficiency of ligand exchange decreases with an increasing number of Me or Cy groups in the substituted phosphine ligands. CID experiments performed for a series of ligand-exchanged gold clusters indicate that loss of a neutral Me-substituted ligand is preferred over loss of a neutral PPh¬3 ligand while the opposite trend is observed for Cy-substituted ligands. The branching ratio of the competing ligand loss channels is strongly correlated with the electron donating ability of the phosphorous lone pair as determined by the relative proton affinity of the ligand. The results indicate that the relative ligand binding energies increase in the order PMe3 < PPhMe2 < PPh2Me < PPh3< PPh2Cy < PPhCy2< PCy3. Furthermore, the difference in relative ligand binding energies increases with the number of substituted PPh3-mMem or PPh3-mCym ligands (L) exchanged onto each cluster. This study provides the first experimental determination of the relative binding energies of ligated gold clusters containing differently substituted monophosphine ligands, which are important to controlling their synthesis and reactivity in solution. The results also indicate that ligand substitution is an important

  12. Curcumin as the OO bidentate ligand in "2 + 1" complexes with the [M(CO)3]+ (M = Re, 99mTc) tricarbonyl core for radiodiagnostic applications.

    Science.gov (United States)

    Sagnou, Marina; Benaki, Dimitra; Triantis, Charalampos; Tsotakos, Theodoros; Psycharis, Vassilis; Raptopoulou, Catherine P; Pirmettis, Ioannis; Papadopoulos, Minas; Pelecanou, Maria

    2011-02-21

    The synthesis and characterization of "2 + 1" complexes of the [M(CO)(3)](+) (M = Re, (99m)Tc) core with the β-diketones acetylacetone (complexes 2, 8) and curcumin (complexes 5, 10 and 6, 11) as bidentate OO ligands, and imidazole or isocyanocyclohexane as monodentate ligands is reported. The complexes were synthesized by reacting the [NEt(4)](2)[Re(CO)(3)Br(3)] precursor with the β-diketone to generate the intermediate aqua complex fac-Re(CO)(3)(OO)(H(2)O) that was isolated and characterized, followed by replacement of the labile water by the monodentate ligand. All complexes were characterized by mass spectrometry, NMR and IR spectroscopies, and elemental analysis. In the case of complex 2, bearing imidazole as the monodentate ligand, X-ray analysis was possible. The chemistry was successfully transferred at (99m)Tc tracer level. The curcumin complexes 5 and 6, as well as their intermediate aqua complex 4, that bear potential for radiopharmaceutical applications due to the wide spectrum of pharmacological activity of curcumin, were successfully tested for selective staining of β-amyloid plaques of Alzheimer's disease. The fact that the complexes maintain the affinity of the mother compound curcumin for β-amyloid plaques prompts for further exploration of their chemistry and biological properties as radioimaging probes.

  13. Oxidation state-differentiated measurement of aqueous inorganic arsenic by continuous flow electrochemical arsine generation coupled to gas-phase chemiluminescence detection.

    Science.gov (United States)

    Sengupta, Mrinal K; Dasgupta, Purnendu K

    2011-12-15

    The electrochemical reduction of inorganic As on a graphite cathode depends on the current density. We observed that while only inorganic As(III) is reduced to AsH(3) at low current densities, at high current densities both forms of inorganic As are reduced. We describe a unique electrochemical reactor in which the cylindrical anode compartment is isolated from the outer concentric cathode compartment by a Nafion tube in which a hole is deliberately made and the entire anode compartment is inside the cylindrical cavity of a small volume (∼115 μL) cathode chamber. The evolved arsine is then quantitated by gas-phase chemiluminescence (GPCL) reaction with ozone; the latter is generated from oxygen formed during electrolysis. For the dimensions used, inorganic As(III) can be selectively determined at a current of 0.1 A while total inorganic As (both As(III) and As(V)) respond equally at an applied electrolysis current at 0.85 A, without any sample treatment. For a 1-mL sample, the system provides a limit of detection (LOD, S/N = 3) of 0.09 μg/L for total As (i = 0.85 A) and an LOD of 0.76 μg/L for As(III) (i = 0.10 A); As(V) is obtained by difference. Comparison of ICP-MS results for total As in groundwater samples that span a large range of concentration and total inorganic As determined by the present method showed a high correlation (r(2) = 0.9975) and a near unity slope. The basic electrochemical arsine generation technique and current-differentiated oxidation state speciation should be applicable as the front end to many other arsenic measurements techniques, including atomic spectrometry.

  14. Synthesis and characterization of mixed ligand complexes of bio-metals with pyrimidine nucleoside (uridine) and amino acids

    Indian Academy of Sciences (India)

    P Rabindra Reddy; A Mohan Reddy

    2000-12-01

    The mixed ligand complexes of Cu(II), Ni(II) and Co(II) with uridine and amino acids, L-alanine, L-phenylalanine and L-tryptophan were synthesized and characterized by elemental analysis, conductivity data, infrared spectra, electronic spectra and magnetic susceptibility data. In these complexes, the nucleoside (uridine) acts as a monodentate ligand coordinating through O(4) under the conditions of investigation, whereas the amino acids coordinate through the carboxylate oxygen and the amino nitrogen. Distorted octahedral geometry for Cu(II) and octahedral geometries for both Ni(II) and Co(II) are proposed.

  15. Sequestering uranium from UO2(CO3)3(4-) in seawater with amine ligands: density functional theory calculations.

    Science.gov (United States)

    Guo, Xiaojing; Huang, Liangliang; Li, Cheng; Hu, Jiangtao; Wu, Guozhong; Huai, Ping

    2015-06-14

    The polystyrene-supported primary amine -CH2NH2 has shown an at least 3-fold increase in uranyl capacity compared to a diamidoxime ligand on a polystyrene support. This study aims to understand the coordination of substitution complexes from UO2(CO3)3(4-) and amines using density functional theory calculations. Four kinds of amines (diethylamine (DEA), ethylenediamine (EDA), diethylenetriamine (DETA) and triethylenetetramine (TETA)) were selected because they belong to different classes and have different chain lengths. The geometrical structures, electronic structures and the thermodynamic stabilities of various substitution complexes, as well as the trends in their calculated properties were investigated at equilibrium. In these optimized complexes, DEA groups bind to uranyl as monodentate ligands; EDA groups serve as monodentate and bidentate ligands; DETA groups act as monodentate and tridentate ligands; while TETA groups serve as monodentate, bidentate and tridentate ligands. The thermodynamic analysis confirmed that the primary amines coordinate to uranyl more strongly than does the secondary amine. The stabilities of substitution complexes with primary amines were calculated to decrease with increasing chain length of the amine, except for UO2(L2)(2+). Of the complexes analyzed, only UO2L(CO3)2(2-) (L = EDA and DETA) and UO2L2CO3 (L = EDA) were predicted to form from the substitution reactions with UO2(CO3)3(4-) and protonated amines as reactants in aqueous solution. Amines were calculated to be comparable to, or sometimes weaker than, amidoximate in replacing CO3(2-) in UO2(CO3)3(4-) to coordinate to uranium. Therefore, the coordination mechanism, in which amines replace carbonates to bind to uranyl, is not primarily responsible for the experimentally observed 3-fold or greater increase in uranyl capacity of primary amines compared to a diamidoxime ligand. Based on the results of our calculations, we believe that the cation exchange mechanism, in which the

  16. Transition Metal Complexes Coordinated by Water Soluble Phosphane Ligands: How Cyclodextrins Can Alter the Coordination Sphere?

    Directory of Open Access Journals (Sweden)

    Michel Ferreira

    2017-01-01

    Full Text Available The behaviour of platinum(II and palladium(0 complexes coordinated by various hydrosoluble monodentate phosphane ligands has been investigated by 31P{1H} NMR spectroscopy in the presence of randomly methylated β-cyclodextrin (RAME-β-CD. This molecular receptor can have no impact on the organometallic complexes, induce the formation of phosphane low-coordinated complexes or form coordination second sphere species. These three behaviours are under thermodynamic control and are governed not only by the affinity of RAME-β-CD for the phosphane but also by the phosphane stereoelectronic properties. When observed, the low-coordinated complexes may be formed either via a preliminary decoordination of the phosphane followed by a complexation of the free ligand by the CD or via the generation of organometallic species complexed by CD which then lead to expulsion of ligands to decrease their internal steric hindrance.

  17. Preparation, spectroscopy, EXAFS, electrochemistry and pharmacology of new ruthenium(II) carbonyl complexes containing ferrocenylthiosemicarbazone and triphenylphosphine/arsine

    Science.gov (United States)

    Prabhakaran, R.; Anantharaman, S.; Thilagavathi, M.; Kaveri, M. V.; Kalaivani, P.; Karvembu, R.; Dharmaraj, N.; Bertagnolli, H.; Dallemer, F.; Natarajan, K.

    2011-02-01

    A new series of new hetero-bimetallic complexes containing iron and ruthenium of the general formula [RuCl(CO)(B)(EPh 3)(L)] (where E = P or As; B = PPh 3, AsPh 3, py or pip; L = ferrocene derived monobasic bidentate thiosemicarbazone ligand) have been synthesized by the reaction between ferrocene-derived thiosemicarbazones and ruthenium(II) complexes of the type [RuHCl(CO)(B)(EPh 3) 2] (where E = P or As; B = PPh 3, AsPh 3, py or pip). The new complexes have been characterized by elemental analyses, IR, electronic, NMR ( 1H, 13C and 31P), EXAFS (extended X-ray absorption fine structure spectroscopy) and cyclic voltammetric techniques. Antibacterial activity of the new complexes has been screened against Escherichia coli, Vibrio cholerae, and Pseudomonas aeruginosa species.

  18. Sensitization of visible and NIR emitting lanthanide(III) ions in noncentrosymmetric complexes of hexafluoroacetylacetone and unsubstituted monodentate pyrazole.

    Science.gov (United States)

    Ahmed, Zubair; Iftikhar, K

    2013-11-07

    A series of highly volatile eight-coordinate air and moisture stable lanthanide complexes of the type [Ln(hfaa)3(L)2] (Ln = Pr (1), Nd (2), Eu (3), Gd (4), Tb (5), Dy (6), Ho (7), Er (8), Tm (9), and Yb (10); hfaa = anion of hexafluoroacetylacetone and L = pyrazole) have been synthesized and characterized by elemental analysis, IR, ESI-MS(+), and NMR studies. Single-crystal X-ray structures have been determined for the Eu(III) and Dy(III) complexes. These complexes crystallize in the monoclinic space group P2(1)/c. The lanthanide ion in each of these complexes is eight-coordinate with six oxygen atoms from three hfaa and two N-atoms from two pyrazole units, forming a coordination polyhedron best describable as a distorted square antiprism. The NMR spectra reveal that both the pyrazole units remain attached to the metal in solution and the β-diketonate and pyrazole protons are shifted in opposite directions in the case of paramagnetic complexes. The lanthanide-induced chemical shifts are dipolar in nature. The hypersensitive transitions of Nd(III), Ho(III), and Er(III) are sensitive to the environment (solvent), which is reflected by the oscillator strength and band shape of these transitions. The band shape due to the hypersensitive transition of Nd(III) in noncoordinating chloroform and dichloromethane is similar to those of the typical eight-coordinate Nd(III) β-diketonate complexes. The quantum yield and lifetime of Pr(III), Eu(III), Tb(III), Dy(III), and Tm(III) in visible and Pr(III), Nd(III), Dy(III), Ho(III), Er(III) Tm(III), and Yb(III) in the NIR region are sizable. The environment around these metal ions is asymmetric, which leads to increased radiative rates and luminescence efficiencies. The quantum yield of the complexes reveal that ligand-to-metal energy transfer follows the order Eu(III) > Tb(III) ≫ Pr(III) > Dy(III) > Tm(III). Both ligands (hfaa and pyrazole) are good sensitizers for all the visible and NIR emitters effectively, except for Tb

  19. Utilization of mixed ligands to construct diverse Ni(II)-coordination polymers based on terphenyl-2,2‧,4,4‧-tetracarboxylic acid and varied N-donor co-ligands

    Science.gov (United States)

    Wang, Chao; Zhao, Jun; Xia, Liang; Wu, Xue-Qian; Wang, Jian-Fang; Dong, Wen-Wen; Wu, Ya-Pan

    2016-06-01

    Three new coordination polymers, namely, {[Ni(H2L)(bix)(H2O)2]·2h2O}n (1), {[Ni(HL)(Hdpa)(H2O)2]·H2O}n (2), {[Ni(L)0.5(bpp)(H2O)]·H2O}n (3) (H4L=terphenyl-2,2‧,4,4‧-tetracarboxylic acid; bix=1,4-bis(imidazol-1-ylmethyl)benzene; dpa =4,4‧-dipyridylamine; bpp=1,3-bis(4-pyridyl)propane), based on rigid H4L ligand and different N-donor co-ligands, have been synthesized under hydrothermal conditions. Compound 1 features a 3D 4-connected 66-dia-type framework with H4L ligand adopts a μ2-bridging mode with two symmetry-related carboxylate groups in μ1-η1:η0 monodentate mode. Compound 2 displays a 1D [Ni(HL)(Hdpa)]n ribbon chains motif, in which the H4L ligand adopts a μ2-bridging mode with two carboxylate groups in μ1-η1:η1 and μ1-η1:η0 monodentate modes, while 3 possesses a (4,4)-connected 3D frameworks with bbf topology, with H4L ligand displays a μ4-bridging coordination mode. The H4L ligand displays not only different deprotonated forms but also diverse coordination modes and conformations. The structural diversities among 1-3 have been carefully discussed, and the roles of N-donor co-ligands in the self-assembly of coordination polymers have been well documented.

  20. Chelate vs monodentate amine effects. Direct comparison of bis(acetato)amminedichloro(cyclohexylamine)platinum(IV) (JM216) with its N-cyclohexyl-1,3-propanediamine analogue

    Science.gov (United States)

    Lee, Young-A.; Kang, Shin Won; Park, Jong Yul; Jung, Ok-Sang

    2003-10-01

    In order to investigate the chelate effects on physicochemical properties including antitumor activity, new cis, trans, cis,-[Pt IVCl 2L 2(chpda)] complexes (L=OH, OCOCH 3; chpda= N-cyclohexyl-1,3-propanediamine) have been synthesized and characterized. The crystal structure of cis, trans, cis-[Pt IVCl 2(OCOCH 3) 2(chpda)] (monoclinic P2 1/ a, a=7.947(1), b=22.753(11), and c=10.581(3) Å, β=110.70(2)°, V=1790(1) Å 3, Z=4, R=0.0534) shows that the platinum(IV) center adopts a typical octahedral arrangement with two acetate groups in a trans position. The pattern and strength of the intramolecular hydrogen bonds are delicately different from those of JM216. Both in vitro and in vivo (oral) cytotoxicities on mouse leukemia L1210 cell line indicate that the activity of chpda chelate analogue is not better than that of the corresponding compound with two monodentate amines (JM216).

  1. Half-sandwich pentamethylcyclopentadienyl group 9 metal complexes of 2-aminopyridyl ligands: Synthesis, spectral and molecular study

    Indian Academy of Sciences (India)

    Mahesh Kalidasan; Scott Forbes; Yurij Mozharivskyj; Mohan Rao Kollipara

    2015-06-01

    Thereaction of [Cp*M(-Cl)Cl]2 (M = Rh, Ir) with 2-aminopyridyl based ligands lead to the formation of mononuclear neutral complexes of general formula [Cp*MCl2(L)] {where L1= 2-aminopyridine, L2= 2-amino-3-picoline, L3= 2-amino-3-nirtopyridine, and L4= 2-amino-3-pyridine carboxyaldehyde}. The complexes have been characterized by FT-IR, UV-Vis, 1H-13C NMR and mass spectroscopic methods. X-ray crystallographic studies of the complexes have shown typical piano-stool geometry around the metal centre in which 2-aminopyridyl ligand acts as an N-monodentate ligand and the amino functionality is not involved in metal coordination. The intra/intermolecular arrangement is due to hydrogen bonding.

  2. Template synthesis, characterization and antimicrobial activity of some new complexes with isonicotinoyl hydrazone ligands

    Directory of Open Access Journals (Sweden)

    LIVIU MITU

    2009-09-01

    Full Text Available Complexes of Cu(II, Ni(II, Co(II with the 9-anthraldehyde iso-nicotinoyl hydrazone ligand (HL1 and the 3,5-di-tert-butyl-4-hydroxy-benzaldehyde isonicotinoyl hydrazone ligand (H2L2 were synthesized by the template method. The complexes were characterized by analytical analysis, IR, UV-Vis and ESR spectroscopy, magnetic measurements, conductometry and thermal analysis and the two ligands by 1H-NMR spectroscopy. From the elemental analysis, 1:2 (metal:ligand stoichiometry for the complexes of Cu(II, Ni(II with the ligands HL1 and H2L2 and 1:1 (metal:ligand stoichiometry for the complex of Co(II with the ligand HL1 are proposed. The molar conductance data showed that the complexes are non-electrolytes. The magnetic susceptibility results coupled with the electronic and ESR spectra suggested a distorted octahedral geometry for the complexes Ni(II/HL1, Ni(II/H2L2 and Cu(II/H2L2, a tetrahedral stereochemistry for the complex Cu/HL1 and a square-planar geometry for the complex Co/HL1. The IR spectra demonstrated the bidentate coordination of the ligands HL1 and H2L2 by the O=C amide oxygen and the azomethine nitrogen, as well as monodentate coordination of the ligand HL1 by the azomethine nitrogen in the Cu(IIcomplex. The antibacterial activity of the ligands and their metallic complexes were tested against Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae.

  3. Secondary interactions or ligand scrambling? Subtle steric effects govern the iridium(I) coordination chemistry of phosphoramidite ligands.

    Science.gov (United States)

    Osswald, Tina; Rüegger, Heinz; Mezzetti, Antonio

    2010-01-25

    The like and unlike isomers of phosphoramidite (P*) ligands are found to react differently with iridium(I), which is a key to explaining the apparently inconsistent results obtained by us and other research groups in a variety of catalytic reactions. Thus, the unlike diastereoisomer (aR,S,S)-[IrCl(cod)(1 a)] (2 a; cod=1,5-cyclooctadiene, 1 a=(aR,S,S)-(1,1'-binaphthalene)-2,2'-diyl bis(1-phenylethyl)phosphoramidite) forms, upon chloride abstraction, the monosubstituted complex (aR,S,S)-[Ir(cod)(1,2-eta-1 a,kappaP)](+) (3 a), which contains a chelating P* ligand that features an eta(2) interaction between a dangling phenyl group and iridium. Under analogous conditions, the like analogue (aR,R,R)-1 a' gives the disubstituted species (aR,R,R)-[Ir(cod)(1 a',kappaP)(2)](+) (4 a') with monodentate P* ligands. The structure of 3 a was assessed by a combination of X-ray and NMR spectroscopic studies, which indicate that it is the configuration of the binaphthol moiety (and not that of the dangling benzyl N groups) that determines the configuration of the complex. The effect of the relative configuration of the P* ligand on its iridium(I) coordination chemistry is discussed in the context of our preliminary catalytic results and of apparently random results obtained by other groups in the iridium(I)-catalyzed asymmetric allylic alkylation of allylic acetates and in rhodium(I)-catalyzed asymmetric cycloaddition reactions. Further studies with the unlike ligand (aS,R,R)-(1,1'-binaphthalene)-2,2'-diyl bis{[1-(1-naphthalene-1-yl)ethyl]phosphoramidite} (1 b) showed a yet different coordination mode, that is, the eta(4)-arene-metal interaction in (aS,R,R)-[Ir(cod)(1,2,3,4-eta-1 b,kappaP)](+) (3 b).

  4. Mechanisms and origins of switchable chemoselectivity of Ni-catalyzed C(aryl)-O and C(acyl)-O activation of aryl esters with phosphine ligands.

    Science.gov (United States)

    Hong, Xin; Liang, Yong; Houk, K N

    2014-02-05

    Many experiments have shown that nickel with monodentate phosphine ligands favors the C(aryl)-O activation over the C(acyl)-O activation for aryl esters. However, Itami and co-workers recently discovered that nickel with bidentate phosphine ligands can selectively activate the C(acyl)-O bond of aryl esters of aromatic carboxylic acids. The chemoselectivity with bidentate phosphine ligands can be switched back to C(aryl)-O activation when aryl pivalates are employed. To understand the mechanisms and origins of this switchable chemoselectivity, density functional theory (DFT) calculations have been conducted. For aryl esters, nickel with bidentate phosphine ligands cleaves C(acyl)-O and C(aryl)-O bonds via three-centered transition states. The C(acyl)-O activation is more favorable due to the lower bond dissociation energy (BDE) of C(acyl)-O bond, which translates into a lower transition-state distortion energy. However, when monodentate phosphine ligands are used, a vacant coordination site on nickel creates an extra Ni-O bond in the five-centered C(aryl)-O cleavage transition state. The additional interaction energy between the catalyst and substrate makes C(aryl)-O activation favorable. In the case of aryl pivalates, nickel with bidentate phosphine ligands still favors the C(acyl)-O activation over the C(aryl)-O activation at the cleavage step. However, the subsequent decarbonylation generates a very unstable tBu-Ni(II) intermediate, and this unfavorable step greatly increases the overall barrier for generating the C(acyl)-O activation products. Instead, the subsequent C-H activation of azoles and C-C coupling in the C(aryl)-O activation pathway are much easier, leading to the observed C(aryl)-O activation products.

  5. Assembly of tetra, di and mononuclear molecular cadmium phosphonates using 2,4,6-triisopropylphenylphosponic acid and ancillary ligands.

    Science.gov (United States)

    Chandrasekhar, Vadapalli; Sasikumar, Palani; Boomishankar, Ramamoorthy

    2008-10-14

    The reaction of ArPO(3)H(2) (Ar = 2,4,6-iPr(3)-C(6)H(2)) with Cd(CH(3)COO)(2).2H(2)O using various co-ligands such as methanol, dimethylformamide (DMF) and 3,5-dimethylpyrazole (DMPZH) resulted in the formation of tetranuclear assemblies [Cd(4)(ArPO(3))(2)(ArPO(3)H)(4)(CH(3)OH)(4)].3(CH(3)OH) (1), [Cd(4)(ArPO(3))(2)(ArPO(3)H)(4)(DMF)(4)].3(DMF) (2) and [Cd(4)(ArPO(3))(2)(ArPO(3)H)(4)(DMF)(2)(DMPZH)(2)].2(DMF).2(H(2)O) (3). In all of these compounds the tetranuclear cadmium array, containing two five-coordinate and two six-coordinate cadmium atoms, is held together by two mu(4) capping [ArPO(3)](2-) and four anisobidentate mu(2) [ArPO(2)(OH)](-) ligands. Each cadmium atom is bound to an additional ancillary ligand. The reaction of ArPO(3)H(2) with Cd(CH(3)COO)(2).2H(2)O in the presence of the chelating ligand 2,2'-bipyridine (bipy) leads to the exclusive formation of the dinuclear assembly [Cd(2)(ArPO(3)H)(4)(bipy)(2)].(CH(3)OH)(H(2)O) (4). The latter contains an eight-membered Cd(2)P(2)O(4) inorganic ring formed as a result of the bridging coordination action of two anisobidentate mu(2) [ArPO(2)(OH)](-) ligands. Each cadmium atom is bound by one chelating bipy and one monodentate [ArPO(2)(OH)](-) ligands. Use of four equivalents of 3,5-dimethylpyrazole leads to the formation of the mononuclear derivative [Cd(ArPO(3)H)(2)(DMPZH)(4)] (5). The molecular structure of the latter comprises of a central cadmium atom surrounded by six monodentate ligands. Four of these are neutral pyrazole ligands that occupy the equatorial plane; the remaining two are anionic phosphinate ligands which are present trans to each other. The thermal analysis of 1 and 4 reveals that the char residue obtained at 600 degrees C consists predominantly of Cd(2)P(2)O(7).

  6. Nonacarbonyl-1κ3C,2κ3C,3κ3C-μ-bis(diphenylarsinomethane-1:2κ2As:As'-[tris(2-chloroethyl phosphite-3κP]-triangulo-triruthenium(0

    Directory of Open Access Journals (Sweden)

    Omar bin Shawkataly

    2010-08-01

    Full Text Available In the title triangulo-triruthenium(0 compound, [Ru3(C25H22As2(C6H12Cl3O3P(CO9], the bis(diphenylarsinomethane ligand bridges an Ru—Ru bond and the monodentate phosphine ligand bonds to the third Ru atom. Both the arsine and phosphine ligands are equatorial with respect to the Ru3 triangle. In addition, each Ru atom carries one equatorial and two axial terminal carbonyl ligands. In the crystal packing, the molecules are linked by intermolecular C—H...O hydrogen bonds into a three-dimensional framework. Weak intermolecular C—H...π interactions further stabilize the crystal structure.

  7. Mixed Ligand Complexes of N-Methyl-N-phenyl Dithiocarbamate: Synthesis, Characterisation, Antifungal Activity, and Solvent Extraction Studies of the Ligand.

    Science.gov (United States)

    Ekennia, Anthony C; Onwudiwe, Damian C; Ume, Cyril; Ebenso, Eno E

    2015-01-01

    A series of mixed ligand dithiocarbamate complexes with a general formula [ML2(py)2], where M = Mn(II), Co(II), Ni(II), and Cu(II), py = pyridine, and L = N-methyl-N-phenyl dithiocarbamate have been prepared and characterised by elemental analysis, FTIR and Uv spectroscopy, magnetic moment, and thermogravimetric and conductance analysis. The infrared spectra showed that symmetrical bidentate coordination occurred with the dithiocarbamate moiety through the sulfur atoms, while neutral monodentate coordination occurred through the nitrogen atom for the pyridine molecule in the complexes. The electronic spectra, elemental analysis, and magnetic moment results proved that the complexes adopted octahedral geometry. The conductance measurement showed that the complexes are nonelectrolytes proving their nonionic nature. The compounds were screened for three human pathogenic fungi: Aspergillus flavus, Aspergillus niger, and Candida albicans. The cobalt complex showed the best antifungal activity among the test compounds. Liquid-liquid extractive abilities of the ligand towards copper and nickel ions in different solvent media were investigated. The ligand showed a strong binding affinity towards the metals ions with an extractive efficiency of about 99%.

  8. Understanding the complexation of Eu3 + with potential ligands used for preferential separation of lanthanides and actinides in various stages of nuclear fuel cycle: A luminescence investigation

    Science.gov (United States)

    Sengupta, Arijit; Kadam, R. M.

    2017-02-01

    A systematic photoluminescence based investigation was carried out to understand the complexation of Eu3 + with different ligands (TBP: tri-n-butyl phosphate, DHOA: di-n-hexyl octanamide, Cyanex 923: tri-n-alkyl phosphine oxide and Cyanex 272: Bis (2,4,4 trimethyl) pentyl phosphinic acid) used for preferential separation of lanthanides and actinides in various stages of nuclear fuel cycle. In case of TBP and DHOA complexes, 3 ligand molecules coordinated in monodentate fashion and 3 nitrate ion in bidentate fashion to Eu3 + to satisfy the 9 coordination of Eu. In case of Cyanex 923 and Cyanex 272 complexes, 3 ligand molecules, 3 nitrate ion and 3 water molecules coordinated to Eu3 + in monodentate fashion. The Eu complexes of TBP and DHOA were found to have D3h local symmetry while that for Cyanex 923 and Cyanex 272 were C3h. Judd-Ofelt analysis of these systems revealed that the covalency of Eusbnd O bond followed the trend DHOA > TBP > Cyanex 272 > Cyanex 923. Different photophysical properties like radiative and non-radiative life time, branching ratio for different transitions, magnetic and electric dipole moment transition probabilities and quantum efficiency were also evaluated and compared for these systems. The magnetic dipole transition probability was found to be almost independent of ligand field perturbation while electric dipole transition probability for 5D0-7F2 transition was found to be hypersensitive with ligand field with a trend DHOA > TBP > Cyanex 272 > Cyanex 923. Supplementary Table 2: Determination of inner sphere water molecules from the different empirical formulae reported in the literature.

  9. Antitumor and antiparasitic activity of novel ruthenium compounds with polycyclic aromatic ligands.

    Science.gov (United States)

    Miserachs, Helena Guiset; Cipriani, Micaella; Grau, Jordi; Vilaseca, Marta; Lorenzo, Julia; Medeiros, Andrea; Comini, Marcelo A; Gambino, Dinorah; Otero, Lucía; Moreno, Virtudes

    2015-09-01

    Five novel ruthenium(II)-arene complexes with polycyclic aromatic ligands were synthesized, comprising three compounds of the formula [RuCl(η(6)-p-cym)(L)][PF6], where p-cym = 1-isopropyl-4-methylbenzene and L are the bidentate aromatic ligands 1,10-phenanthroline-5,6-dione, 1, 5-amine-1,10-phenanthroline, 4, or 5,6-epoxy-5,6-dihydro-phenanthroline, 5. In the other two complexes [RuCl2(η(6)-p-cym)(L')], the metal is coordinated to a monodentate ligand L', where L' is phenanthridine, 2, or 9-carbonylanthracene, 3. All compounds were fully characterized by mass spectrometry and elemental analysis, as well as NMR and IR spectroscopic techniques. Obtained ruthenium compounds as well as their respective ligands were tested for their antiparasitic and antitumoral activities. Even though all compounds showed lower Trypanosoma brucei activity than the free ligands, they also resulted less toxic on mammalian cells. Cytotoxicity assays on HL60 cells showed a moderate antitumoral activity for all ruthenium compounds. Compound 1 was the most potent antitumoral (IC50 = 1.26±0.78 μM) and antiparasitic (IC50 = 0.19 ± 0.05 μM) agent, showing high selectivity towards the parasites (selectivity index >100). As complex 1 was the most promising antitumoral compound, its interaction with ubiquitin as potential target was also studied. In addition, obtained ruthenium compounds were found to bind DNA, and they are thought to interact with this macromolecule mainly through intercalation of the aromatic ligand.

  10. Synthesis and Characterization of Phosphine and Arsine Complexes of Ruthenium (Ii & Iii Ligated With 3-(4-Pyridyl-4-Substituted-Triazoline-5-Thione

    Directory of Open Access Journals (Sweden)

    R. N. Pandey

    2014-12-01

    Full Text Available Organometallic complexes of ruthenium (II & III with the formula [RuH(CO(Ef32L] and [RuCl2(Ef32L] (E = P/As; L = deprotonated mononegative bidentate 3-(4-pyridyl-triazoline-5-thione and its 4-phenyl substituted derivative were synthesized and characterized by elemental analysis, physico-chemical and spectroscopic methods. All new compounds were iso-structural with precursor complexes. Two triphenyl phosphine or triphenylarsine molecules are at trans-disposition and thioamide ligands behaves as bidentate (N, S donor in assigned octahedral structure.

  11. Multivariate regression analysis on influencing factors related to arsenic content in urine of arsine exposed workers%砷化氢作业工人尿中砷含量相关因素的多元线性回归分析

    Institute of Scientific and Technical Information of China (English)

    韦光毅; 柳元; 胡天桥; 陈启玲

    2012-01-01

    目的 分析寻找砷化氢作业工人的尿中砷含量的主要影响因素,为预防砷化氢中毒提供参考.方法 收集132例砷化氢作业工人的尿砷水平及其相关因素的详细资料,采用多元逐步回归和多元线性回归的方法进行统计分析.结果 获得回归方程lgY=0.551 D1+0.281 D2 +0.665X7+0.059X8+0.005 X3 -2.279,决定系数调整R2=0.885,其中D1,D2代表工种的2个虚拟变量,X7代表砷化氢浓度,X8代表自觉症状,X3代表年龄,标准化偏回归系数分别为0.569,0.268,0.624,0.056,0.054.结论 回归方程表明砷化氢作业工人尿砷的主要影响因素为工种、砷化氢浓度,提示预防砷化氢中毒要做好高危工种工人的防护,控制好作业场所空气中砷化氢的浓度.%[ Objective ] To analyze the major factors affecting arsenic levels in urine of workers exposed to arsine, and provide reference for arsine poisoning prevention. [ Methods] Detailed information on arsenic levels in urine and its related factors of 132 cases of workers exposed to arsine was collected. Stepwise multiple regression and multiple linear regression method were used for statistical analysis. [Results] Regression equation was obtained, lg Y = 0. 551 D1 +0. 281 D2 +0. 665 X, + 0. 059 X2 +0. 005 X3-2. 279, adjusted R2 =0. 885, D, , D2 were the two dummy variables of jobs, X7 was the concentration of arsine, X8 was symptoms, X3 was the age. Their standardized partial regression coefficients were 0. 569, 0. 268, 0. 624, 0. 056 and 0. 054. [ Conclusion] The regression equation suggests the main factors affecting arsenic levels in urine of workers exposed to arsine were the types of work and the concentration of arsine, the protection of high-risk workers and the control of air arsine concentration in workplaces should be strengthened.

  12. Synthesis and structural characterization of PHP[(C(5)Me(4))(2)], a monodentate chiral phosphine derived from intramolecular C-C coupling of tetramethylcyclopentadienyl groups: an evaluation of steric and electronic properties.

    Science.gov (United States)

    Shin, J H; Bridgewater, B M; Churchill, D G; Parkin, G

    2001-10-22

    The chiral monodentate phosphine PhP[(C(5)Me(4))(2)] is readily obtained by oxidation of the lithium complex Li(2)[PhP(C(5)Me(4))(2)] with I(2), which couples the two cyclopentadienyl groups to form a five-membered heterocyclic ring. The steric and electronic properties of PhP[(C(5)Me(4))(2)] have been evaluated by X-ray diffraction and IR spectroscopic studies on a variety of derivatives, including Ph[(C(5)Me(4))(2)]PE (E = S, Se), Cp*MCl(4)[P[(C(5)Me(4))(2)]Ph] (M = Mo, Ta), Ir[P[(C(5)Me(4))(2)]Ph](2)(CO)Cl, and CpFe(CO)[PhP[(C(5)Me(4))(2)

  13. A density functional theory investigation of the interaction of the tetraaqua calcium cation with bidentate carbonyl ligands.

    Science.gov (United States)

    Quattrociocchi, Daniel Garcez S; Meuser, Marcos Vinicius Monsores; Ferreira, Glaucio Braga; de M Carneiro, José Walkimar; Stoyanov, Stanislav R; da Costa, Leonardo Moreira

    2017-02-01

    Calcium complexes with bidentate carbonyl ligands are important in biological systems, medicine and industry, where the concentration of Ca(2+) is controlled using chelating ligands. The exchange of two water molecules of [Ca(H2O)6](2+) for one bidentate monosubstituted and homo disubstituted dicarbonyl ligand was investigated using the B3LYP/6-311++G(d,p) method. The ligand substituents NH2, OCH3, OH, CH3, H, F, Cl, CN and NO2 are functional groups with distinct electron-donating and -withdrawing effects that bond directly to the sp(2) C atom of the carbonyl group. The geometry, charge and energy characteristics of the complexes were analyzed to help understand the effects of substituents, spacer length and chelation. Coordination strength was quantified in terms of the enthalpy and free energy of the exchange reaction. The most negative enthalpies were calculated for the coordination of bidentate ligands containing three to five methylene group spacers between carbonyls. The chelate effect contribution was analyzed based on the thermochemistry. The electronic character of the substituent modulates the strength of binding to the metal cation, as ligands containing electron-donor substituents coordinate stronger than those with electron-acceptor substituents. This is reflected in the geometric (bond length and chelating angle), electronic (atomic charges) and energetic (components of the total interacting energy) characteristics of the complexes. Energy decomposition analysis (EDA)-an approach for partitioning of the energy into its chemical origins-shows that the electrostatic component of the coordination is predominant, and yields relevant contribution of the covalent term, especially for the electron-withdrawing substituted ligands. The chelate effect of the bidentate ligands was noticeable when compared with substitution by two monodentate ligands. Graphical abstract The affinity of 18 bidentate carbonyl ligands toward the [Ca(H2O)4](2+) cation is evaluated in

  14. 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.

  15. Investigation of antitumor potential of Ni(II) complexes with tridentate PNO acylhydrazones of 2-(diphenylphosphino)benzaldehyde and monodentate pseudohalides.

    Science.gov (United States)

    Čobeljić, Božidar; Milenković, Milica; Pevec, Andrej; Turel, Iztok; Vujčić, Miroslava; Janović, Barbara; Gligorijević, Nevenka; Sladić, Dušan; Radulović, Siniša; Jovanović, Katarina; Anđelković, Katarina

    2016-04-01

    Square-planar azido Ni(II) complex with condensation product of 2-(diphenylphosphino)benzaldehyde and Girard's T reagent was synthesized and its crystal structure was determined. Cytotoxic activity of the azido complex and previously synthesized isothiocyanato, cyanato and chlorido Ni(II) complexes with this ligand was examined on six tumor cell lines (HeLa, A549, K562, MDA-MB-453, MDA-MB-361 and LS-174) and two normal cell line (MRC-5 and BEAS-2B). All the investigated nickel(II) complexes were cytotoxic against all tumor cell lines. The newly synthesized azido complex showed selectivity to HeLa and A549 tumor cell lines compared to the normal cells (for A549 IC50 was similar to that of cisplatin). Azido complex interferes with cell cycle phase distribution of A549 and HeLa cells and possesses nuclease activity towards supercoiled DNA. The observed selectivity of the azido complex for some tumor cell lines can be connected with its strong DNA damaging activity.

  16. Ligand modeling and design

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-10-01

    The purpose of this work is to develop and implement a molecular design basis for selecting organic ligands that would be used tin applications for the cost-effective removal of specific radionuclides from nuclear waste streams.

  17. [μ-Bis(diphenyl-arsino)methane-1:2κAs:As'][bis-(4-methoxy-phen-yl)phenyl-phosphine-3κP]-nona-carbonyl-1κC,2κC,3κC-triangulo-tri-ruthenium(0) dichloro-methane 0.15-solvate.

    Science.gov (United States)

    Shawkataly, Omar Bin; Khan, Imthyaz Ahmed; Yeap, Chin Sing; Fun, Hoong-Kun

    2010-01-30

    The asymmetric unit of the title triangulo-triruthenium compound, [Ru(3)(C(25)H(22)As(2))(C(20)H(19)O(2)P)(CO)(9)]·0.15CH(2)Cl(2), contains one mol-ecule of the triangulo-triruthenium complex and one partially occupied dichloro-methane solvent mol-ecule. The dichloro-methane solvent lies across a crystallographic inversion center leading to the mol-ecule being disordered over two positions of equal occupancy. The bis-(diphenyl-arsino)methane ligand bridges an Ru-Ru bond and the monodentate arsine ligand bonds to the third Ru atom. Both the arsine ligands are equatorial with respect to the Ru(3) triangle. In addition, each Ru atom carries one equatorial and two axial terminal carbonyl ligands. The three phospho-rus-bound benzene rings make dihedral angles of 72.7 (3), 80.9 (3) and 70.8 (2)° with each other. The dihedral angles between the two benzene rings are 79.9 (3) and 81.5 (2)° for the two diphenyl-arsino groups.

  18. Hexacoordinate Silicon Compounds with a Dianionic Tetradentate (N,N′,N′,N-Chelating Ligand

    Directory of Open Access Journals (Sweden)

    Daniela Gerlach

    2016-04-01

    Full Text Available In the context of our systematic investigations of penta- and hexacoordinate silicon compounds, which included dianionic tri- (O,N,O′; O,N,N′ and tetradentate (O,N,N,O; O,N,N′,O′ chelators, we have now explored silicon coordination chemistry with a dianionic tetradentate (N,N′,N′,N chelator. The ligand [o-phenylene-bis(pyrrole-2-carbaldimine, H2L] was obtained by condensation of o-phenylenediamine and pyrrole-2-carbaldehyde and subsequently silylated with chlorotrimethylsilane/triethylamine. Transsilylation of this ligand precursor (Me3Si2L with chlorosilanes SiCl4, PhSiCl3, Ph2SiCl2, (Anis2SiCl2 and (4-Me2N-C6H4PhSiCl2 afforded the hexacoordinate Si complexes LSiCl2, LSiPhCl, LSiPh2, LSi(Anis2 and LSiPh(4-Me2N-C6H4, respectively (Anis = anisyl = 4-methoxyphenyl. 29Si NMR spectroscopy and, for LSiPh2, LSi(Anis2 and LSiPh(4-Me2N-C6H4, single-crystal X-ray diffraction confirm hexacoordination of the Si atoms. The molecular structures of LSiCl2 and LSiPhCl were elucidated by computational methods. Despite the two different N donor sites (pyrrole N, X-type donor; imine N, L-type donor, charge delocalization within the ligand backbone results in compounds with four similar Si–N bonds. Charge distribution within the whole molecules was analyzed by calculating the Natural Charges (NCs. Although these five compounds carry electronically different monodentate substituents, their constituents reveal rather narrow ranges of their charges (Si atoms: +2.10–+2.22; monodentate substituents: −0.54–−0.56; L2−: −1.02–−1.11.

  19. Influence of functionalized pyridine ligands on the radio/chemical behavior of [M(I)(CO)3](+) (M = Re and (99m)Tc) 2 + 1 complexes.

    Science.gov (United States)

    Hayes, Thomas R; Lyon, Patrice A; Barnes, Charles L; Trabue, Steven; Benny, Paul D

    2015-02-16

    While a number of chelate strategies have been developed for the organometallic precursor fac-[M(I)(OH2)3(CO)3](+) (M = Re, (99m)Tc), a unique challenge has been to improve the overall function and performance of these complexes for in vivo and in vitro applications. Since its discovery, fac-[M(I)(OH2)3(CO)3](+) has served as an essential scaffold for the development of new targeted (99m)Tc based radiopharmaceuticals due to its labile aquo ligands. However, the lipophilic nature of the fac-[M(I)(CO)3](+) core can influence the in vivo pharmacokinetics and biodistribution of the complexes. In an effort to understand and improve this behavior, monosubstituted pyridine ligands were used to assess the impact of donor nitrogen basicity on binding strength and stability of fac-[M(I)(CO)3](+) in a 2 + 1 labeling strategy. A series of Re and (99m)Tc complexes were synthesized with picolinic acid as a bidentate ligand and 4-substituted pyridine ligands. These complexes were designed to probe the effect of pKa from the monodentate pyridine ligand both at the macro scale and radiochemical concentrations. Comparison of X-ray structural data and radiochemical solution experiments clearly indicate an increase in overall yield and stability as pyridine basicity increased.

  20. Photochemistry of RuII 4,4′-Bi-1,2,3-triazolyl (btz) Complexes: Crystallographic Characterization of the Photoreactive Ligand-Loss Intermediate trans-[Ru(bpy)(κ2-btz)(κ1-btz)(NCMe)]2+

    Science.gov (United States)

    Welby, Christine E; Armitage, Georgina K; Bartley, Harry; Wilkinson, Aaron; Sinopoli, Alessandro; Uppal, Baljinder S; Rice, Craig R; Elliott, Paul I P

    2014-01-01

    We report the unprecedented observation and unequivocal crystallographic characterization of the meta-stable ligand loss intermediate solvento complex trans-[Ru(bpy)(κ2-btz)(κ1-btz)(NCMe)]2+ (1 a) that contains a monodentate chelate ligand. This and analogous complexes can be observed during the photolysis reactions of a family of complexes of the form [Ru()(btz)2]2+ (1 a–d: btz=1,1′-dibenzyl-4,4′-bi-1,2,3-triazolyl; =a) 2,2′-bipyridyl (bpy), b) 4,4′-dimethyl-2,2′-bipyridyl (dmbpy), c) 4,4′-dimethoxy-2,2′-bipyridyl (dmeobpy), d) 1,10-phenanthroline (phen)). In acetonitrile solutions, 1 a–d eventually convert to the bis-solvento complexes trans-[Ru()(btz)(NCMe)2]2+ (3 a–d) along with one equivalent of free btz, in a process in which the remaining coordinated bidentate ligands undergo a new rearrangement such that they become coplanar. X-ray crystal structure of 3 a and 3 d confirmed the co-planar arrangement of the and btz ligands and the trans coordination of two solvent molecules. These conversions proceed via the observed intermediate complexes 2 a–d, which are formed quantitatively from 1 a–d in a matter of minutes and to which they slowly revert back on being left to stand in the dark over several days. The remarkably long lifetime of the intermediate complexes (>12 h at 40 °C) allowed the isolation of 2 a in the solid state, and the complex to be crystallographically characterized. Similarly to the structures adopted by complexes 3 a and d, the bpy and κ2-btz ligands in 2 a coordinate in a square-planar fashion with the second monodentate btz ligand coordinated trans to an acetonitrile ligand. PMID:24889966

  1. 2-Acylpyrroles as mono-anionic O,N-chelating ligands in silicon coordination chemistry.

    Science.gov (United States)

    Kämpfe, Alexander; Brendler, Erica; Kroke, Edwin; Wagler, Jörg

    2014-07-21

    Kryptopyrrole (2,4-dimethyl-3-ethylpyrrole) was acylated with, for example, benzoyl chloride to afford 2-benzoyl-3,5-dimethyl-4-ethylpyrrole (L(1)H). With SiCl4 this ligand reacts under liberation of HCl and formation of the complex L(1)2SiCl2. In related reactions with HSiCl3 or H2SiCl2, the same chlorosilicon complex is formed under liberation of HCl and H2 or liberation of H2, respectively. The chlorine atoms of L(1)2SiCl2 can be replaced by fluoride and triflate using ZnF2 and Me3Si-OTf, respectively. The use of a supporting base (triethylamine) is required for the complexation of phenyltrichlorosilane and diphenyldichlorosilane. The complexes L(1)2SiCl2, L(1)2SiF2, L(1)2Si(OTf)2, L(1)2SiPhCl, and L(1)2SiPh2 exhibit various configurations of the octahedral silicon coordination spheres (i.e. cis or trans configuration of the monodentate substituents, different orientations of the bidentate chelating ligands relative to each other). Furthermore, cationic silicon complexes L(1)3Si(+) and L(1) SiPh(+) were synthesized by chloride abstraction with GaCl3. In contrast, reaction of L(1)2SiCl2 with a third equivalent of L(1)H in the presence of excess triethylamine produced a charge-neutral hexacoordinate Si complex with a new tetradentate chelating ligand which formed by Si-templated C-C coupling of two ligands L(1).

  2. Syntheses and Structures of Two Mixed Ligands Lanthanide Complexes with N,N'-Substituted Adipamide

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Crystal structures of neodymium (Ⅲ) and dysprosium (Ⅲ) nitrate complexes with the new ligand N, N'-dimethyl-N, N'-diphenyladipamide (mpaa) has been determined. Both complexes are triclinic with space group Pi ,formula [C22H30N5NdO12S]2 1 [C42H54N7DyO14S 2]Mr = 1465.62[1075.48], a = 8.541(1)[9.711(2)], b = 11.915(1)[16.017(3)], c = 15.906(1)[16.686(3)] A,α =107.22(1)[109.600(1)],β = 98.12(1)[92.50(1)], γ = 99.78(1) [96.22(1)]° ,μ=0.71073cn-1; R=0.0261 [0.0364], wR=0.0611 [0.0857] reflections with I>2 σ (Ⅰ). Complex (1)is dinuclear, in which two Nd(Ⅲ) ions are double-bridged by two mpaa ligands. And Dy(mpaa)2(dmso)(NO3)3 (2) (dmso= dimethylsulfoxide) is a mononuclear complex, in which one of the two C=O groups in MPAA is uncoordinated. In the two above complexes, each Ln(Ⅲ)ion is nine-coordinated including three bidenate nitrates, one dmso molecule and two carbonyl oxygens from two different mpaa ligands. Neutral monodentate dmso enters the coordination in diamides of the type (R1R2NCO)2(CH2)n was increased, the ligand prefers to act as a bridging reagent rather than a chelate.

  3. Ligand fitting with CCP4

    Science.gov (United States)

    2017-01-01

    Crystal structures of protein–ligand complexes are often used to infer biology and inform structure-based drug discovery. Hence, it is important to build accurate, reliable models of ligands that give confidence in the interpretation of the respective protein–ligand complex. This paper discusses key stages in the ligand-fitting process, including ligand binding-site identification, ligand description and conformer generation, ligand fitting, refinement and subsequent validation. The CCP4 suite contains a number of software tools that facilitate this task: AceDRG for the creation of ligand descriptions and conformers, Lidia and JLigand for two-dimensional and three-dimensional ligand editing and visual analysis, Coot for density interpretation, ligand fitting, analysis and validation, and REFMAC5 for macromolecular refinement. In addition to recent advancements in automatic carbohydrate building in Coot (LO/Carb) and ligand-validation tools (FLEV), the release of the CCP4i2 GUI provides an integrated solution that streamlines the ligand-fitting workflow, seamlessly passing results from one program to the next. The ligand-fitting process is illustrated using instructive practical examples, including problematic cases such as post-translational modifications, highlighting the need for careful analysis and rigorous validation. PMID:28177312

  4. LigandRNA: computational predictor of RNA-ligand interactions.

    Science.gov (United States)

    Philips, Anna; Milanowska, Kaja; Lach, Grzegorz; Bujnicki, Janusz M

    2013-12-01

    RNA molecules have recently become attractive as potential drug targets due to the increased awareness of their importance in key biological processes. The increase of the number of experimentally determined RNA 3D structures enabled structure-based searches for small molecules that can specifically bind to defined sites in RNA molecules, thereby blocking or otherwise modulating their function. However, as of yet, computational methods for structure-based docking of small molecule ligands to RNA molecules are not as well established as analogous methods for protein-ligand docking. This motivated us to create LigandRNA, a scoring function for the prediction of RNA-small molecule interactions. Our method employs a grid-based algorithm and a knowledge-based potential derived from ligand-binding sites in the experimentally solved RNA-ligand complexes. As an input, LigandRNA takes an RNA receptor file and a file with ligand poses. As an output, it returns a ranking of the poses according to their score. The predictive power of LigandRNA favorably compares to five other publicly available methods. We found that the combination of LigandRNA and Dock6 into a "meta-predictor" leads to further improvement in the identification of near-native ligand poses. The LigandRNA program is available free of charge as a web server at http://ligandrna.genesilico.pl.

  5. Synthesis and characterization of a cadmium(II)-organic supramolecular coordination compound based on the multifunctional 2-amino-5-sulfobenzoic acid ligand.

    Science.gov (United States)

    Yuan, Gan Yin; Zhang, Lei; Wang, Meng Jie; Zhang, Kou Lin

    2016-12-01

    Much attention has been paid by chemists to the construction of supramolecular coordination compounds based on the multifunctional ligand 5-sulfosalicylic acid (H3SSA) due to the structural and biological interest of these compounds. However, no coordination compounds have been reported for the multifunctional amino-substituted sulfobenzoate ligand 2-amino-5-sulfobenzoic acid (H2asba). We expected that H2asba could be a suitable building block for the assembly of supramolecular networks due to its interesting structural characteristics. The reaction of cadmium(II) nitrate with H2asba in the presence of the auxiliary flexible dipyridylamide ligand N,N'-bis[(pyridin-4-yl)methyl]oxamide (4bpme) under ambient conditions formed a new mixed-ligand coordination compound, namely bis(3-amino-4-carboxybenzenesulfonato-κO(1))diaquabis{N,N'-bis[(pyridin-4-yl)methyl]oxamide-κN}cadmium(II)-N,N'-bis[(pyridin-4-yl)methyl]oxamide-water (1/1/4), [Cd(C7H6NO5S)2(C14H14N4O2)2(H2O)2]·C14H14N4O2·4H2O, (1), which was characterized by single-crystal and powder X-ray diffraction analysis (PXRD), FT-IR spectroscopy, thermogravimetric analysis (TG), and UV-Vis and photoluminescence spectroscopic analyses in the solid state. The central Cd(II) atom in (1) occupies a special position on a centre of inversion and exhibits a slightly distorted octahedral geometry, being coordinated by two N atoms from two monodentate 4bpme ligands, four O atoms from two monodentate 4-amino-3-carboxybenzenesulfonate (Hasba(-)) ligands and two coordinated water molecules. Interestingly, complex (1) further extends into a threefold polycatenated 0D→2D (0D is zero-dimensional and 2D is two-dimensional) interpenetrated supramolecular two-dimensional (4,4) layer through intermolecular hydrogen bonding. The interlayer hydrogen bonding further links adjacent threefold polycatenated two-dimensional layers into a three-dimensional network. The optical properties of complex (1) indicate that it may be used as a

  6. Analysis of macromolecules, ligands and macromolecule-ligand complexes

    Science.gov (United States)

    Von Dreele, Robert B [Los Alamos, NM

    2008-12-23

    A method for determining atomic level structures of macromolecule-ligand complexes through high-resolution powder diffraction analysis and a method for providing suitable microcrystalline powder for diffraction analysis are provided. In one embodiment, powder diffraction data is collected from samples of polycrystalline macromolecule and macromolecule-ligand complex and the refined structure of the macromolecule is used as an approximate model for a combined Rietveld and stereochemical restraint refinement of the macromolecule-ligand complex. A difference Fourier map is calculated and the ligand position and points of interaction between the atoms of the macromolecule and the atoms of the ligand can be deduced and visualized. A suitable polycrystalline sample of macromolecule-ligand complex can be produced by physically agitating a mixture of lyophilized macromolecule, ligand and a solvent.

  7. Ligand-Receptor Interactions

    CERN Document Server

    Bongrand, Pierre

    2008-01-01

    The formation and dissociation of specific noncovalent interactions between a variety of macromolecules play a crucial role in the function of biological systems. During the last few years, three main lines of research led to a dramatic improvement of our understanding of these important phenomena. First, combination of genetic engineering and X ray cristallography made available a simultaneous knowledg of the precise structure and affinity of series or related ligand-receptor systems differing by a few well-defined atoms. Second, improvement of computer power and simulation techniques allowed extended exploration of the interaction of realistic macromolecules. Third, simultaneous development of a variety of techniques based on atomic force microscopy, hydrodynamic flow, biomembrane probes, optical tweezers, magnetic fields or flexible transducers yielded direct experimental information of the behavior of single ligand receptor bonds. At the same time, investigation of well defined cellular models raised the ...

  8. Excited state intramolecular proton transfer (ESIPT) in six-coordinated zinc(ii)-quinoxaline complexes with ligand hydrogen bonds: their fluorescent properties sensitive to axial positions.

    Science.gov (United States)

    Sakai, Ken-Ichi; Takahashi, Sami; Kobayashi, Ataru; Akutagawa, Tomoyuki; Nakamura, Takayoshi; Dosen, Masaaki; Kato, Masako; Nagashima, Umpei

    2010-02-28

    Zinc(ii)-quinoxaline complexes, [Zn(hqxc)(2)(py)(2)] and [Zn(hqxc)(2)(DMSO)(2)] (hqxc = 3-hydroxy-2-quinoxalinecarboxylate, py = pyridine, DMSO = dimethyl sulfoxide), were prepared and characterized by X-ray crystallography and fluorescence spectroscopy. In both complexes, the zinc ion is six-coordinated by two equatorial bidentate hqxc ligands with an intramolecular hydrogen bond and two axial monodentate ligands such as pyridine or DMSO. In spite of similar coordination geometries, there is a remarkable difference between their solid-state fluorescent properties. The pyridine complex is strongly fluorescent (fluorescence quantum yield Phi = 0.22), giving rise to a significantly Stokes-shifted spectrum. From its thin film photopumped by a nitrogen gas laser, amplified spontaneous emission was observed. These results suggest that the fluorescence occurs by way of excited-state intramolecular proton-transfer (ESIPT) in the hydrogen bond of hqxc. On the other hand, the DMSO complex shows fluorescent intensity (Phi = 0.08) lower than that of the pyridine complex, and shows normal emission in addition to ESIPT emission. From IR measurements for these complexes, it is concluded that axial ligands influence the hydrogen bond strength of the equatorial hqxc ligand via zinc and thus the ESIPT efficiency.

  9. Quinoxaline-2-carboxamide as a carrier ligand in two new platinum(II) compounds: Synthesis, crystal structure, cytotoxic activity and DNA interaction.

    Science.gov (United States)

    Marqués-Gallego, Patricia; Gamiz-Gonzalez, M Amparo; Fortea-Pérez, Francisco R; Lutz, Martin; Spek, Anthony L; Pevec, Andrej; Kozlevčar, Bojan; Reedijk, Jan

    2010-06-01

    The search for platinum compounds structurally different from cisplatin has led to two new platinum(II) compounds containing quinoxaline-2-carboxamide as a carrier ligand, i.e. cis-[Pt(qnxca)(MeCN)Cl2] (1) and the [Pt(qnxca-H)(dmso)Cl] (2). Both compounds have been synthesized and characterized using different spectroscopic methods. In addition, single-crystal structures have been determined by X-Ray diffraction for both compounds. In each case a square planar Pt(II) is present; in (1) the qnxca is monodentate and neutral, whereas in (2) the ligand has lost a hydrogen, to form the anionic chelating ligand abbreviated as qnxca-H. The biological activity of both compounds has been investigated in a panel of seven human tumour cells, displaying poor cytotoxic activity, compared to cisplatin. The interaction of the new compounds with 1 or 2 equiv. of 9-ethylguanine has been studied using (1)H NMR, (195)Pt NMR and ESI-MS spectroscopy, finding poor reactivity of 1 towards the model base, forming only the monosubstituted adduct. Surprisingly, compound 2, which is more sterically crowded, interacts more efficiently with the 9-EtG, forming a bifunctional adduct with two 9-EtG with substitution of the dmso and the chloride ligand. Unwinding studies of pUC19 plasmid DNA by compound 1 show similar unwinding properties to cisplatin.

  10. A one-dimensional copper(II) coordination polymer incorporating succinate and N,N-diethylethylenediamine ligands: crystallographic analysis, vibrational and surface features, and DFT analysis.

    Science.gov (United States)

    Şen, Fatih; Kansiz, Sevgi; Uçar, İbrahim

    2017-07-01

    Transition metal atoms can be bridged by aliphatic dicarboxylate ligands to produce chains, layers and frameworks. The reaction of copper sulfate with succinic acid (H2succ) and N,N-diethylethylenediamine (deed) in basic solution produces the complex catena-poly[[[(N,N-diethylethylenediamine-κ(2)N,N')copper(II)]-μ-succinato-κ(2)O(1):O(4)] tetrahydrate], {[Cu(C4H4O4)(C6H16N2)]·4H2O}n or {[Cu(succ)(deed)]·4H2O}n. Each carboxylate group of the succinate ligand coordinates to a Cu(II) atom in a monodentate fashion, giving rise to a square-planar coordination environment. The succinate ligands bridge the Cu(II) centres to form one-dimensional polymeric chains. Hydrogen bonds between the ligands and water molecules link these chains into sheets that lie in the ab plane. Density functional theory (DFT) calculations were used to support the experimental data. From these calculations, a good linear correlation was observed between the experimental and theoretically predicted structural and spectroscopic parameters (R(2) ∼ 0.97).

  11. Therapeutic androgen receptor ligands

    OpenAIRE

    Allan, George F.; Sui, Zhihua

    2003-01-01

    In the past several years, the concept of tissue-selective nuclear receptor ligands has emerged. This concept has come to fruition with estrogens, with the successful marketing of drugs such as raloxifene. The discovery of raloxifene and other selective estrogen receptor modulators (SERMs) has raised the possibility of generating selective compounds for other pathways, including androgens (that is, selective androgen receptor modulators, or SARMs).

  12. A Hirshfeld surface analysis, crystal structure and physicochemical studies of a new Cd(II) complex with the 2-amino-4-methylpyrimidine ligand

    Science.gov (United States)

    Klai, Kacem; Kaabi, Kamel; Kaminsky, Werner; Jelsch, Christian; Lefebvre, Frédéric; Ben Nasr, Cherif

    2017-01-01

    A new Cd(II) complex with the monodentate ligand 2-amino-4-methylpyrimidine, [Cd(NO3)2(C5N3H7)2(H2O)2], has been prepared and characterized by single crystal X-ray diffraction, elemental analysis, CP-MAS NMR and IR spectroscopy. The basic coordination patterns of the 2-amino-4-methylpyrimidine coordinated metal cations are slightly distorted octahedra in this compound. The crystal structure is characterized by CdN2O4 octahedra interconnected via O-H…O and O-H…N hydrogen bonds to form layers parallel to the (b, c) plane. The crystal structure is stabilized by sets of hydrogen bonds, one of which is trifurcated. Intermolecular interactions were investigated by Hirshfeld surfaces. The 13C and 15N CP-MAS NMR spectra are discussed and the vibrational absorption bands were identified by infrared spectroscopy. Electronic properties such as HOMO and LUMO energies were derived.

  13. The Conjugation Stress of Ligand via Metal Core as the Cause of Changes in the Reactivity of Coordinated 1-Hetero-1,3-Dienes

    Directory of Open Access Journals (Sweden)

    A.I. Kuramshin

    2016-06-01

    Full Text Available Using quantum-chemical calculations carried out for interpretation of the experimentally discovered reactivity of 1-hetero-1,3-dienes that are mono- and bidentally coordinated with the transition metal core, we have revealed that the difference in hydrophosphorylation directions of the free organic molecule and the same molecule involved in the coordination sphere of the transition metal can be explained by either weakening or complete loss of conjugation between the C=C and C=X fragments as a result of coordination. In the case of monodentate coordination of heterodiene with the transition metal according to the eta(2(C,C-type, the conjugation weakening is suggested to be maximum for the transition metal characterized by the minimum electronegativity, which predetermines the increased contribution of the metalcyclopropane resonance structure into the general bonding mode. Organometallic compounds having the heterodiene ligand bidentally coordinated demonstrate the conjugation weakening parallel to the metal radius.

  14. Synthesis and crystal structure of Cu(II and Co(II complexes with 1,3-dimethyl-pyrazole-5-carboxylic acid ligand

    Directory of Open Access Journals (Sweden)

    Jaćimović Željko K.

    2015-01-01

    Full Text Available In the reaction of 1,3-dimethyl-pyrazole-5-carboxylic acid (HL with M(OAc2•4H2O, (M = Cu, Co two novel complexes have been prepared, square-planar [CuL2(H2O2] and octahedral [CoL2(MeOH4]. The crystal structures have been determined by single-crystal X-ray diffraction. In both complexes the deprotonated acid displays monodentate coordination to the metal ions. According to the results of CSD survey this is the first structural report on the metal complexes with N1-substituted pyrazole-5-carboxylic ligand. [Projekat Ministarstva nauke Republike Srbije, br. 172014 i br. 172035

  15. Imidazoline receptors ligands

    Directory of Open Access Journals (Sweden)

    Agbaba Danica

    2012-01-01

    Full Text Available Extensive biochemical and pharmacological studies have determined three different subtypes of imidazoline receptors: I1-imidazoline receptors (I1-IR involved in central inhibition of sympathicus that produce hypotensive effect; I2-imidazoline receptors (I2-IR modulate monoamine oxidase B activity (MAO-B; I3-imidazoline receptors (I3-IR regulate insulin secretion from pancreatic β-cells. Therefore, the I1/I2/I3 imidazoline receptors are selected as new, interesting targets for drug design and discovery. Novel selective I1/I2/I3 agonists and antagonists have been recently developed. In the present review, we provide a brief update to the field of imidazoline research, highlighting some of the chemical diversity and progress made in the 2D-QSAR, 3D-QSAR and quantitative pharmacophore development studies of I1-IR and I2-IR imidazoline receptor ligands. Theoretical studies of I3-IR ligands are not yet performed because of insufficient number of synthesized I3-IR ligands.

  16. Synthesis, characterization and crystal structure of four new asymmetric triazene ligands: An example of linear HII complex with H... secondary bonding interactions

    Indian Academy of Sciences (India)

    Mohammad Reza Melardi; Fatemeh Baber Shamsi Mogoii; Ayoob Babaii Sajirani; Jafar Attar Gharamaleki; Behrouz Notash; Mohammad Kazem Rofouei

    2015-12-01

    In this work, the asymmetric ligands [1-(phenyl)-3-(2-nitro-4-methylphenyl)]triazene (1), [1-(4-methylphenyl)-3-(2-nitro-4-methylphenyl)]triazene (2), [1-(4-ethylphenyl)-3-(2-nitro-4-methylphenyl)]triazene (3) and [1-(4-ethoxyphenyl)-3-(2-nitro-4-methylphenyl)]triazene (4), were synthesized. The reaction of the ligand (3) with HgCl2 in methanol resulted in the formation of the [HgL2] complex, (5). All compounds were characterized by means of CHN analysis, FT-IR, 1H NMR, 13C NMR spectroscopy. In addition, the crystal structures of the ligands (2) to (4) were investigated by single crystal X-ray analysis. In the solid state, all ligands exhibited trans conformation about the –N=N– double bond. The HgII complex (5) crystallized in monoclinic system with 2/ space group. The triazene ligand was found to be deprotonated prior to coordination and acts as monodentate ligand. The HgII which lies on inversion center (site symmetry $\\bar{1}$), is surrounded by two N atoms from L ligands forming a linear geometry. The other two Hg–N bonds are relatively longer and can only be regarded as weak secondary bonds. Also, Hg-3-arene -interactions are present in this compound. Hydrogen bonds, · · · and C–H· · · stacking interactions help in the stabilization of the resulted frameworks. These C–H· · · edge-to-face interactions are present with H· · · distance of 3.00 Å.

  17. Polymeric networks of copper(II) phenylmalonate with heteroaromatic n-donor ligands: synthesis, crystal structure, and magnetic properties.

    Science.gov (United States)

    Pasán, Jorge; Sanchiz, Joaquín; Ruiz-Pérez, Catalina; Lloret, Francesc; Julve, Miguel

    2005-10-31

    Two new phenylmalonate-bridged copper(II) complexes with the formulas [Cu(4,4'-bpy)(Phmal)](n).2nH(2)O (1) and [Cu(2,4'-bpy)(Phmal)(H(2)O)](n)() (2) (Phmal = phenylmalonate dianion, 4,4'-bpy = 4,4'-bipyridine, 2,4'-bpy = 2,4'-bipyridine) have been synthesized and characterized by X-ray diffraction. Complex 1 crystallizes in monoclinic space group P2(1), Z = 4, with unit cell parameters of a = 9.0837(6) Angstroms, b = 9.3514(4) Angstroms, c = 11.0831(8) Angstroms, and beta = 107.807(6) degrees , whereas complex 2 crystallizes in orthorhombic space group C2cb, Z = 8, with unit cell parameters of a = 10.1579(7) Angstroms, b = 10.3640(8) Angstroms, and c = 33.313(4) Angstroms. The structures of 1 and 2 consist of layers of copper(II) ions with bridging bis-monodentate phenylmalonate (1 and 2) and 4,4'-bpy (1) ligands and terminal monodentate 2,4'-bpy (2) groups. Each layer in 1 contains rectangles with dimensions of 11.08 x 4.99 Angstroms(2), the edges being defined by the Phmal and 4,4'-bpy ligands. The intralayer copper-copper separations in 1 through the anti-syn equatorial-apical carboxylate-bridge and the 4,4'-bpy molecule are 4.9922(4) and 11.083(1) Angstroms, respectively. The anti-syn equatorial-equatorial carboxylate bridge links the copper(II) atoms in complex 2 within each layer with a mean copper-copper separation of 5.3709(8) Angstroms. The presence of 2,4'-bpy as a terminal ligand accounts for the large interlayer separation of 15.22 Angstroms. The copper(II) environment presents a static pseudo-Jahn-Teller disorder which has been studied by EPR and low-temperature X-ray diffraction. Magnetic susceptibility measurements of both compounds in the temperature range 2-290 K show the occurrence of weak antiferromagnetic [J = -0.59(1) cm(-1) (1)] and ferromagnetic [J = +0.77(1) cm(-1) (2)] interactions between the copper(II) ions. The conformation of the phenylmalonate-carboxylate bridge and other structural factors, such as the planarity of the exchange

  18. 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

  19. Mixed ligand complexation of some transition metal ions in solution and solid state: Spectral characterization, antimicrobial, antioxidant, DNA cleavage activities and molecular modeling

    Science.gov (United States)

    Shobana, Sutha; Dharmaraja, Jeyaprakash; Selvaraj, Shanmugaperumal

    2013-04-01

    Equilibrium studies of Ni(II), Cu(II) and Zn(II) mixed ligand complexes involving a primary ligand 5-fluorouracil (5-FU; A) and imidazoles viz., imidazole (him), benzimidazole (bim), histamine (hist) and L-histidine (his) as co-ligands(B) were carried out pH-metrically in aqueous medium at 310 ± 0.1 K with I = 0.15 M (NaClO4). In solution state, the stoichiometry of MABH, MAB and MAB2 species have been detected. The primary ligand(A) binds the central M(II) ions in a monodentate manner whereas him, bim, hist and his co-ligands(B) bind in mono, mono, bi and tridentate modes respectively. The calculated Δ log K, log X and log X' values indicate higher stability of the mixed ligand complexes in comparison to binary species. Stability of the mixed ligand complex equilibria follows the Irving-Williams order of stability. In vitro biological evaluations of the free ligand(A) and their metal complexes by well diffusion technique show moderate activities against common bacterial and fungal strains. Oxidative cleavage interaction of ligand(A) and their copper complexes with CT DNA is also studied by gel electrophoresis method in the presence of oxidant. In vitro antioxidant evaluations of the primary ligand(A), CuA and CuAB complexes by DPPH free radical scavenging model were carried out. In solid, the MAB type of M(II)sbnd 5-FU(A)sbnd his(B) complexes were isolated and characterized by various physico-chemical and spectral techniques. Both the magnetic susceptibility and electronic spectral analysis suggest distorted octahedral geometry. Thermal studies on the synthesized mixed ligand complexes show loss of coordinated water molecule in the first step followed by decomposition of the organic residues subsequently. XRD and SEM analysis suggest that the microcrystalline nature and homogeneous morphology of MAB complexes. Further, the 3D molecular modeling and analysis for the mixed ligand MAB complexes have also been carried out.

  20. A novel three-dimensional Zn(II) coordination polymer with 1,3,5-tris(imidazol-1-ylmethyl)benzene and cyclohexane-1,3,5-tricarboxylate ligands.

    Science.gov (United States)

    Zhong, Kai-Long

    2014-02-01

    In the Zn(II) compound poly[[bis(μ3-cyclohexane-1,3,5-tricarboxylato)bis[μ3-1,3,5-tris(imidazol-1-ylmethyl)benzene]trizinc(II)] hexahydrate], {[Zn3(C18H18N6)2(C9H9O6)2]·6H2O}n, based on mixed 1,3,5-tris(imidazol-1-ylmethyl)benzene and cyclohexane-1,3,5-tricarboxylate ligands, there are two types of crystallographically independent Zn(II) centres, one in a general position and one on a crystallographic twofold axis. They have similar fourfold distorted tetrahedral coordination geometries, ligated by two monodentate carboxylate groups from two cyclohexane-1,3,5-tricarboxylate ligands and by two N atoms from two 1,3,5-tris(imidazol-1-ylmethyl)benzene ligands. The cyclohexane-1,3,5-tricarboxylate anions link the Zn(II) cations to generate a two-dimensional layered metal-organic structure running parallel to the (201) plane. Adjacent layers are further connected by tripodal 1,3,5-tris(imidazol-1-ylmethyl)benzene ligands, resulting in a three-dimensional network. The solvent water molecules are linked to the cyclohexane-1,3,5-tricarboxylate ligands via water-carboxylate O-H···O hydrogen bonds.

  1. Trivalent lanthanide compounds with fluorinated thiolate ligands: Ln-F dative interactions vary with Ln and solvent.

    Science.gov (United States)

    Melman, Jonathan H; Rohde, Christa; Emge, Thomas J; Brennan, John G

    2002-01-14

    The fluorinated tris-thiolate compounds Ln(SC(6)F(5))(3) can be isolated as THF, pyridine, or DME coordination complexes. In THF, the larger Ce forms dimeric [(THF)(3)Ce(SC(6)F(5))(3)](2) (1) with bridging thiolate ligands, while the smaller lanthanides (Ln = Ho (2), Er (3)) form monometallic (THF)(3)Ln(SC(6)F(5))(3) compounds. There is a tendency for fluoride to coordinate to Ln throughout the lanthanide series (Ce-Er). The cerium compound 1 contains a pair of bridging thiolates connecting two eight-coordinate Ce(III) ions. Of the two terminal thiolates, only one exhibits a distinct Ce-F bond. In contrast, the Ho derivative (THF)(3)Ho(SC(6)F(5))(3) is a molecular compound in the solid state, with two monodentate thiolates and one thiolate that again coordinates through both S and F atoms. Incorporation of a stronger Lewis base reduces but does not necessarily eliminate the tendency to form Ln-F bonds. Structural characterization of the eight-coordinate (pyridine)(4)Sm(SC(6)F(5))(3) (4) reveals a single, clearly defined Ln-F interaction, while in (pyridine)(4)Yb(SC(6)F(5))(3) (5) there are no Yb-F bonds. In the structure of (DME)(2)Er(SC(6)F(5))(3) (6) the DME ligands completely displace F from the Er coordination sphere.

  2. Photochemistry of RuII 4,4'-bi-1,2,3-triazolyl (btz) complexes: crystallographic characterization of the photoreactive ligand-loss intermediate trans-[Ru(bpy)(κ2-btz)(κ1-btz)(NCMe)]2+.

    Science.gov (United States)

    Welby, Christine E; Armitage, Georgina K; Bartley, Harry; Wilkinson, Aaron; Sinopoli, Alessandro; Uppal, Baljinder S; Rice, Craig R; Elliott, Paul I P

    2014-07-01

    We report the unprecedented observation and unequivocal crystallographic characterization of the meta-stable ligand loss intermediate solvento complex trans-[Ru(bpy)(κ(2) -btz)(κ(1) -btz)(NCMe)](2+) (1 a) that contains a monodentate chelate ligand. This and analogous complexes can be observed during the photolysis reactions of a family of complexes of the form [Ru({NN})(btz)(2)](2+) (1 a-d: btz=1,1'-dibenzyl-4,4'-bi-1,2,3-triazolyl; {NN}=a) 2,2'-bipyridyl (bpy), b) 4,4'-dimethyl-2,2'-bipyridyl (dmbpy), c) 4,4'-dimethoxy-2,2'-bipyridyl (dmeobpy), d) 1,10-phenanthroline (phen)). In acetonitrile solutions, 1 a-d eventually convert to the bis-solvento complexes trans-[Ru({NN})(btz)(NCMe)(2)](2+) (3 a-d) along with one equivalent of free btz, in a process in which the remaining coordinated bidentate ligands undergo a new rearrangement such that they become coplanar. X-ray crystal structure of 3 a and 3 d confirmed the co-planar arrangement of the {NN} and btz ligands and the trans coordination of two solvent molecules. These conversions proceed via the observed intermediate complexes 2 a-d, which are formed quantitatively from 1 a-d in a matter of minutes and to which they slowly revert back on being left to stand in the dark over several days. The remarkably long lifetime of the intermediate complexes (>12 h at 40 °C) allowed the isolation of 2 a in the solid state, and the complex to be crystallographically characterized. Similarly to the structures adopted by complexes 3 a and d, the bpy and κ(2) -btz ligands in 2 a coordinate in a square-planar fashion with the second monodentate btz ligand coordinated trans to an acetonitrile ligand.

  3. 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.

  4. Tropolone as anionic and neutral ligand in lead(II) and bismuth(III) complexes: Synthesis, structure, characterization and computational studies

    Science.gov (United States)

    Lyczko, Krzysztof

    2017-01-01

    Two new metal complexes, [Bi(trop)2(Htrop)(CF3SO3)] (1) and [Pb(trop)2(Htrop)] (2), have been synthesized by reaction of the respective metal triflates with an excess of tropolone (Htrop) in the concentrated methanol or dimethylsulfoxide solution. In addition, it was found that complex 1 crystallizes through the formation of unstable intermediate methanol solvated tris(tropolonato)bismuth(III) compound. The characteristic behavior of tropolone which coordinates both as the bidentate anion (trop-) and the monodentate neutral molecule (Htrop) has been revealed in 1 and 2. The crystal structures of studied compounds have been determined by single-crystal X-ray diffraction. The molecular structures of both complexes have been compared with their geometries received from DFT calculations giving a good correlation. The presented compounds show coordination number of metal ion equal to five in 2 and six in 1 and the presence of stereochemically active 6s2 lone electron pair. The complexes were characterized by FT-IR, NMR and UV-Vis techniques. IR and UV-Vis spectra of 1 and 2 were also simulated by DFT methods. TD-DFT predictions demonstrate the frontier HOMOs and LUMOs cover in the major part the tropolonate and(or) tropolone moieties which gives mainly ligand-to-ligand charge transfer (LLCT) and ligand centered (LC) character to the energy bands above 300 nm.

  5. Template Synthesis, Characterization and Biological Activity of Cu(II, Ni(II, Co(II, Zn(IIComplexes with Isonicotinoylhydrazone--2-aldehydefluorene Ligand

    Directory of Open Access Journals (Sweden)

    2010-01-01

    Full Text Available This is about synthesizing new complex combinations of Cu(II, Ni(II,Co(II, Zn(II with aroylhydrazone ligand isonicotinoylhydrazone-2-aldehydefluorene (INHAF made by condensation of isonicotinoylhydrazine with 2-aldehydefluorene. The complexes have been characterized by analytical data, IR, UV-Vis, NMR spectra, magnetic susceptibility values, thermal analysis and for the Cu(II complex the ESR spectrum has been registered. For all complexes the biological activity against the Staphylo-coccus aureus, Escherichia coli, Klebssiella pneumoniae bacteria has been investigated. The experimental data sustain stoichiometry of 1:2 (metal/ligand for the Cu(II, Ni(II, Zn(II complexes and of 1:1 for the complex with Co(II. The electronic spectra and the magnetic moments suggest octahedral stereochemistry at the complexes with Cu(II, Ni(II and the tetrahedral geometry for the Co(II complex. The INHAF ligand is coordinated bidentate by the O=C amide oxygen and the azomethine nitrogen in the complexes of Cu(II, Ni(II, Co(II and monodentate by the azomethine nitrogen in the complex of Zn(II.

  6. Further Insight into the Lability of MeCN Ligands of Cytotoxic Cycloruthenated Compounds: Evidence for the Antisymbiotic Effect Trans to the Carbon Atom at the Ru Center.

    Science.gov (United States)

    Barbosa, Ana Soraya Lima; Werlé, Christophe; Colunga, Claudia Olivia Oliva; Rodríguez, Cecilia Franco; Toscano, Ruben Alfredo; Le Lagadec, Ronan; Pfeffer, Michel

    2015-08-03

    The two MeCN ligands in [Ru(2-C6H4-2'-Py-κC,N)(Phen, trans-C)(MeCN)2]PF6 (1), both trans to a sp(2) hybridized N atom, cannot be substituted by any other ligand. In contrast, the isomerized derivative [Ru(2-C6H4-2'-Py-κC,N)(Phen, cis-C)(MeCN)2]PF6 (2), in which one MeCN ligand is now trans to the C atom of the phenyl ring orthometalated to Ru, leads to fast and quantitative substitution reactions with several monodentate ligands. With PPh3, 2 affords [Ru(2-C6H4-2'-Py-κC,N)(Phen, cis-C)(PPh3)(MeCN)]PF6 (3), in which PPh3 is trans to the C σ bound to Ru. Compound 3 is not kinetically stable, because, under thermodynamic control, it leads to 4, in which the PPh3 is trans to a N atom of the Phen ligand. Dimethylsulfoxide (DMSO) can also substitute a MeCN ligand in 2, leading to 5, in which DMSO is coordinated to Ru via its S atom trans to the N atom of the Phen ligand, the isomer under thermodynamic control being the only compound observed. We also found evidence for the fast to very fast substitution of MeCN in 2 by water or a chloride anion by studying the electronic spectra of 2 in the presence of water or NBu4Cl, respectively. An isomerization related to that observed between 3 and 4 is also found for the known monophosphine derivative [Ru(2-C6H4-2'-Py-κC,N)(PPh3, trans-C)(MeCN)3]PF6 (10), in which the PPh3 is located trans to the C of the cyclometalated 2-phenylpyridine, since, upon treatment by refluxing MeCN, it leads to its isomer 11, [Ru(2-C6H4-2'-Py-κC,N)(PPh3, cis-C)(MeCN)3]PF6. Further substitutions are also observed on 11, whereby N^N chelates (N^N = 2,2'-bipyridine and phenanthroline) substitute two MeCN ligands, affording [Ru(2-C6H4-2'-Py-κC,N)(PPh3, cis-C)(N^N)(MeCN)]PF6 (12a and 12b). Altogether, the behavior of the obtained complexes by ligand substitution reactions can be rationalized by an antisymbiotic effect on the Ru center, trans to the C atom of the cyclometalated unit, leading to compounds having the least nucleophilic ligand trans to C

  7. Macrocyclic G-quadruplex ligands

    DEFF Research Database (Denmark)

    Nielsen, M C; Ulven, Trond

    2010-01-01

    G-quadruplex stabilizing compounds have recently received increased interest due to their potential application as anticancer therapeutics. A significant number of structurally diverse G-quadruplex ligands have been developed. Some of the most potent and selective ligands currently known are macr...

  8. Photochemistry of RuII 4,4′-Bi-1,2,3-triazolyl (btz) Complexes: Crystallographic Characterization of the Photoreactive Ligand-Loss Intermediate trans-[Ru(bpy)(κ2-btz)(κ1-btz)(NCMe)]2+

    OpenAIRE

    Welby, Christine E.; Armitage, Georgina K.; Bartley, Harry; Wilkinson, Aaron; Sinopoli, Alessandro; Uppal, Baljinder S; Rice, Craig R.; Elliott, Paul I.

    2014-01-01

    We report the unprecedented observation and unequivocal crystallographic characterization of the meta-stable ligand loss intermediate solvento complex trans-[Ru(bpy)(κ2-btz)(κ1-btz)(NCMe)]2+ (1 a) that contains a monodentate chelate ligand. This and analogous complexes can be observed during the photolysis reactions of a family of complexes of the form [Ru(equation image)(btz)2]2+ (1 a–d: btz=1,1′-dibenzyl-4,4′-bi-1,2,3-triazolyl; equation image=a) 2,2′-bipyridyl (bpy), b) 4,4′-dimethyl-2,2′-...

  9. 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......-ray crystallographic analyses, chemical correlation, and CD spectral analyses. The effects of the individual stereoisomers at ionotropic and metabotropic (S)-Glu receptors (iGluRs and mGluRs) were characterized. Compounds with S-configuration at the alpha-carbon generally showed mGluR2 agonist activity of similar...... limited effect on pharmacology. Structure-activity relationships at iGluRs in the rat cortical wedge preparation showed a complex pattern, some compounds being NMDA receptor agonists [e.g., EC(50) =110 microM for (2S,5RS)-5-methyl-AA (6a,b)] and some compounds showing NMDA receptor antagonist effects [e...

  10. Construction of metal-organic frameworks through coordination and hydrogen bonding interactions: Syntheses, structures and photoluminescent properties of metal complexes with macrocyclic ligand

    Science.gov (United States)

    Ouyang, Xing-Mei; Li, Zhen-Wu; Okamura, Taka-aki; Li, Yi-Zhi; Sun, Wei-Yin; Tang, Wen-Xia; Ueyama, Norikazu

    2004-01-01

    A macrocyclic ligand L with two diethylenetriamine units linked by two rigid biphenylene spacers was used as building block for construction of metal-organic frameworks. A silver(I) complex with macrocyclic and open-chain mix-type ligands [Ag 2( L)( L')](ClO 4) 2 ( 1) [ L'=1,6-bis(4-imidazol-1'-ylmethylphenyl)-2,5-diazahexane] was obtained by reaction of L and L' together with AgClO 4·H 2O. It is interesting that the open-chain tetradentate ligand L' only served as a bidentate ligand to bridge the Ag 2L units into an infinite one-dimensional (1D) cationic chain. Neutral 1D chain coordination polymer [Cu 2( L)( μ-SO 4) 2]·3H 2O·3MeOH ( 2) is formed by sulfate bridges between the neighboring Cu 2L units. When L reacted with nickel(II) sulfate instead of copper(II) sulfate, a monomacrocycle molecular complex [Ni 2( L)(H 2O) 4(SO 4) 2] ( 3) was obtained in which the sulfate anion acts as monodentate ligands rather than as bridges. When Cd(II) salts were used for the reactions with L, another two neutral 1D coordination polymers, [Cd 2( L)( μ-Cl) 2Cl 2]·2H 2O ( 4) and [Cd 2( L)( μ-Br) 2Br 2] ( 5), with the same structure were isolated. All the synthesized complexes exhibit three-dimensional framework structures linked by various hydrogen bonds. The photoluminescent properties of the synthesized complexes were studied in the solid state at room temperature, and the Ag(I) and Cd(II) complexes were found to show strong blue luminescence.

  11. Synthesis, structure, fluorescent property, and antibacterial activity of new Cd(II) metal complex based on multidentate Schiff base ligand N,N‧-Bis(3-methoxysalicylidenimino)-1,3-diaminopropane

    Science.gov (United States)

    Majumdar, Dhrubajyoti; Das, Sourav; Biswas, Jayanta Kumar; Mondal, Monojit

    2017-04-01

    The sequential reaction of a multisite coordinating compartmental ligand N,N‧-Bis(3-methoxysalicylidenimino)-1,3-diaminopropane (H2L1) with Cd(OAc)2 followed by the addition of NaCl in a 2:3:2 stoichiometric ratio affords homometallic trinuclear Cd(II) coordination compound [Cd3(L1)2(Cl)2] (1). The complex 1 has been thoroughly characterized by common elemental analysis (CHN), FT-IR and UV-Vis spectroscopy. Single crystal X-ray diffraction was also performed to determine the complete structure of complex 1. X-ray diffraction studies reveal that the molecular complex comprises a linear tri-nuclear ensemble of cadmium metal ions, which is further supported by the concerted coordination action of two dianionic [L1]2- ligands along with two monodentate Cl- ligands. The central Cd(II) ion is attached to the terminal Cd(II) ions through two phenoxide bridging groups of the fully deprotonated ligands [L1]2-. This arrangement leads to two neighbouring four membered Cd2O2 rings. The terminal Cd(II) ions are penta-coordinated (2 N, 2O, Cl) in a distorted square pyramidal geometry and central Cd(II) ion attained distorted trigonal prismatic geometry through six oxygen atoms coordination from ligands. Tri-nuclear Cd(II) complex 1 display intraligand (π-π∗) fluorescence in DMSO solution at room temperature. The fluorescence properties of complex 1 as well as the respective di-compartmental Schiff base ligand (H2L1) have been investigated in DMSO solvent at room temperature with a comparative approach. Result confirmed that complex 1 is highly fluorescence active mediated due to "chelation enhanced fluorescence" [CHEF] but Schiff base ligand (H2L1) is fluorescence silent. The antibacterial efficacy of complex 1 was further investigated against some important Gram-positive and Gram-negative bacteria.

  12. Visualization of Metal-to-Ligand and Ligand-to-Ligand Charge Transfer in Metal-Ligand Complexes

    Institute of Scientific and Technical Information of China (English)

    Yong Ding; Jian-xiu Guo; Xiang-si Wang; Sha-sha Liu; Feng-cai Ma

    2009-01-01

    Three methods including the atomic resolved density of state, charge difference density, and the transition density matrix are used to visualize metal to ligand charge transfer (MLCT) in ruthenium(Ⅱ) ammine complex. The atomic resolved density of state shows that there is density of Ru on the HOMOs. All the density is localized on the ammine, which reveals that the excited electrons in the Ru complex are delocalized over the ammine ligand. The charge difference density shows that all the holes are localized on the Ru and the electrons on the ammine. The localization explains the MLCT on excitation. The transition density matrix shows that there is electron-hole coherence between Ru and ammine. These methods are also used to examine the MLCT in Os(bpy)(p0p)Cl ("Osp0p"; bpy=2,2'-bipyridyl; p0p=4,4'-bipyridyl) and the ligand-to-ligand charge transfer (LLCT) in Alq3. The calculated results show that these methods are powerful to examine MLCT and LLCT in the metal-ligand system.

  13. Monofunctional platinum(II) complexes with potent tumor cell growth inhibitory activity: the effect of a hydrogen-bond donor/acceptor N-heterocyclic ligand.

    Science.gov (United States)

    Margiotta, Nicola; Savino, Salvatore; Gandin, Valentina; Marzano, Christine; Natile, Giovanni

    2014-06-01

    In this paper we investigate the possibility of further increase the role of the N-donor aromatic base in antitumor Hollis-type compounds by conferring the possibility to act as a hydrogen-bond donor/acceptor. Therefore, we synthesized the Pt(II) complex cis-[PtCl(NH3 )2 (naph)]NO3 (1) containing the 1,8-naphthyridine (naph) ligand. The naphthyridine ligand is generally monodentate, and the second nitrogen atom can act as H-bond donor/acceptor depending upon its protonation state. The possibility of forming such an H-bond could be crucial in the interaction of the drug with DNA or proteins. Apart from the synthesis of the compound, in this study we evaluated its in vitro antitumor activity in a wide panel of tumor cell lines, also including cells selected for their sensitivity/resistance to oxaliplatin, which was compared with that of previously reported complex 2 ([PtI(2,9-dimethyl-1,10-phenanthroline)(1-methyl-cytosine)]I) and oxaliplatin and cisplatin as reference compounds. The cytotoxicity data were correlated with the cellular uptake and the DNA platination levels. Finally, the reactivity of 1 towards guanosine 5'-monophosphate (5'-GMP) and glutathione was investigated to provide insights into its mechanism of action.

  14. Crystal structures of two ansa-titanocene tri-fluoro-methane-sulfonate complexes bearing the Me2Si(C5Me4)2 ligand.

    Science.gov (United States)

    Kessler, Monty; Godemann, Christian; Spannenberg, Anke; Beweries, Torsten

    2016-12-01

    The crystal structures of two ansa-titanocene tri-fluoro-methane-sulfonate complexes bearing the Me2Si(C5Me4)2 ligand are reported, namely [di-methylbis-(η(5)-tetra-methyl-cyclo-penta-dien-yl)silane](tri-fluoro-methane-sulfonato-κ(2)O,O')titanium(III) toluene monosolvate, [Ti(CF3O3S)(C20H30Si)]·C7H8, 1, and chlorido-[di-methyl-bis-(η(5)-tetra-methyl-cyclo-penta-dien-yl)silane](tri-fluoro-methane-sulfonato-κO)titanium(IV), [Ti(CF3O3S)(C20H30Si)Cl], 2. Both complexes display a bent metallocene unit, the metal atom being coordinated in a distorted tetra-hedral geometry, with the tri-fluoro-methane-sulfonate anion acting as a bidentate or monodentate ligand in 1 and 2, respectively. In 1, weak π-π stacking inter-actions involving the toluene solvent mol-ecules [centroid-to-centroid distance = 3.9491 (11) Å] are observed.

  15. Molecular Recognition and Ligand Association

    Science.gov (United States)

    Baron, Riccardo; McCammon, J. Andrew

    2013-04-01

    We review recent developments in our understanding of molecular recognition and ligand association, focusing on two major viewpoints: (a) studies that highlight new physical insight into the molecular recognition process and the driving forces determining thermodynamic signatures of binding and (b) recent methodological advances in applications to protein-ligand binding. In particular, we highlight the challenges posed by compensating enthalpic and entropic terms, competing solute and solvent contributions, and the relevance of complex configurational ensembles comprising multiple protein, ligand, and solvent intermediate states. As more complete physics is taken into account, computational approaches increase their ability to complement experimental measurements, by providing a microscopic, dynamic view of ensemble-averaged experimental observables. Physics-based approaches are increasingly expanding their power in pharmacology applications.

  16. Why mercury prefers soft ligands

    Energy Technology Data Exchange (ETDEWEB)

    Riccardi, Demian M [ORNL; Guo, Hao-Bo [ORNL; Gu, Baohua [ORNL; Parks, Jerry M [ORNL; Summers, Anne [University of Georgia, Athens, GA; Miller, S [University of California, San Francisco; Liang, Liyuan [ORNL; Smith, Jeremy C [ORNL

    2013-01-01

    Mercury (Hg) is a major global pollutant arising from both natural and anthropogenic sources. Defining the factors that determine the relative affinities of different ligands for the mercuric ion, Hg2+, is critical to understanding its speciation, transformation, and bioaccumulation in the environment. Here, we use quantum chemistry to dissect the relative binding free energies for a series of inorganic anion complexes of Hg2+. Comparison of Hg2+ ligand interactions in the gaseous and aqueous phases shows that differences in interactions with a few, local water molecules led to a clear periodic trend within the chalcogenide and halide groups and resulted in the well-known experimentally observed preference of Hg2+ for soft ligands such as thiols. Our approach establishes a basis for understanding Hg speciation in the biosphere.

  17. Crystal structure of a mixed-ligand dinuclear Ba-Zn complex with 2-meth-oxy-ethanol having tri-phenyl-acetate and chloride bridges.

    Science.gov (United States)

    Utko, Józef; Sobocińska, Maria; Dobrzyńska, Danuta; Lis, Tadeusz

    2015-07-01

    The dinuclear barium-zinc complex, μ-chlorido-1:2κ(2) Cl:Cl-chlorido-2κCl-bis-(2-meth-oxy-ethanol-1κO)bis-(2-meth-oxy-ethanol-1κ(2) O,O')bis-(μ-tri-phenyl-acetato-1:2κ(2) O:O')bariumzinc, [BaZn(C20H15O2)2Cl2(C3H8O2)4], has been synthesized by the reaction of barium tri-phenyl-acetate, anhydrous zinc chloride and 2-meth-oxy-ethanol in the presence of toluene. The barium and zinc metal cations in the dinuclear complex are linked via one chloride anion and carboxyl-ate O atoms of the tri-phenyl-acetate ligands, giving a Ba⋯Zn separation of 3.9335 (11) Å. The irregular nine-coordinate BaO8Cl coordination centres comprise eight O-atom donors, six of them from 2-meth-oxy-ethanol ligands (four from two bidentate O,O'-chelate inter-actions and two from monodentate inter-actions), two from bridging tri-phenyl-acetate ligands and one from a bridging Cl donor. The distorted tetra-hedral coordination sphere of zinc comprises two O-atom donors from the tri-phenyl-acetate ligands and two Cl donors (one bridging and one terminal). In the crystal, O-H⋯Cl, O-H⋯O and C-H⋯Cl inter-molecular inter-actions form a layered structure, lying parallel to (001).

  18. New Mn(II, Ni(II, Cd(II, Pb(II complexes with 2-methylbenzimidazole and other ligands. Synthesis, spectroscopic characterization, crystal structure, magnetic susceptibility and biological activity studies

    Directory of Open Access Journals (Sweden)

    Shayma A. Shaker

    2016-11-01

    Full Text Available Synthesis and characterization of Mn(II, Ni(II, Cd(II and Pb(II mixed ligand complexes of 2-methylbenzimidazole with other ligands have been reported. The structure of the ligands and their complexes was investigated using elemental analysis, IR, UV–Vis, (1H, 13C NMR spectroscopy, molar conductivity and magnetic susceptibility measurements. In all the studies of complexes, the 2-methylbenzimidazole behaves as a neutral monodentate ligand which is coordinated with the metal ions through the N atom. While benzotriazole behaves as a neutral bidentate ligand which is coordinated with the Ni(II ion through the two N atoms. Moreover, the N-acetylglycine behaves as a bidentate ligand which is coordinated with the Mn(II, Ni(II and Pb(II ions through the N atom and the terminal carboxyl oxygen atom. The magnetic and spectral data indicate the tetrahedral geometry for Mn(II complex, irregular tetrahedral geometry for Pb(II complex and octahedral geometry for Ni(II complex. The X-ray single crystal diffraction method was used to confirm a centrosymmetric dinuclear Cd(II complex as each two metal ions are linked by a pair of thiocyanate N = S bridge. Two 2-methylbenzimidazole N-atom donors and one terminal thiocyanate N atom complete a highly distorted square pyramid geometry around the Cd atom. Besides, different cell types were used to determine the inhibitory effect of Mn(II, Ni(II, Cd(II and Pb(II complexes on cell growth using MTT assay. Cd(II complex showed cytotoxic effect on various types of cancer cell lines with different EC50 values.

  19. Ligand effects on the structures and magnetic properties of tricyanomethanide-containing copper(II) complexes.

    Science.gov (United States)

    Yuste, Consuelo; Bentama, Abdeslem; Stiriba, Salah-Eddine; Armentano, Donatella; De Munno, Giovanni; Lloret, Francesc; Julve, Miguel

    2007-11-28

    nitrogen atoms from two 2,3-dpp groups [Cu(1) and Cu(2)] either two terminally bound tcm ligands [Cu(1)] or a water molecule and a monodentate tcm ligand [Cu(2)] in cis positions. Magnetic susceptibility measurements for 1-4 in the temperature range 1.9-295 K reveal the occurrence of strong [J ca.-1000 cm(-1) (1); H = -JS(A) x S(B)] and weak [J = -0.13 (2), -0.67 (3) and -0.18 cm(-1) (4); H = -J Sigma(I)S(i) x S(i+1)] antiferromagnetic interactions in agreement with the different nature of the exchange pathways involved, diazine and single mu-hydroxo (1) and the extended 2,5-dpp (2), 2,3-dpp (3) and single mu-1,5-tcm (4) bridges with copper-copper separations of 3.363(8) (1), 7.111(1) (2), 6.823(1) and 7.056(1) (3) and 7.446(1) A (4).

  20. A race for RAGE ligands.

    Science.gov (United States)

    Schleicher, Erwin D

    2010-08-01

    In experimental animals a causal involvement of the multiligand receptor for advanced glycation end products (RAGE) in the development of diabetic vascular complications has been demonstrated. However, the nature of RAGE ligands present in patients with diabetic nephropathy has not yet been defined; this leaves open the relevance of the RAGE system to the human disease.

  1. Controlled-deactivation cannabinergic ligands.

    Science.gov (United States)

    Sharma, Rishi; Nikas, Spyros P; Paronis, Carol A; Wood, Jodianne T; Halikhedkar, Aneetha; Guo, Jason Jianxin; Thakur, Ganesh A; Kulkarni, Shashank; Benchama, Othman; Raghav, Jimit Girish; Gifford, Roger S; Järbe, Torbjörn U C; Bergman, Jack; Makriyannis, Alexandros

    2013-12-27

    We report an approach for obtaining novel cannabinoid analogues with controllable deactivation and improved druggability. Our design involves the incorporation of a metabolically labile ester group at the 2'-position on a series of (-)-Δ(8)-THC analogues. We have sought to introduce benzylic substituents α to the ester group which affect the half-lives of deactivation through enzymatic activity while enhancing the affinities and efficacies of individual ligands for the CB1 and CB2 receptors. The 1'-(S)-methyl, 1'-gem-dimethyl, and 1'-cyclobutyl analogues exhibit remarkably high affinities for both CB receptors. The novel ligands are susceptible to enzymatic hydrolysis by plasma esterases in a controllable manner, while their metabolites are inactive at the CB receptors. In further in vitro and in vivo experiments key analogues were shown to be potent CB1 receptor agonists and to exhibit CB1-mediated hypothermic and analgesic effects.

  2. Privileged chiral ligands and catalysts

    CERN Document Server

    Zhou, Qi-Lin

    2011-01-01

    This ultimate ""must have"" and long awaited reference for every chemist working in the field of asymmetric catalysis starts with the core structure of the catalysts, explaining why a certain ligand or catalyst is so successful. It describes in detail the history, the basic structural characteristics, and the applications of these ""privileged catalysts"". A novel concept that gives readers a much deeper insight into the topic.

  3. Tumor targeting via integrin ligands

    Directory of Open Access Journals (Sweden)

    Udaya Kiran eMarelli

    2013-08-01

    Full Text Available Selective and targeted delivery of drugs to tumors is a major challenge for an effective cancer therapy and also to overcome the side effects associated with current treatments. Overexpression of various receptors on tumor cells is a characteristic structural and biochemical aspect of tumors and distinguishes them from physiologically normal cells. This abnormal feature is therefore suitable for selectively directing anticancer molecules to tumors by using ligands that can preferentially recognize such receptors. Several subtypes of integrin receptors that are crucial for cell adhesion, cell signaling, cell viability and motility have been shown to have an upregulated expression on cancer cells. Thus, ligands that recognize specific integrin subtypes represent excellent candidates to be conjugated to drugs or drug carrier systems and be targeted to tumors. In this regard, integrins recognizing the RGD cell adhesive sequence have been extensively targeted for tumor specific drug delivery. Here we review key recent examples on the presentation of RGD-based integrin ligands by means of distinct drug delivery systems, and discuss the prospects of such therapies to specifically target tumor cells.

  4. Two Zn(II) coordination complexes assembled by trithiocyanuric acid and two different N-donor auxiliary ligands.

    Science.gov (United States)

    He, Xiao Xiao; Guo, Ya Mei

    2014-08-01

    The dipyridyl-type building blocks 4-amino-3,5-bis(pyridin-3-yl)-1,2,4-triazole (3-bpt) and 4,4'-bipyridine (bpy) have been used to assemble with Zn(II) in the presence of trithiocyanuric acid (ttcH3) to afford two coordination compounds, namely bis[4-amino-3,5-bis(pyridin-3-yl)-1,2,4-triazole-κN(3)]bis(trithiocyanurato-κ(2)N,S)zinc(II), [Zn(C3H2N3S3)2(C12H10N6)2]·2H2O, (1), and catena-poly[[[bis(trithiocyanurato-κ(2)N,S)zinc(II)]-μ-4,4'-bipyridine-κ(2)N:N'] 4,4'-bipyridine monosolvate], {[Zn2(C3H2N3S3)4(C10H8N2)3]·C10H8N2}n, (2). Single-crystal X-ray analysis indicates that complex (1) is a mononuclear structure, while complex (2) presents a one-dimensional chain coordination motif. In both complexes, the central Zn(II) cation adopts an octahedral geometry, coordinated by four N- and two S-donor atoms. Notably, trithiocyanurate (ttcH2(-)) adopts the same bidentate chelating coordination mode in each complex and exists in the thione tautomeric form. The 3-bpt co-ligand in (1) adopts a monodentate coordination mode and serves as a terminal pendant ligand, whereas the 4,4'-bipyridine (bpy) ligand in (2) adopts a bidentate-bridging coordination mode. The different coordination characters of the different N-donor auxiliary ligands lead to structural diversity for complexes (1) and (2). Further analysis indicates that the resultant three-dimensional supramolecular networks for (1) and (2) arise through intermolecular N-H...S and N-H...N hydrogen bonds. Both complexes have been further characterized by FT-IR spectroscopy and elemental analyses.

  5. Contrasting coordination behavior of Group 12 perchlorate salts with an acyclic N3O2 donor ligand by X-ray crystallography and (1)H NMR.

    Science.gov (United States)

    Tice, Daniel B; Pike, Robert D; Bebout, Deborah C

    2016-08-09

    An unbranched N3O2 ligand 2,6-bis[((2-pyridinylmethyl)oxy)methyl]pyridine (L1) was used to prepare new mononuclear heteroleptic Group 12 perchlorate complexes characterized by IR, (1)H NMR and X-ray crystallography. Racemic complexes with pentadentate L1 and one to four oxygens from either water or perchlorate bound to a metal ion were structurally characterized. Octahedral [Zn(L1)(OH2)](ClO4)2 (1) and pentagonal bipyramidal [Cd(L1)(OH2)(OClO3)]ClO4 (2) structures were found with lighter congeners. The polymorphic forms of [Hg(L1)(ClO4)2] characterized (3 in P1[combining macron] and 4 in P21/c) had a mix of monodentate, anisobidentate and bidentate perchlorates, providing the first examples of a tricapped trigonal prismatic Hg(ii) coordination geometry, as well as additional examples of a rare square antiprismatic Hg(ii) coordination geometry. Solution state (1)H NMR characterization of the Group 12 complexes in CD3CN indicated intramolecular reorganization remained rapid under conditions where intermolecular M-L1 exchange was slow on the chemical shift time scale for Zn(ii) and on the J(M(1)H) time scale for Cd(ii) and Hg(ii). Solution studies with more than one equivalent of ligand also suggested that a complex with a 1 : 2 ratio of M : L1 contributed significantly to solution equilibria with Hg(ii) but not the other metal ions. The behavior of related linear pentadentate ligands with Group 12 perchlorate salts is discussed.

  6. XAFS studies of metal-ligand interactions at organic surfaces and in solution

    Science.gov (United States)

    Boyanov, Maxim I.

    X-ray absorption fine structure spectroscopy (XAFS) was used as a structural probe to determine the mechanism of metal adsorption to organic surfaces. Two specific systems were investigated, Pb adsorption to heneicosanoic acid Langmuir monolayers (CH3(CH2)19COOH), and Cd adsorption to isolated cell walls of the Bacillus subtilis bacterium. Although the study of these systems is important for quite different reasons, the goal in both is metal binding site speciation and structural characterization of the surface complex. The adsorption of aqueous Cd to B. subtilis was studied as a function of pH by fluorescence mode bulk XAFS. Samples were prepared at six pH values in the range 3.4 to 7.8, and the bacterial functional groups responsible for the adsorption were identified under each condition. Under the experimental Cd and bacterial concentrations, the spectroscopy results indicate that Cd binds predominantly to protonated phosphoryl ligands below pH 4.4, while at higher pH adsorption to carboxyl groups becomes increasingly important. At pH 7.8 we observe the activation of an additional binding site, which we tentatively ascribe to deprotonated phosphoryl ligands. A quantitative Cd speciation diagram for the pH range is presented. Grazing-incidence Pb L3 edge XAFS was used in situ to determine the adsorption complex structure in the Pb-Langmuir monolayer study. The results indicate covalent binding of the Pb cations to the carboxyl headgroups, and the observed Pb-Pb coordination suggests that the metal is adsorbed as a hydrolysis polymer, rather than as individual Pb 2+ ions. The data suggest a bidentate binding mechanism and a one Pb atom to one carboxyl headgroup binding stoichiometry. We discuss how this adsorption model can explain the peculiarities observed with Pb in previous metal-Langmuir monolayer studies. A systematic study of the metal local environment in aqueous solutions was conducted and used in the above analyses. Perchlorate and acetate salt

  7. Pseudohalide copper(II) complexes derived from polypyridyl ligands: Synthesis and characterization

    Science.gov (United States)

    Mautner, Franz A.; Louka, Febee R.; LeGuet, Thibaut; Massoud, Salah S.

    2009-02-01

    A novel series of pseudohalide- ( N3- NCS -) and perchlorato-Cu(II) complexes possessing a series of ligands with pyridyl-containing donors have been investigated. These include [Cu(pmap)ClO 4)]ClO 4 ( 1), [Cu(pmap)(N 3)]ClO 4 ( 2), [Cu(pmea)(N 3)]ClO 4·H 2O ( 3), [Cu(dp-pa)(N 3)]ClO 4·½H 2O ( 4), [Cu(pzdepy)ClO 4]ClO 4 ( 5), [Cu(pzdepy)(NCS)]ClO 4 ( 6) and [Cu 2(L)(NCS) 4]·2CH 3CN ( 7) where pmap = bis[2-(2-pyridylethyl)]-(2-pyridylmethyl)amine, pmea = bis(2-pyridylmethyl)-2-(2-pyridylethyl)amine, dp-pa = N-propanamide- N, N-bis(2-pyridylmethyl)amine, pzdepy = N, N'-bis[2-(2-pyridylethyl)]piperazine and L = 3,5-bis[bis(2-pyridylmethyl)aminomethyl]-toluene. All complexes were characterized by elemental analyses, IR and UV-Visible spectroscopy. The visible spectra of all complexes reveal the square-pyramidal geometries (SP) around the central Cu 2+ ion. IR spectra confirmed the coordination of the ClO4- group in 1 and 5 and the N-donor thiocyanate group in complexes 6 and 7. The X-ray structure determination of the pseudohalide complexes 2, 6 and 7 confirmed the monodentate coordination nature of N3- and NCS - ions. The structure of 2 or 6 consists of isolated [Cu(pmap)(N 3)] + or [Cu(pzdepy)(NCS)] + cations and perchlorate counter anions. The copper centers are penta-coordinated by the four N atoms of the pmap or pzdepy and N(5) atom of the azide group in 2 and the thiocyanate group in 6. In the dinuclear unit [Cu 2(L)(NCS) 4] of 7, each copper atom forms bonds to three nitrogen atoms of the ligand L, [Cu sbnd N bonds from 2.013(2) to 2.054(2) Å], and to N(4) and N(5) atoms of the two terminal thiocyanato groups [Cu(1) sbnd N(4) = 1.954(2) Å; Cu(1) sbnd N(5) = 2.178(2) Å]. The intradimer Cu(1)...Cu(1A) distance is 5.7010(14) Å. An intramolecular π-π stacking with a ring-ring separation of 3.5991(14) Å is observed between the central benzene ring and the pyridyl rings. In the three complexes ( 2, 6 and 7), the CuN 5 chromophore may be described as an

  8. [μ-Bis(diphenyl-arsino)methane-1:2κAs:As']nona-carbonyl-1κC,2κC,3κC-[diphen-yl(phenyl-sulfanylmeth-yl)phosphine-3κP]-triangulo-triruthenium(0) chloro-form hemisolvate.

    Science.gov (United States)

    Shawkataly, Omar Bin; Khan, Imthyaz Ahmed; Yeap, Chin Sing; Fun, Hoong-Kun

    2010-01-30

    The asymmetric unit of the title triangulo-triruthenium cluster, [Ru(3)(C(25)H(22)As(2))(C(19)H(17)PS)(CO)(9)]·0.5CHCl(3), contains of one mol-ecule of the triangulo-triruthenium complex and half a mol-ecule of the disordered (two positions of equal weight) chloro-form solvent. The bis-(diphenyl-arsino)methane ligand bridges an Ru-Ru bond and the monodentate phosphine ligand bonds to the third Ru atom. Both the arsine and phosphine ligands are equatorial with respect to the Ru(3) triangle. In addition, each Ru atom carries one equatorial and two axial terminal carbonyl ligands. The benzene ring of phenyl-thio-methyl is disordered over two positions with refined site occupancies of 0.788 (11) and 0.212 (11). In the crystal packing, mol-ecules are linked into chains along b axis by inter-molecular C-H⋯O hydrogen bonds. Weak inter-molecular C-H⋯π inter-actions further stabilize the crystal structure.

  9. [μ-Bis(diphenyl-arsino)methane-1:2κAs:As'][(4-bromo-phen-yl)diphenyl-phosphine-3κP]nona-carbonyl-1κC,2κC,3κC-triangulo-tri-ruthenium(0) chloro-form 0.3-solvate.

    Science.gov (United States)

    Shawkataly, Omar Bin; Khan, Imthyaz Ahmed; Yeap, Chin Sing; Fun, Hoong-Kun

    2010-01-16

    The asymmetric unit of the title triangulo-triruthenium compound, [Ru(3)(C(25)H(22)As(2))(C(18)H(14)BrP)(CO)(9)]·0.3CHCl(3), contains one mol-ecule of the triangulo-triruthenium complex and one partially occupied disordered chloro-form solvent mol-ecule. The bis-(diphenyl-arsino)methane ligand bridges an Ru-Ru bond and the monodentate phosphine ligand bonds to the third Ru atom. Both the arsine and phosphine ligands are equatorial with respect to the Ru(3) triangle. In addition, each Ru atom carries one equatorial and two axial terminal carbonyl ligands. The phosphine-substituted benzene rings make dihedral angles of 67.5 (3), 76.1 (3) and 78.1 (3)° with each other. The dihedral angles between the two benzene rings are 79.0 (4) and 81.4 (3)° for the two diphenyl-arsino groups. In the crystal packing, the mol-ecules are linked into chains along the a axis by inter-molecular C-H⋯O hydrogen bonds.

  10. [μ-Bis(diphenyl-arsino)methane-1:2κAs:As']nona-carbonyl-1κC,2κC,3κC-[(penta-fluoro-phen-yl)diphenyl-phosphine-3κP]-triangulo-triruthenium(0) chloro-form monosolvate.

    Science.gov (United States)

    Shawkataly, Omar Bin; Khan, Imthyaz Ahmed; Yeap, Chin Sing; Fun, Hoong-Kun

    2010-01-16

    The asymmetric unit of the title triangulo-triruthenium compound, [Ru(3)(C(25)H(22)As(2))(C(18)H(10)F(5)P)(CO)(9)]·CHCl(3), contains one mol-ecule of the triangulo-triruthenium complex and one mol-ecule of the disordered chloro-form solvent. The bis-(diphenyl-arsino)methane ligand bridges an Ru-Ru bond and the monodentate phosphine ligand bonds to the third Ru atom. Both the arsine and phosphine ligands are equatorial with respect to the Ru(3) triangle. In addition, each Ru atom carries one equatorial and two axial terminal carbonyl ligands. The phosphine-substituted benzene rings make dihedral angles of 68.43 (15), 65.14 (14) and 89.75 (14)° with each other. The dihedral angles between the two benzene rings are 80.70 (15) and 84.53 (16)° for the two diphenyl-arsino groups. In the crystal packing, the mol-ecules are linked into a plane parallel to bc by inter-molecular C-H⋯O and C-H⋯F hydrogen bonds. Weak inter-molecular C-H⋯π inter-actions further stabilize the crystal structure.

  11. [μ-Bis(diphenylarsinomethane-1:2κ2As:As′]nonacarbonyl-1κ3C,2κ3C,3κ3C-[tris(4-fluorophenylphosphine-3κP]-triangulo-triruthenium(0

    Directory of Open Access Journals (Sweden)

    Hoong-Kun Fun

    2009-12-01

    Full Text Available In the title triangulo-triruthenium compound, [Ru3(C25H22(As2(C18H12F3P(CO9], the bis(diphenylarsinomethane ligand bridges an Ru—Ru bond and the monodentate phosphine ligand bonds to the third Ru atom. Both the phosphine and arsine ligands are equatorial with respect to the Ru3 triangle. Additionally, each Ru atom carries one equatorial and two axial terminal carbonyl ligands. The three phosphine-substituted rings make dihedral angles of 87.76 (13, 57.43 (13 and 73.81 (12° with each other. The dihedral angles between the pairs of rings are 69.78 (14 and 83.38 (16° for the two diphenylarsino groups. In the crystal packing, molecules are linked by intermolecular C—H...F and C—H...O hydrogen bonds, forming two-dimensional planes parallel to the ab plane. These planes are also linked by intermolecular C—H...O hydrogen bonds into a three-dimensional framework. Intermolecular C—H...π interactions further stabilize the crystal structure.

  12. (Benzyldiphenylphosphine-3κP[μ-bis(diphenylarsinomethane-1:2κ2As:As′]nonacarbonyl-1κ3C,2κ3C,3κ3C-triangulo-triruthenium(0

    Directory of Open Access Journals (Sweden)

    Omar bin Shawkataly

    2010-01-01

    Full Text Available The asymmetric unit of the title triangulo-triruthenium compound, [Ru3(C25H22As2(C19H17P(CO9], consists of two crystallographically independent molecules of the triangulo-triruthenium complex, A and B. The bis(diphenylarsinomethane ligand bridges an Ru—Ru bond and the monodentate phosphine ligand bonds to the third Ru atom. Both the phosphine and arsine ligands are equatorial with respect to the Ru3 triangle. In addition, each Ru atom carries one equatorial and two axial terminal carbonyl ligands. With regard to the three phosphine-substituted rings, the benzyl ring makes dihedral angles of 41.0 (3 and 43.9 (3° with the other two benzene rings in molecule A; these angles are 49.8 (3 and 56.8 (3° in molecule B. The dihedral angles between the two benzene rings are 76.1 (3 and 88.2 (3° for the two diphenylarsino groups in molecule A and 71.3 (3 and 78.1 (3° in molecule B. In the crystal packing, molecules are linked into chains via intermolecular C—H...O hydrogen bonds. Weak intermolecular C—H...π interactions further stabilize the crystal structure.

  13. [μ-Bis(diphenylarsinomethane-1:2κ2As:As′]nonacarbonyl-1κ3C,2κ3C,3κ3C-[(pentafluorophenyldiphenylphosphine-3κP]-triangulo-triruthenium(0 chloroform monosolvate

    Directory of Open Access Journals (Sweden)

    Omar bin Shawkataly

    2010-02-01

    Full Text Available The asymmetric unit of the title triangulo-triruthenium compound, [Ru3(C25H22As2(C18H10F5P(CO9]·CHCl3, contains one molecule of the triangulo-triruthenium complex and one molecule of the disordered chloroform solvent. The bis(diphenylarsinomethane ligand bridges an Ru—Ru bond and the monodentate phosphine ligand bonds to the third Ru atom. Both the arsine and phosphine ligands are equatorial with respect to the Ru3 triangle. In addition, each Ru atom carries one equatorial and two axial terminal carbonyl ligands. The phosphine-substituted benzene rings make dihedral angles of 68.43 (15, 65.14 (14 and 89.75 (14° with each other. The dihedral angles between the two benzene rings are 80.70 (15 and 84.53 (16° for the two diphenylarsino groups. In the crystal packing, the molecules are linked into a plane parallel to bc by intermolecular C—H...O and C—H...F hydrogen bonds. Weak intermolecular C—H...π interactions further stabilize the crystal structure.

  14. [μ-Bis(diphenylarsinomethane-1:2κ2As:As′]nonacarbonyl-1κ3C,2κ3C,3κ3C-[tris(4-methylphenylphosphine-3κP]-triangulo-triruthenium(0

    Directory of Open Access Journals (Sweden)

    Omar bin Shawkataly

    2010-01-01

    Full Text Available In the title triangulo-triruthenium compound, [Ru3(C25H22As2(C21H21P(CO9], the bis(diphenylarsinomethane ligand bridges a Ru—Ru bond and the monodentate phosphine ligand bonds to the third Ru atom. Both the phosphine and arsine ligands are equatorial with respect to the Ru3 triangle. Additionally, each Ru atom carries one equatorial and two axial terminal carbonyl ligands. The three phenyl rings of the phosphine make dihedral angles of 86.89 (19, 82.1 (2 and 63.0 (2° with each other. The dihedral angles between the two phenyl rings are 73.8 (2 and 82.2 (3° for the two diphenylarsino groups. An intramolecular C—H...O hydrogen bond stabilizes the molecular structure. In the crystal packing, molecules are linked into chains down the b axis via intermolecular C—H...O hydrogen bonds.

  15. Ligand placement based on prior structures: the guided ligand-replacement method

    Energy Technology Data Exchange (ETDEWEB)

    Klei, Herbert E. [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Bristol-Myers Squibb, Princeton, NJ 08543-4000 (United States); Moriarty, Nigel W., E-mail: nwmoriarty@lbl.gov; Echols, Nathaniel [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Terwilliger, Thomas C. [Los Alamos National Laboratory, Los Alamos, NM 87545-0001 (United States); Baldwin, Eric T. [Bristol-Myers Squibb, Princeton, NJ 08543-4000 (United States); Natural Discovery LLC, Princeton, NJ 08542-0096 (United States); Pokross, Matt; Posy, Shana [Bristol-Myers Squibb, Princeton, NJ 08543-4000 (United States); Adams, Paul D. [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); University of California at Berkeley, Berkeley, CA 94720-1762 (United States)

    2014-01-01

    A new module, Guided Ligand Replacement (GLR), has been developed in Phenix to increase the ease and success rate of ligand placement when prior protein-ligand complexes are available. The process of iterative structure-based drug design involves the X-ray crystal structure determination of upwards of 100 ligands with the same general scaffold (i.e. chemotype) complexed with very similar, if not identical, protein targets. In conjunction with insights from computational models and assays, this collection of crystal structures is analyzed to improve potency, to achieve better selectivity and to reduce liabilities such as absorption, distribution, metabolism, excretion and toxicology. Current methods for modeling ligands into electron-density maps typically do not utilize information on how similar ligands bound in related structures. Even if the electron density is of sufficient quality and resolution to allow de novo placement, the process can take considerable time as the size, complexity and torsional degrees of freedom of the ligands increase. A new module, Guided Ligand Replacement (GLR), was developed in Phenix to increase the ease and success rate of ligand placement when prior protein–ligand complexes are available. At the heart of GLR is an algorithm based on graph theory that associates atoms in the target ligand with analogous atoms in the reference ligand. Based on this correspondence, a set of coordinates is generated for the target ligand. GLR is especially useful in two situations: (i) modeling a series of large, flexible, complicated or macrocyclic ligands in successive structures and (ii) modeling ligands as part of a refinement pipeline that can automatically select a reference structure. Even in those cases for which no reference structure is available, if there are multiple copies of the bound ligand per asymmetric unit GLR offers an efficient way to complete the model after the first ligand has been placed. In all of these applications, GLR

  16. CB receptor ligands from plants.

    Science.gov (United States)

    Woelkart, Karin; Salo-Ahen, Outi M H; Bauer, Rudolf

    2008-01-01

    Advances in understanding the physiology and pharmacology of the endogenous cannabinoid system have potentiated the interest of cannabinoid receptors as potential therapeutic targets. Cannabinoids have been shown to modulate a variety of immune cell functions and have therapeutic implications on central nervous system (CNS) inflammation, chronic inflammatory conditions such as arthritis, and may be therapeutically useful in treating autoimmune conditions such as multiple sclerosis. Many of these drug effects occur through cannabinoid receptor signalling mechanisms and the modulation of cytokines and other gene products. Further, endocannabinoids have been found to have many physiological and patho-physiological functions, including mood alteration and analgesia, control of energy balance, gut motility, motor and co-ordination activities, as well as alleviation of neurological, psychiatric and eating disorders. Plants offer a wide range of chemical diversity and have been a growing domain in the search for effective cannabinoid ligands. Cannabis sativa L. with the known plant cannabinoid, Delta(9-)tetrahydrocannabinol (THC) and Echinacea species with the cannabinoid (CB) receptor-binding lipophilic alkamides are the best known herbal cannabimimetics. This review focuses on the state of the art in CB ligands from plants, as well their possible therapeutic and immunomodulatory effects.

  17. 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.

  18. Measurement of protein-ligand complex formation.

    Science.gov (United States)

    Lowe, Peter N; Vaughan, Cara K; Daviter, Tina

    2013-01-01

    Experimental approaches to detect, measure, and quantify protein-ligand binding, along with their theoretical bases, are described. A range of methods for detection of protein-ligand interactions is summarized. Specific protocols are provided for a nonequilibrium procedure pull-down assay, for an equilibrium direct binding method and its modification into a competition-based measurement and for steady-state measurements based on the effects of ligands on enzyme catalysis.

  19. Synthesis, crystal structure and characterization of new biologically active Cu(II) complexes with ligand derived from N-substituted sulfonamide

    Indian Academy of Sciences (India)

    ADRIANA CORINA HANGAN; ALEXANDRU TURZA; ROXANA LIANA STAN; BOGDAN SEVASTRE; EMÖKE PÁLL; SÎNZIANA CETEAN; LUMINI¸TA SIMONA OPREAN

    2016-05-01

    A new N-sulfonamide ligand (HL1= N-(5-(4-methoxyphenyl)-[1,3,4]–thiadiazole–2-yl)-toluenesulfonamide)and two Cu(II) complexes, $[Cu(L1)­_{2}(py)_{2}]$ (C1) and $[Cu(L2)_{2}(py)_{2}(H_{2}O)]$ (C2) (HL2 = N-(5-(4-methylphenyl)-[1,3,4]–thiadiazole–2-yl)-benzenesulfonamide) were synthesized. The X-ray crystal structuresof the complexes were determined. In the complex C1, the Cu(II) ion is four-coordinated, forming a $CuN_{4}$ chromophore and in the complex C2, the Cu(II) ion is five-coordinated, forming a $CuN_{4}O$ chromophore. Theligand acts as monodentate, coordinating the Cu(II) ion through a single $N_{thiadiazole}$ atom. The molecules fromthe reaction medium (pyridine and water) are also involved in the coordination of the Cu(II) ion. The complexesC1 and C2 are square-planar and a slightly distorted square pyramidal, respectively. The compounds werecharacterized by FT-IR, electronic, EPR spectroscopic and magnetic methods. The nuclease binding activitystudies of the synthesized complexes confirm their capacity to cleave the DNA molecule. The cytotoxicitystudies were carried out on melanoma cell line WM35 which confirm that both compounds inhibit the growthof these cells. They have a higher activity compared to a platinum drug, carboplatin.

  20. Synthesis, Crystal Structure and Luminescent Properties of a Novel Zinc(Ⅱ) Complex of N-Acetyl-L-glutamic Acid and Imidazole Ligands

    Institute of Scientific and Technical Information of China (English)

    CHENG Meng-Qi; MA Lu-Fang; WANG Li-Ya; WANG Jian-Ge

    2006-01-01

    A novel complex (Zn(Im)2(A-glu)·0.5H2O (Im = imidazole, A-glu = N-acetyl- L-glutamic acid) has been synthesized from the reaction of A-glu with Zn(CH3COO)2(2H2O in the presence of Im at 65 ℃, and structurally characterized by single-crystal X-ray diffraction. The complex crystallizes in tetragonal, space group P43212 with a = b = 8.9078(6), c = 43.458(6) (A), C26H36N10O11Zn2, Mr = 795.39, V = 3448.3(6) (A)3, Dc = 1.532 g/cm3, Z = 4, μ(MoK() = 1.461 mm(1, F(000) = 1640, the final R = 0.0453 and wR = 0.0992. X-ray analysis reveals that the crystal structure is constructed by mixed ligands. A-glu adopts the bis-monodentate coordination mode linking two adjacent metal ions to form a one-dimensional chain. Zinc(Ⅱ) ions are four-coordinated with a distorted tetrahedral geometry. Luminescent properties of the complex have been inves- tigated.

  1. 1D zigzag chain and 0D monomer Cd(II)/Zn(II) compounds based on flexible phenylenediacetic ligand: Synthesis, crystal structures and fluorescent properties

    Science.gov (United States)

    Yang, Fang; Ren, Yixia; Li, Dongsheng; Fu, Feng; Qi, Guangcai; Wang, Yaoyu

    2008-12-01

    Three novel Cd(II)/Zn(II) compounds, [Cd 2(poda) 2(phen) 3(H 2O)] n· nEtOH·3 nH 2O (1), [Zn(poda) 2(bpy)(H 2O)] n(2) and [Zn(Hpoda) 2(bpy)] (3) (H 2poda = 1,2-phenylenediacetic acid, phen = 1,10-phenanthroline, bpy = 2,2'-bipyridyl), have been synthesized and characterized by IR, TG, fluorescent spectrum and single-crystal X-ray diffraction techniques. In 1, poda 2- anions link the adjacent Cd(II) centers to generate a 1D zigzag chain. Furthermore, an unprecedented four-footed "8-shaped" mixed water-ethanol (H 2O) 6(C 2H 5OH) 2 cluster connects four double chains based on 1D zigzag chain into 3D supramolecular architecture. By bis(chelate-monodentate) fashion of poda 2- ligand, compound 2 exhibits 1D zigzag chains, which forming a dense zipper-like 2D structure via strong π-π stacking interactions. Differed from 1 and 2, compound 3 has a mononuclear motif, and displays a 3D 6-connected α-Po net hydrogen-bonded topology. The structure-related solid-state fluorescence spectra of compounds 1 and 2 have been determined.

  2. Synthesis, characterization and magnetic property of a succinate bridged 1D coordination polymer of cobalt(II) containing benzidine as end-capping ligand

    Science.gov (United States)

    Roy, Subhasis; Choubey, Somnath; Khan, Sumitava; Bhar, Kishalay; Ribas, Joan; Ghosh, Barindra Kumar

    2014-03-01

    A new bis(monodentate) succinate bridged 1D coordination polymer [Co(bnzd)2(μ-suc)(OH2)2]nṡ(H2O)n (1) (bnzd = benzidine; suc = succinate dianion) has been isolated using a one-pot reaction of the building components, and characterized structurally and magneto-structurally. Single crystal X-ray diffraction measurement reveals that each cobalt(II) center adopts an octahedral geometry with a CoN2O4 chromophore coordinated by two N atoms of two bnzd ligands, two O atoms of two water molecules and two O atoms of two suc units. In crystalline state, individual units of 1 self-assemble through cooperative N-H⋯O, O-H⋯O and C-H⋯O hydrogen bonds and C-H⋯π interactions affording a 3D network structure. Variable-temperature magnetic susceptibility measurement of 1 in the 2-300 K temperature range shows weak antiferromagnetic coupling among the adjacent cobalt(II) centers presumably due to long bridging arm of the dicarboxylate.

  3. Transition metal coordination polymers with polycarboxylic acid as bridging ligands: Synthesis and structure characterization of [Fe(μ4-bta)0.5(phen)(OH)]n

    Institute of Scientific and Technical Information of China (English)

    XU; Jiqing; CHU; Deqing; YU; Jiehui; WANG; Tiegang; TANG; A

    2004-01-01

    A new 2D (two-dimensional) coordination polymer, [Fe(μ4-bta)0.5(phen)(OH)]n (1), has been hydrothermally synthesized with FeCl3·6H2O, Na4bta (H4bta = 1,2,4,5-benzentetra- carboxylic acid), 1,10-phen (1,10-phenanthroline) and H2O as raw materials. The crystals of the compound belong to monoclinic P21/n space group, a = 1.0129(2) nm, b = 0.9265(2) nm, c = 1.5696(3) nm,β = 91.37(3) o, V = 1.4721(5) nm3, Z = 3, final R1 = 0.0292, Wr2 = 0.0798 for 2572 [I > 2σ (I )] observed reflections. The result of structure determination shows that in the compound each bta ligand is connected with four FeIII, forming a new μ4-coordination mode. Four deprotonated carboxylic groups of bta link to FeIII ions alternatively through monodentate and bidentate coordination fashion, constructing 2D layer network. The measurement of variable temperature magnetic susceptibility indicates that there exist antiferromagnetic interactions between FeIII ions in the compound. The TGA spectrum displays relatively fine thermal stability of the compound. In addition, IR and UV-Vis spectra of compound 1 have also been measured.

  4. Transition metal coordination polymers with polycarboxylic acid as bridging ligands:Synthesis and structure characterization of [Fe(μ4-bta)0.5(phen)(OH)]n

    Institute of Scientific and Technical Information of China (English)

    XU Jiqing; CHU Deqing; YU Jiehui; WANG Tiegang; TANG Aoqing

    2004-01-01

    A new 2D (two-dimensional) coordination polymer, [Fe(μ4-bta)0.5(phen)(OH)]n (1), has been hydrothermally synthesized with FeCl3·6H2O, Na4bta (H4bta = 1,2,4,5-benzentetra- carboxylic acid), 1,10-phen (1,10-phenanthroline) and H2O as raw materials. The crystals of the compound belong to monoclinic P21/n space group, a = 1.0129(2) nm, b = 0.9265(2) nm, c = 1.5696(3) nm,β = 91.37(3) o, V = 1.4721(5) nm3, Z = 3, final R1 = 0.0292, Wr2 = 0.0798 for 2572 [I > 2σ (I )] observed reflections. The result of structure determination shows that in the compound each bta ligand is connected with four FeIII, forming a new μ4-coordination mode. Four deprotonated carboxylic groups of bta link to FeIII ions alternatively through monodentate and bidentate coordination fashion, constructing 2D layer network. The measurement of variable temperature magnetic susceptibility indicates that there exist antiferromagnetic interactions between FeIII ions in the compound. The TGA spectrum displays relatively fine thermal stability of the compound. In addition, IR and UV-Vis spectra of compound 1 have also been measured.

  5. Synthesis and characterization of fac-[M(CO)3(P)(OO)] and cis-trans-[M(CO)2(P)2(OO)] complexes (M = Re, (99m)Tc) with acetylacetone and curcumin as OO donor bidentate ligands.

    Science.gov (United States)

    Triantis, Charalampos; Tsotakos, Theodoros; Tsoukalas, Charalampos; Sagnou, Marina; Raptopoulou, Catherine; Terzis, Aris; Psycharis, Vassilis; Pelecanou, Maria; Pirmettis, Ioannis; Papadopoulos, Minas

    2013-11-18

    The synthesis and characterization of neutral mixed ligand complexes fac-[M(CO)3(P)(OO)] and cis-trans-[M(CO)2(P)2(OO)] (M = Re, (99m)Tc), with deprotonated acetylacetone or curcumin as the OO donor bidentate ligands and a phosphine (triphenylphosphine or methyldiphenylphosphine) as the monodentate P ligand, is described. The complexes were synthesized through the corresponding fac-[M(CO)3(H2O)(OO)] (M = Re, (99m)Tc) intermediate aqua complex. In the presence of phosphine, replacement of the H2O molecule of the intermediate complex at room temperature generates the neutral tricarbonyl monophosphine fac-[Re(CO)3(P)(OO)] complex, while under reflux conditions further replacement of the trans to the phosphine carbonyl generates the new stable dicarbonyl bisphosphine complex cis-trans-[Re(CO)2(P)2(OO)]. The Re complexes were fully characterized by elemental analysis, spectroscopic methods, and X-ray crystallography showing a distorted octahedral geometry around Re. Both the monophosphine and the bisphosphine complexes of curcumin show selective binding to β-amyloid plaques of Alzheimer's disease. At the (99m)Tc tracer level, the same type of complexes, fac-[(99m)Tc(CO)3(P)(OO)] and cis-trans-[(99m)Tc(CO)2(P)2(OO)], are formed introducing new donor combinations for (99m)Tc(I). Overall, β-diketonate and phosphine constitute a versatile ligand combination for Re(I) and (99m)Tc(I), and the successful employment of the multipotent curcumin as β-diketone provides a solid example of the pharmacological potential of this system.

  6. 平面正方形配合物取代反应的机理和反位效应%Ligand substitution reaction mechanism and trans-effect of square-planar complexes

    Institute of Scientific and Technical Information of China (English)

    于兆文; 张武; 滕洪梅

    2013-01-01

      平面正方形配合物反位效应的起因已经困惑了人们将近一个世纪。作者根据平面正方形配合物取代反应的缔合机理,考虑了配体取代反应进行过程中配体间的排斥作用,分析了最易形成的中间体和过渡态2的空间构型;揭示了反位效应的起因,提出了一种配体排斥理论,从而比较系统和圆满地解释了平面正方形配合物取代反应的反位效应。%The cause of trans-effect for square planar complexes has puzzled people for nearly a century .Based on the fact that the ligand substitution reactions of square-planar complexes re-act by a SN2 mechanism ,the most preferable configurations for the intermediate and transition state 2 were deduced while the repulsions between the ligands in the reaction pathway were considered .Furthermore ,the causes of trans-effect were revealed ,and a new theory---ligand repulsion theory was proposed to illustrate the trans-effect . It was found that as-proposed theory can be well adopted to independently and systematically explain the trans-effect for all kinds of monodentate ligands .

  7. Cofactor-Controlled Chirality of Tropoisomeric Ligand

    NARCIS (Netherlands)

    Théveau, L.; Bellini, R.; Dydio, P.; Szabo, Z.; van der Werf, A.; Sander, R.A.; Reek, J.N.H.; Moberg, C.

    2016-01-01

    A new tropos ligand with an integrated anion receptor receptor site has been prepared. Chiral carboxylate and phosphate anions that bind in the anion receptor unit proved capable of stabilizing chiral conformations of the achiral flexible bidentate biaryl phosphite ligand, as shown by variable

  8. Flexible Ligand Docking Using Evolutionary Algorithms

    DEFF Research Database (Denmark)

    Thomsen, Rene

    2003-01-01

    The docking of ligands to proteins can be formulated as a computational problem where the task is to find the most favorable energetic conformation among the large space of possible protein–ligand complexes. Stochastic search methods such as evolutionary algorithms (EAs) can be used to sample large...

  9. Flexible Ligand Docking Using Differential Evolution

    DEFF Research Database (Denmark)

    Thomsen, René

    2003-01-01

    the most favorable energetic conformation among the large space of possible protein-ligand complexes. Stochastic search methods, such as evolutionary algorithms (EAs), can be used to sample large search spaces effectively and is one of the preferred methods for flexible ligand docking. The differential...

  10. Rhodium olefin complexes of diiminate type ligands

    NARCIS (Netherlands)

    Willems, Sander Theodorus Hermanus

    2003-01-01

    The mono-anionic beta-diiminate ligand (ArNC(CH3)CHC(CH3)NAr) on several previous occasions proved useful in stabilising low coordination numbers for both early and late transition metals. In this thesis the reactivity of the rhodium olefin complexes of one of these beta-diiminate ligands (Ar = 2,6-

  11. 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 exam...

  12. Asymmetric catalysis based on tropos ligands.

    Science.gov (United States)

    Aikawa, Kohsuke; Mikami, Koichi

    2012-11-21

    All enantiopure atropisomeric (atropos) ligands essentially require enantiomeric resolution or synthetic transformation from a chiral pool. In sharp contrast, the use of tropos (chirally flexible) ligands, which are highly modular, versatile, and easy to synthesize without enantiomeric resolution, has recently been the topic of much interest in asymmetric catalysis. Racemic catalysts bearing tropos ligands can be applied to asymmetric catalysis through enantiomeric discrimination by the addition of a chiral source, which preferentially transforms one catalyst enantiomer into a highly activated catalyst enantiomer. Additionally, racemic catalysts bearing tropos ligands can also be utilized as atropos enantiopure catalysts obtained via the control of chirality by a chiral source followed by the memory of chirality. In this feature article, our results on the asymmetric catalysis via the combination of various central metals and tropos ligands are summarized.

  13. Ligand binding mechanics of maltose binding protein.

    Science.gov (United States)

    Bertz, Morten; Rief, Matthias

    2009-11-13

    In the past decade, single-molecule force spectroscopy has provided new insights into the key interactions stabilizing folded proteins. A few recent studies probing the effects of ligand binding on mechanical protein stability have come to quite different conclusions. While some proteins seem to be stabilized considerably by a bound ligand, others appear to be unaffected. Since force acts as a vector in space, it is conceivable that mechanical stabilization by ligand binding is dependent on the direction of force application. In this study, we vary the direction of the force to investigate the effect of ligand binding on the stability of maltose binding protein (MBP). MBP consists of two lobes connected by a hinge region that move from an open to a closed conformation when the ligand maltose binds. Previous mechanical experiments, where load was applied to the N and C termini, have demonstrated that MBP is built up of four building blocks (unfoldons) that sequentially detach from the folded structure. In this study, we design the pulling direction so that force application moves the two MBP lobes apart along the hinge axis. Mechanical unfolding in this geometry proceeds via an intermediate state whose boundaries coincide with previously reported MBP unfoldons. We find that in contrast to N-C-terminal pulling experiments, the mechanical stability of MBP is increased by ligand binding when load is applied to the two lobes and force breaks the protein-ligand interactions directly. Contour length measurements indicate that MBP is forced into an open conformation before unfolding even if ligand is bound. Using mutagenesis experiments, we demonstrate that the mechanical stabilization effect is due to only a few key interactions of the protein with its ligand. This work illustrates how varying the direction of the applied force allows revealing important details about the ligand binding mechanics of a large protein.

  14. The ligand binding domain controls glucocorticoid receptor dynamics independent of ligand release.

    Science.gov (United States)

    Meijsing, Sebastiaan H; Elbi, Cem; Luecke, Hans F; Hager, Gordon L; Yamamoto, Keith R

    2007-04-01

    Ligand binding to the glucocorticoid receptor (GR) results in receptor binding to glucocorticoid response elements (GREs) and the formation of transcriptional regulatory complexes. Equally important, these complexes are continuously disassembled, with active processes driving GR off GREs. We found that co-chaperone p23-dependent disruption of GR-driven transcription depended on the ligand binding domain (LBD). Next, we examined the importance of the LBD and of ligand dissociation in GR-GRE dissociation in living cells. We showed in fluorescence recovery after photobleaching studies that dissociation of GR from GREs is faster in the absence of the LBD. Furthermore, GR interaction with a target promoter revealed ligand-specific exchange rates. However, using covalently binding ligands, we demonstrated that ligand dissociation is not required for receptor dissociation from GREs. Overall, these studies showed that activities impinging on the LBD regulate GR exchange with GREs but that the dissociation of GR from GREs is independent from ligand dissociation.

  15. 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

  16. Multicomponent mixtures for cryoprotection and ligand solubilization

    Directory of Open Access Journals (Sweden)

    Lidia Ciccone

    2015-09-01

    Full Text Available Mixed cryoprotectants have been developed for the solubilization of ligands for crystallization of protein–ligand complexes and for crystal soaking. Low affinity lead compounds with poor solubility are problematic for structural studies. Complete ligand solubilization is required for co-crystallization and crystal soaking experiments to obtain interpretable electron density maps for the ligand. Mixed cryo-preserving compounds are needed prior to X-ray data collection to reduce radiation damage at synchrotron sources. Here we present dual-use mixes that act as cryoprotectants and also promote the aqueous solubility of hydrophobic ligands. Unlike glycerol that increases protein solubility and can cause crystal melting the mixed solutions of cryo-preserving compounds that include precipitants and solubilizers, allow for worry-free crystal preservation while simultaneously solubilizing relatively hydrophobic ligands, typical of ligands obtained in high-throughput screening. The effectiveness of these mixture has been confirmed on a human transthyretin crystals both during crystallization and in flash freezing of crystals.

  17. Coordinate unsaturation with fluorinated ligands

    Energy Technology Data Exchange (ETDEWEB)

    Rack, J.L.; Hurlburt, P.K.; Anderson, O.P.; Strauss, S.H. [Colorado State Univ., Ft. Collins, CO (United States)

    1993-12-31

    The preparation and characterization of Zn(OTeF{sub 5}){sub 2} has resulted in a model compound with which to explore the concept of coordinative unsaturation. The coordination of solvents of varying donicity and dielectric constant to the Zn(II) ions in Zn(OTeF{sub 5}){sub 2} was studied by vapor phase monometry, NMR and IR spectroscopy, conductimetry, and X-Ray crystallography. The structures of [Zn(C{sub 6}H{sub 5}NO{sub 2}){sub 2}(OTeF{sub 5})2]2 and Zn(C{sub 6}H{sub 5}NO{sub 2}){sub 3}(OTEF{sub 5}){sub 2} demonstrate the electronic flexibility of some weakly coordinating solvents in that nitrobenzene can function as either an {eta}{sup 1}O or {eta}{sup 2}O,O`-ligand. The dependence of the number of bound solvent molecules and the degree of OTeF{sub 5}{minus} dissociation on solvent donor number and dielectric constant will be presented.

  18. Distribution of unselectively bound ligands along DNA.

    Science.gov (United States)

    Lando, Dmitri Y; Nechipurenko, Yury D

    2008-10-01

    Unselective and reversible adsorption of ligands on DNA for a model of binding proposed by Zasedatelev, Gursky, and Volkenshtein is considered. In this model, the interaction between neighboring ligands located at the distance of i binding centers is characterized by the statistical weight ai. Each ligand covers L binding centers. For this model, expressions for binding averages are represented in a new simple form. This representation is convenient for the calculation of the fraction of inter-ligand distances of i binding centers fd(i) and the fraction of binding centers included in the distances of i binding centers fbc(i) for various types of interaction between bound ligands. It is shown that, for non-cooperative binding, contact cooperativity and long-range cooperativity, the fraction of the zero inter-ligand distance fd(0) is maximal at any relative concentration of bound ligands (r). Calculations demonstrate that, at low r, fd(0) approximately r.ao, and fd(i) approximately r at 11/r-L, then fd(i) rapidly decreases with i at any r for all types of inter-ligand interaction. At high ligand concentration (r is close to rmax=L(-1)), fd(0) is close to unity and fd(i) rapidly decreases with i for any type of inter-ligand interaction. For strong contact cooperativity, fd(0) is close to unity in a much lager r interval ((0.5-1).rmax), and fd(1) approximately ao(-1) at r approximately 0.5.rmax. In the case of long-range interaction between bound ligands, the dependence fd(i) is more complex and has a maximum at i approximately (1/r-L)1/2 for anti-cooperative binding. fbc(i) is maximal at i approximately 1/r-L for all types of binding except the contact cooperativity. A strong asymmetry in the influence of contact cooperativity and anticooperativity on the ligand distribution along DNA is demonstrated.

  19. Tungsten(VI) hexahydride complexes supported by chelating triphosphine ligands: Protonation to give [eta][sup 2]-dihydrogen complexes and catalytic dehydrogenation of cyclooctane to cyclooctene

    Energy Technology Data Exchange (ETDEWEB)

    Michos, D.; Xiaoliang Luo; Faller, J.W.; Crabtree, R.H. (Yale Univ., New Haven, CT (United States))

    1993-04-14

    Reactions of WCl[sub 4](PPh[sub 3])[sub 2][center dot]CH[sub 2]Cl[sub 2] with the chelating triphosphine (triphos) ligands PPh(CH[sub 2]CH[sub 2]PPh[sub 2])[sub 2] (PP[sub 2]), PPh(C[sub 6]H[sub 4]-o-PPh[sub 2])[sub 2] (TP), and MeC(CH[sub 2]PPh[sub 2])[sub 3] (P[sub 3]) in refluxing benzene or toluene give WCl[sub 4](triphos) (triphos = PP[sub 2] (1), TP (2), (3)). Treat of 1-3 with LiAlH[sub 4] in Et[sub 2]O at room temperature followed by hydrolysis in THF at 0[degrees]C affords WH[sub 6](triphos) (triphos = PP[sub 2] (4), TP (5), P[sub 3] (6)), which are the first tungsten polyhydride complexes supported by a chelating triphosphine ligand. Variable-temperature [sup 1]H NMR spectra and T[sub 1] data of 4-6 are consistent with the formulation of them as classical hexahydride complexes containing no [eta][sup 2]-H[sub 2] ligands. Reaction of 4 with Ph[sub 3]SiH in refluxing THF gives the rare silyl polyhydride complex WH[sub 5](SiPh[sub 3])(PP[sub 2]) (7). Protonation of 4-6 with HBF[sub 4][center dot]OEt[sub 2] in CD[sub 2]Cl[sub 2] at 193 K affords the cationic nonclassical [eta][sup 2]-H[sub 2] complexes [WH[sub 7[minus]2x]([eta][sup 2]-H[sub 2])[sub x](triphos)][sup +] (triphos = PP[sub 2] (8), TP (9), P[sub 3] (10); x = 1-3). Deprotonation of 8-10 with NEt[sub 3] regenerates the parent hexahydrides 4-6 quantitatively. The variable-temperature [sup 1]H NMR T[sub 1] data for the hydride resonances of 8-10 are consistent with the nonclassical [eta][sup 2]-H[sub 2] coordination. In the presence of tert-butylethylene as a hydrogen acceptor, complexes 4 and ReH[sub 5](PP[sub 2]) (11) are active catalysts for the thermal dehydrogenation of cyclooctane to cyclooctene, whereas their analogues containing monodentate phosphine ligands are inactive under similar conditions. 42 refs., 1 fig., 1 tab.

  20. Synthesis, Characterization, and Crystal Structure of a Novel Copper(II) Complex with an Asymmetric Coordinated 2,2'-Bipyridine Derivative: A Model for the Associative Complex in the Ligand-Substitution Reactions of [Cu(tren)L](2+)?

    Science.gov (United States)

    Lu Zl, Zhong-lin; Duan Cy, Chun-ying; Tian Yp, Yu-peng; You Xz, Xiao-zeng; Huang Xy, Xiao-ying

    1996-04-10

    The titled compound, (tris(2-aminoethyl)amine)(4,5-diazafluoren-9-one) copper(II) perchlorate, [Cu(C(6)H(18)N(4))(C(11)H(6)N(2)O)(ClO(4))(2)], 1, has been designed, synthesized, and characterized. The electronic and ESR spectra are very different from those of [Cu(tren)L](2+) complexes where L is monodentate ligand. The X-ray analysis revealed that the complex crystallizes in the monoclinic space group P2(1)/c, with a = 10.726(6) Å, b = 14.921(7) Å, c = 14.649(4) Å, beta = 95.13(3) degrees, and Z = 4. The copper(II) ion is coordinated by four nitrogen atoms from tris(2-aminoethyl)amine (tren) and two nitrogen atoms from 4,5-diazafluoren-9-one (dzf) to form an unusual six-coordinate (4 + 1 + 1') geometry. The structure is very rare, and to our knowledge, it is the first example of an asymmetric bidentate phenanthroline derivative metal complex. The structure could be used as a model of the associative complex in the ligand-exchange and ligand-substitution reactions of [Cu(tren)L](2+) and the catalytic mechanisms of enzymes involving copper sites. From the electronic and variable-temperature ESR spectra in solution, the possible mechanism of these reactions has also been proposed. As a comparison, the complex [Cu(tren)(ImH)(ClO(4))(2)], 2, was also synthesized and characterized, where ImH is imidazole.

  1. Automated design of ligands to polypharmacological profiles

    Science.gov (United States)

    Besnard, Jérémy; Ruda, Gian Filippo; Setola, Vincent; Abecassis, Keren; Rodriguiz, Ramona M.; Huang, Xi-Ping; Norval, Suzanne; Sassano, Maria F.; Shin, Antony I.; Webster, Lauren A.; Simeons, Frederick R.C.; Stojanovski, Laste; Prat, Annik; Seidah, Nabil G.; Constam, Daniel B.; Bickerton, G. Richard; Read, Kevin D.; Wetsel, William C.; Gilbert, Ian H.; Roth, Bryan L.; Hopkins, Andrew L.

    2012-01-01

    The clinical efficacy and safety of a drug is determined by its activity profile across multiple proteins in the proteome. However, designing drugs with a specific multi-target profile is both complex and difficult. Therefore methods to rationally design drugs a priori against profiles of multiple proteins would have immense value in drug discovery. We describe a new approach for the automated design of ligands against profiles of multiple drug targets. The method is demonstrated by the evolution of an approved acetylcholinesterase inhibitor drug into brain penetrable ligands with either specific polypharmacology or exquisite selectivity profiles for G-protein coupled receptors. Overall, 800 ligand-target predictions of prospectively designed ligands were tested experimentally, of which 75% were confirmed correct. We also demonstrate target engagement in vivo. The approach can be a useful source of drug leads where multi-target profiles are required to achieve either selectivity over other drug targets or a desired polypharmacology. PMID:23235874

  2. Ligand inducible assembly of a DNA tetrahedron.

    Science.gov (United States)

    Dohno, Chikara; Atsumi, Hiroshi; Nakatani, Kazuhiko

    2011-03-28

    Here we show that a small synthetic ligand can be used as a key building component for DNA nanofabrication. Using naphthyridinecarbamate dimer (NCD) as a molecular glue for DNA hybridization, we demonstrate NCD-triggered formation of a DNA tetrahedron.

  3. Nye ligander for Pt-MOF strukturer

    OpenAIRE

    Jakobsen, Søren

    2006-01-01

    Metalorganic frameworks (MOFs) are a new type of compounds which have been intensely investigated during the last few years. They have been synthesized using a wide variety of metals and ligands constructing a vast number of 1, 2 and 3 dimensional structures, some of which possess zeolite-type physics and chemistry. Our approach is to incorporate platinum metal sites into the structures making them bimetallic and potentially catalytically active. Therefore a number of N-N-type ligands (dii...

  4. SnapShot: GPCR-Ligand Interactions.

    Science.gov (United States)

    Ghosh, Eshan; Nidhi, Kumari; Shukla, Arun K

    2014-12-18

    G-protein-coupled receptors enable cells to recognize numerous external stimuli and to transmit corresponding signals across the plasma membrane to trigger appropriate cellular responses. Crystal structures of a number of these receptors have now been determined in inactive and active conformations bound to chemically and functionally distinct ligands. These crystal structures illustrate overall receptor organization and atomic details of ligand-receptor interactions. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. A versatile dinucleating ligand containing sulfonamide groups

    DEFF Research Database (Denmark)

    Sundberg, Jonas; Witt, Hannes; Cameron, Lisa

    2014-01-01

    Copper, iron, and gallium coordination chemistries of the new pentadentate bis-sulfonamide ligand 2,6-bis(N-2-pyridylmethylsulfonamido)-4-methylphenol (psmpH3) were investigated. PsmpH3 is capable of varying degrees of deprotonation, and notably, complexes containing the fully trideprotonated...... 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...... flexibility since additional one- and three-atom bridging ligands bridge the two copper(II) ions in each complex, respectively. This gives rise to a difference of 0.4 Å in the Cu···Cu distances. Complexes with 2:3 and 2:1 ligand/metal stoichiometries for the divalent and trivalent metal ions, respectively...

  6. 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.

  7. 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.

  8. Fully Flexible Docking of Medium Sized Ligand Libraries with RosettaLigand.

    Directory of Open Access Journals (Sweden)

    Samuel DeLuca

    Full Text Available RosettaLigand has been successfully used to predict binding poses in protein-small molecule complexes. However, the RosettaLigand docking protocol is comparatively slow in identifying an initial starting pose for the small molecule (ligand making it unfeasible for use in virtual High Throughput Screening (vHTS. To overcome this limitation, we developed a new sampling approach for placing the ligand in the protein binding site during the initial 'low-resolution' docking step. It combines the translational and rotational adjustments to the ligand pose in a single transformation step. The new algorithm is both more accurate and more time-efficient. The docking success rate is improved by 10-15% in a benchmark set of 43 protein/ligand complexes, reducing the number of models that typically need to be generated from 1000 to 150. The average time to generate a model is reduced from 50 seconds to 10 seconds. As a result we observe an effective 30-fold speed increase, making RosettaLigand appropriate for docking medium sized ligand libraries. We demonstrate that this improved initial placement of the ligand is critical for successful prediction of an accurate binding position in the 'high-resolution' full atom refinement step.

  9. 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.

  10. New polypyridine anchoring ligands for coordination complexes and surface functionalization

    OpenAIRE

    Müller, Steffen

    2015-01-01

    This PhD thesis focuses on the synthesis of new polypyridine anchoring ligands and several dfferent applications. The ligands consist of a coordinating part, a flexible linker and an anchoring group. Due to the fact that different anchoring groups were used, the ligands can be applied for several types of surface-materials. Using these anchoring ligands, several coordination complexes were synthesized. Ruthenium-based complexes, bearing an ion-sensitive ligand, were tested towards...

  11. Latitudinal variability of arsine, germane and phosphine in Jupiter's troposphere

    Science.gov (United States)

    Giles, Rohini Sara; Fletcher, Leigh N.; Irwin, Patrick Gerard Joseph

    2016-10-01

    High-resolution 5-μm observations of Jupiter from the CRIRES instrument at the Very Large Telescope are used to measure latitudinal variability in AsH3, GeH4 and PH3. The 5-micron region is a spectral window allowing us to probe down to Jupiter's middle troposphere (4-8 bar). CRIRES observations in 2012 and 2013 provide high-resolution (R=96,000) latitudinally-resolved spectra in the 4.7-5.2 μm region. In the middle troposphere, AsH3, GeH4and PH3 are disequilibrium species that are only present because of rapid upwelling from deeper regions of the planet. Their observed abundances depend on the chemical lifetimes, the strength of the vertical mixing and the rate of photolytic destruction, and are therefore likely to vary with latitude. We analyse the CRIRES observations using the NEMESIS radiative transfer code and retrieval algorithm in order to search for any latitudinal variability in the disequilibrium species. We find that there is a significant degeneracy between the retrieved gaseous abundances and the cloud structure - specifically, the scattering properties of the main tropospheric cloud deck, and the presence/absence of an additional deep cloud. Because of these degeneracies, there is no clear evidence for any variability in GeH4. However, for AsH3 and PH3, there are significant latitudinal differences in the observed lineshape that cannot be accounted for by clouds. We conclude that both of these gases show an enhancement at high latitudes. In the case of AsH3, the retrieved abundance varies from subsolar in the equatorial regions (as seen in previous studies) to supersolar in the polar regions. Our findings are in contrast with the theoretical simulations of Wang et al. (2016, doi:10.1016/j.icarus.2016.04.027), which predict that AsH3 and PH3 should not vary with latitude, and that GeH4 should decrease in abundance at high latitudes.

  12. Multiple ligand simultaneous docking: orchestrated dancing of ligands in binding sites of protein.

    Science.gov (United States)

    Li, Huameng; Li, Chenglong

    2010-07-30

    Present docking methodologies simulate only one single ligand at a time during docking process. In reality, the molecular recognition process always involves multiple molecular species. Typical protein-ligand interactions are, for example, substrate and cofactor in catalytic cycle; metal ion coordination together with ligand(s); and ligand binding with water molecules. To simulate the real molecular binding processes, we propose a novel multiple ligand simultaneous docking (MLSD) strategy, which can deal with all the above processes, vastly improving docking sampling and binding free energy scoring. The work also compares two search strategies: Lamarckian genetic algorithm and particle swarm optimization, which have respective advantages depending on the specific systems. The methodology proves robust through systematic testing against several diverse model systems: E. coli purine nucleoside phosphorylase (PNP) complex with two substrates, SHP2NSH2 complex with two peptides and Bcl-xL complex with ABT-737 fragments. In all cases, the final correct docking poses and relative binding free energies were obtained. In PNP case, the simulations also capture the binding intermediates and reveal the binding dynamics during the recognition processes, which are consistent with the proposed enzymatic mechanism. In the other two cases, conventional single-ligand docking fails due to energetic and dynamic coupling among ligands, whereas MLSD results in the correct binding modes. These three cases also represent potential applications in the areas of exploring enzymatic mechanism, interpreting noisy X-ray crystallographic maps, and aiding fragment-based drug design, respectively.

  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. Organotellurium ligands - designing and complexation reactions

    Indian Academy of Sciences (India)

    Ajai K Singh

    2002-08-01

    A variety of tellurium ligands has been designed and studied for their complexation reactions in the last decade. Of these hybrid telluroethers, halotellurium ligands and polytellurides are the most notable ones. RTe- and polytelluride ions have also been used to design clusters. Ligation of ditelluroethers and several hybrid telluroethers is extensively studied in our laboratories. The ditelluroether ligand RTeCH2TeR (where R = 4-MeOC6H4) (1), similar to dppm [1,2-bis(diphenylphosphino) methane], has been synthesized in good yield (∼80 %) by reacting CHCl3 with RTe- (generated in situ by borohydride reduction of R2Te2). Iodine reacts with 1 to give tetra-iodo derivative, which has intermolecular Te$\\cdots$I interactions resulting in a macro structure containing rectangular Te-I$\\cdots$Te bridges. 1 readily forms four membered rings with Pd(II) and Ru(II). On the formation of this chelate ring, the signal in 125Te NMR spectra shifts significantly upfield (50-60 ppm). The bridging mode of 1 has been shown in [Ru(-cymene)Cl2](-1)[Ru(-cymene)Cl2]. The hybrid telluroether ligands explored are of the types (Te, S), (Te, N) and (Te, O). The tellurium donor site has strong trans influence, which is manifested more strongly in square planar complexes of palladium(II). The morpholine N-donor site has been found to have weaker donor characteristics in (Te, N) ligands than pyridine and alkylamine donor sites of analogous ligands. The singlet oxygen readily oxidises the coordinated Te. This oxidation follows first order kinetics. The complexation reaction of RuCl3.H2O with N-[2-(4-methoxyphenyltelluro)ethyl]phthalimide (2) results in a novel (Te, N, O)-heterocycle, Te-chloro,Te-anisyl-1a-aza-4-oxa-3-tellura-1H, 2H, 4aH-9 fluorenone. The (Te, O) ligands can be used as hemilabile ligands, the oxygen atom temporarily protects the vacant coordination site before the arrival of the substrate. The chelate shifts observed in 125Te NMR spectra of metal complexes of Te-ligands have

  15. 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.

  16. 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.

  17. Sliding tethered ligands add topological interactions to the toolbox of ligand-receptor design

    Science.gov (United States)

    Bauer, Martin; Kékicheff, Patrick; Iss, Jean; Fajolles, Christophe; Charitat, Thierry; Daillant, Jean; Marques, Carlos M.

    2015-09-01

    Adhesion in the biological realm is mediated by specific lock-and-key interactions between ligand-receptor pairs. These complementary moieties are ubiquitously anchored to substrates by tethers that control the interaction range and the mobility of the ligands and receptors, thus tuning the kinetics and strength of the binding events. Here we add sliding anchoring to the toolbox of ligand-receptor design by developing a family of tethered ligands for which the spacer can slide at the anchoring point. Our results show that this additional sliding degree of freedom changes the nature of the adhesive contact by extending the spatial range over which binding may sustain a significant force. By introducing sliding tethered ligands with self-regulating length, this work paves the way for the development of versatile and reusable bio-adhesive substrates with potential applications for drug delivery and tissue engineering.

  18. 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.

  19. Synthesis and Structures of Two Lanthanide Complexes Containing a Mixed Ligand System: [Ln(Phen){sub 2}(L){sub 3}(HL)]·H{sub 2}O [Ln = La, Ce; Phen = Phenanthroline; HL = Salicylic Acid

    Energy Technology Data Exchange (ETDEWEB)

    Iravani, Effat [UNiv. of Applied Science and Technology, Tehran (Iran, Islamic Republic of); Nami, Navabeh; Nabizadeh, Fatemeh; Bayani, Elham [Islamic Azad Univ., Mazandaran (Iran, Islamic Republic of); Neumueller, Bernhard [Philipps-Universitat Marburg, Marburg (Germany)

    2013-11-15

    The reaction of LnCl{sub 3}·7H{sub 2}O [Ln = La (1), Ce (2)] with salicylic acid (HL) and 1,10-phenanthroline (Phen) at 20 .deg. C in H{sub 2}O/ethanol gave after work-up and recrystallization two novel lanthanide complexes with general formula [Ln(Phen){sub 2}(L){sub 3}(HL)]·H{sub 2}O. Compounds 1 and 2 were characterized by IR and UV-Vis spectroscopy, TGA, CHN as well as by X-ray analysis. According to these results, compounds 1 and 2 are isostructural and contain Ln{sup 3+} ions with coordination number nine. Complexes 1 and 2 consist of two Phen, one neutral HL and three L anions (two L anions act as monodentate ligands and the third one is chelating to Ln{sup 3+}). Thermal decomposition led to primary loss of the Phen molecules. Then HL molecules and finally L moieties left the material to give Ln{sub 2}O{sub 3}.

  20. Cationic ruthenium alkylidene catalysts bearing phosphine ligands.

    Science.gov (United States)

    Endo, Koji; Grubbs, Robert H

    2016-02-28

    The discovery of highly active catalysts and the success of ionic liquid immobilized systems have accelerated attention to a new class of cationic metathesis catalysts. We herein report the facile syntheses of cationic ruthenium catalysts bearing bulky phosphine ligands. Simple ligand exchange using silver(i) salts of non-coordinating or weakly coordinating anions provided either PPh3 or chelating Ph2P(CH2)nPPh2 (n = 2 or 3) ligated cationic catalysts. The structures of these newly reported catalysts feature unique geometries caused by ligation of the bulky phosphine ligands. Their activities and selectivities in standard metathesis reactions were also investigated. These cationic ruthenium alkylidene catalysts reported here showed moderate activity and very similar stereoselectivity when compared to the second generation ruthenium dichloride catalyst in ring-closing metathesis, cross metathesis, and ring-opening metathesis polymerization assays.

  1. Flexible Ligand Docking Using Evolutionary Algorithms

    DEFF Research Database (Denmark)

    Thomsen, Rene

    2003-01-01

    The docking of ligands to proteins can be formulated as a computational problem where the task is to find the most favorable energetic conformation among the large space of possible protein–ligand complexes. Stochastic search methods such as evolutionary algorithms (EAs) can be used to sample large...... search spaces effectively and is one of the commonly used methods for flexible ligand docking. During the last decade, several EAs using different variation operators have been introduced, such as the ones provided with the AutoDock program. In this paper we evaluate the performance of different EA...... settings such as choice of variation operators, population size, and usage of local search. The comparison is performed on a suite of six docking problems previously used to evaluate the performance of search algorithms provided with the AutoDock program package. The results from our investigation confirm...

  2. Ligand Intermediates in Metal-Catalyzed Reactions

    Energy Technology Data Exchange (ETDEWEB)

    Gladysz, John A.

    1999-07-31

    The longest-running goal of this project has been the synthesis, isolation, and physical chemical characterization of homogeneous transition metal complexes containing ligand types believed to be intermediates in the metal-catalyzed conversion of CO/H{sub 2}, CO{sub 2}, CH{sub 4}, and similar raw materials to organic fuels, feedstocks, etc. In the current project period, complexes that contain unusual new types of C{sub x}(carbide) and C{sub x}O{sub y} (carbon oxide) ligands have been emphasized. A new program in homogeneous fluorous phase catalysis has been launched as described in the final report.

  3. Efficient chemoenzymatic synthesis of chiral pincer ligands.

    Science.gov (United States)

    Felluga, Fulvia; Baratta, Walter; Fanfoni, Lidia; Pitacco, Giuliana; Rigo, Pierluigi; Benedetti, Fabio

    2009-05-01

    Chiral, nonracemic pincer ligands based on the 6-phenyl-2-aminomethylpyridine and 2-aminomethylbenzo[h]quinoline scaffolds were obtained by a chemoenzymatic approach starting from 2-pyridyl and 2-benzoquinolyl ethanone. In the enantiodifferentiating step, secondary alcohols of opposite absolute configuration were obtained by a baker's yeast reduction of the ketones and by lipase-mediated dynamic kinetic resolution of the racemic alcohols. Their transformation into homochiral 1-methyl-1-heteroarylethanamines occurred without loss of optical purity, giving access to pincer ligands used in enantioselective catalysis.

  4. Silver(I nitrate complexes of three tetrakis-thioether-substituted pyrazine ligands: metal–organic chain, network and framework structures

    Directory of Open Access Journals (Sweden)

    Tokouré Assoumatine

    2017-03-01

    Full Text Available The reaction of the ligand 2,3,5,6-tetrakis[(methylsulfanylmethyl]pyrazine (L1 with silver(I nitrate led to {[Ag(C12H20N2S4](NO3}n, (I, catena-poly[[silver(I-μ-2,3,5,6-tetrakis[(methylsulfanylmethyl]pyrazine] nitrate], a compound with a metal–organic chain structure. The asymmetric unit is composed of two half ligands, located about inversion centres, with one ligand coordinating to the silver atoms in a bis-tridentate manner and the other in a bis-bidentate manner. The charge on the metal atom is compensated for by a free nitrate anion. Hence, the silver atom has a fivefold S3N2 coordination sphere. The reaction of the ligand 2,3,5,6-tetrakis[(phenylsulfanylmethyl]pyrazine (L2 with silver(I nitrate, led to [Ag2(NO32(C32H28N2S4]n, (II, poly[di-μ-nitrato-bis{μ-2,3,5,6-tetrakis[(phenylsulfanylmethyl]pyrazine}disilver], a compound with a metal–organic network structure. The asymmetric unit is composed of half a ligand, located about an inversion centre, that coordinates to the silver atoms in a bis-tridentate manner. The nitrate anion coordinates to the silver atom in a bidentate/monodentate manner, bridging the silver atoms, which therefore have a sixfold S2NO3 coordination sphere. The reaction of the ligand 2,3,5,6-tetrakis[(pyridin-2-ylsulfanylmethyl]pyrazine (L3 with silver(I nitrate led to [Ag3(NO33(C28H24N6S4]n, (III, poly[trinitrato{μ6-2,3,5,6-tetrakis[(pyridin-2-ylsulfanylmethyl]pyrazine}trisilver(I], a compound with a metal–organic framework structure. The asymmetric unit is composed of half a ligand, located about an inversion centre, that coordinates to the silver atoms in a bis-tridentate manner. One pyridine N atom bridges the monomeric units, so forming a chain structure. Two nitrate O atoms also coordinate to this silver atom, hence it has a sixfold S2N2O2 coordination sphere. The chains are linked via a second silver atom, located on a twofold rotation axis, coordinated by the second pyridine N atom. A second nitrate anion

  5. Solid angles III. The role of conformers in solid angle calculations

    CSIR Research Space (South Africa)

    White, D

    1995-06-14

    Full Text Available The values of the solid angles Omega for a range of commonly encountered ligands in organometallic chemistry (phosphines, phosphites, amines, arsines and cyclopentadienyl rings) have been determined. The solid angles were derived from a single...

  6. CLiBE: a database of computed ligand binding energy for ligand-receptor complexes.

    Science.gov (United States)

    Chen, X; Ji, Z L; Zhi, D G; Chen, Y Z

    2002-11-01

    Consideration of binding competitiveness of a drug candidate against natural ligands and other drugs that bind to the same receptor site may facilitate the rational development of a candidate into a potent drug. A strategy that can be applied to computer-aided drug design is to evaluate ligand-receptor interaction energy or other scoring functions of a designed drug with that of the relevant ligands known to bind to the same binding site. As a tool to facilitate such a strategy, a database of ligand-receptor interaction energy is developed from known ligand-receptor 3D structural entries in the Protein Databank (PDB). The Energy is computed based on a molecular mechanics force field that has been used in the prediction of therapeutic and toxicity targets of drugs. This database also contains information about ligand function and other properties and it can be accessed at http://xin.cz3.nus.edu.sg/group/CLiBE.asp. The computed energy components may facilitate the probing of the mode of action and other profiles of binding. A number of computed energies of some PDB ligand-receptor complexes in this database are studied and compared to experimental binding affinity. A certain degree of correlation between the computed energy and experimental binding affinity is found, which suggests that the computed energy may be useful in facilitating a qualitative analysis of drug binding competitiveness.

  7. [Functional selectivity of opioid receptors ligands].

    Science.gov (United States)

    Audet, Nicolas; Archer-Lahlou, Elodie; Richard-Lalonde, Mélissa; Piñeyro-Filpo, Graciela

    2010-01-01

    Opiates are the most effective analgesics available for the treatment of severe pain. However, their clinical use is restricted by unwanted side effects such as tolerance, physical dependence and respiratory depression. The strategy to develop new opiates with reduced side effects has mainly focused on the study and production of ligands that specifically bind to different opiate receptors subtypes. However, this strategy has not allowed the production of novel therapeutic ligands with a better side effects profile. Thus, other research strategies need to be explored. One which is receiving increasing attention is the possibility of exploiting ligand ability to stabilize different receptor conformations with distinct signalling profiles. This newly described property, termed functional selectivity, provides a potential means of directing the stimulus generated by an activated receptor towards a specific cellular response. Here we summarize evidence supporting the existence of ligand-specific active conformations for two opioid receptors subtypes (delta and mu), and analyze how functional selectivity may contribute in the production of longer lasting, better tolerated opiate analgesics. double dagger.

  8. 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.

  9. 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.

  10. Supramolecular architectures constructed using angular bipyridyl ligands

    CERN Document Server

    Barnett, S A

    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 sub 3) sub 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 sub 3) sub 2 and Zn(NO sub 3) sub 2. Whereas Zn(NO sub 3) sub 2 compounds exhibit solvent mediated polymorphism, a range of structures were obtained for the reactions with Cd(NO sub 3) sub 2 , including the first example of a doubly parallel interpenetrated 4.8 sup...

  11. Receptor Binding Ligands to Image Infection

    NARCIS (Netherlands)

    Chianelli, M.; Boerman, O. C.; Malviya, G.; Galli, F.; Oyen, W. J. G.; Signore, A.

    2008-01-01

    The current gold standard for imaging infection is radiolabeled white blood cells. For reasons of safety, simplicity and cost, it would be desirable to have a receptor-specific ligand that could be used for imaging infection and that would allow a differential diagnosis between sterile and septic in

  12. Dissociation of Multisubunit Protein-Ligand Complexes in the Gas Phase. Evidence for Ligand Migration

    Science.gov (United States)

    Zhang, Yixuan; Deng, Lu; Kitova, Elena N.; Klassen, John S.

    2013-10-01

    The results of collision-induced dissociation (CID) experiments performed on gaseous protonated and deprotonated ions of complexes of cholera toxin B subunit homopentamer (CTB5) with the pentasaccharide (β-D-Gal p-(1→3)-β-D-Gal pNAc-(1→4)[α-D-Neu5Ac-(2→3)]-β-D-Gal p-(1→4)-β-D-Glc p (GM1)) and corresponding glycosphingolipid (β-D-Gal p-(1→3)-β-D-Gal pNAc-(1→4)[α-D-Neu5Ac-(2→3)]-β-D-Gal p-(1→4)-β-D-Glc p-Cer (GM1-Cer)) ligands, and the homotetramer streptavidin (S4) with biotin (B) and 1,2-dipalmitoyl- sn-glycero-3-phosphoethanolamine-N-(biotinyl) (Btl), are reported. The protonated (CTB5 + 5GM1)n+ ions dissociated predominantly by the loss of a single subunit, with the concomitant migration of ligand to another subunit. The simultaneous loss of ligand and subunit was observed as a minor pathway. In contrast, the deprotonated (CTB5 + 5GM1)n- ions dissociated preferentially by the loss of deprotonated ligand; the loss of ligand-bound and ligand-free subunit were minor pathways. The presence of ceramide (Cer) promoted ligand migration and the loss of subunit. The main dissociation pathway for the protonated and deprotonated (S4 + 4B)n+/- ions, as well as for deprotonated (S4 + 4Btl)n- ions, was loss of the ligand. However, subunit loss from the (S4 + 4B)n+ ions was observed as a minor pathway. The (S4 + 4Btl)n+ ions dissociated predominantly by the loss of free and ligand-bound subunit. The charge state of the complex and the collision energy were found to have little effect on the relative contribution of the different dissociation channels. Thermally-driven ligand migration between subunits was captured in the results of molecular dynamics simulations performed on protonated (CTB5 + 5GM1)15+ ions (with a range of charge configurations) at 800 K. Notably, the migration pathway was found to be highly dependent on the charge configuration of the ion. The main conclusion of this study is that the dissociation pathways of multisubunit protein-ligand

  13. Targeting Ligand-Dependent and Ligand-Independent Androgen Receptor Signaling in Prostate Cancer

    Science.gov (United States)

    2015-10-01

    Award Number: W81XWH-12-1-0288 TITLE: Targeting Ligand-Dependent and Ligand-Independent Androgen Receptor Signaling in Prostate Cancer...average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed...and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of

  14. Quantum.Ligand.Dock: protein-ligand docking with quantum entanglement refinement on a GPU system.

    Science.gov (United States)

    Kantardjiev, Alexander A

    2012-07-01

    Quantum.Ligand.Dock (protein-ligand docking with graphic processing unit (GPU) quantum entanglement refinement on a GPU system) is an original modern method for in silico prediction of protein-ligand interactions via high-performance docking code. The main flavour of our approach is a combination of fast search with a special account for overlooked physical interactions. On the one hand, we take care of self-consistency and proton equilibria mutual effects of docking partners. On the other hand, Quantum.Ligand.Dock is the the only docking server offering such a subtle supplement to protein docking algorithms as quantum entanglement contributions. The motivation for development and proposition of the method to the community hinges upon two arguments-the fundamental importance of quantum entanglement contribution in molecular interaction and the realistic possibility to implement it by the availability of supercomputing power. The implementation of sophisticated quantum methods is made possible by parallelization at several bottlenecks on a GPU supercomputer. The high-performance implementation will be of use for large-scale virtual screening projects, structural bioinformatics, systems biology and fundamental research in understanding protein-ligand recognition. The design of the interface is focused on feasibility and ease of use. Protein and ligand molecule structures are supposed to be submitted as atomic coordinate files in PDB format. A customization section is offered for addition of user-specified charges, extra ionogenic groups with intrinsic pK(a) values or fixed ions. Final predicted complexes are ranked according to obtained scores and provided in PDB format as well as interactive visualization in a molecular viewer. Quantum.Ligand.Dock server can be accessed at http://87.116.85.141/LigandDock.html.

  15. Fusion of ligand-coated nanoparticles with lipid bilayers: effect of ligand flexibility.

    Science.gov (United States)

    Van Lehn, Reid C; Alexander-Katz, Alfredo

    2014-08-07

    Amphiphilic, monolayer-protected gold nanoparticles (AuNPs) have recently been shown to insert into and fuse with lipid bilayers, driven by the hydrophobic effect. The inserted transmembrane state is stabilized by the "snorkeling" of charged ligand end groups out of the bilayer interior. This snorkeling process is facilitated by the backbone flexibility of the alkanethiol ligands that comprise the monolayer. In this work, we show that fusion is favorable even in the absence of backbone flexibility by modeling the ligands as rigid rods. For rigid ligands, snorkeling is still accommodated by rotations of the ligand with respect to the grafting point, but the process incurs a more significant free energy penalty than if the backbone were fully flexible. We show that the rigid rod model predicts similar trends in the free energy change for insertion as the previous flexible model when the size of the AuNPs is varied. However, the rigidity of the ligand backbone reduces the overall magnitude of the free energy change compared to that of the flexible model. These results thus generalize previous findings to systems with hindered backbone flexibility due to either structural constraints or low temperature.

  16. Imidazol-2-ylidene-N'-phenylureate ligands in alkali and alkaline earth metal coordination spheres--heterocubane core to polymeric structural motif formation.

    Science.gov (United States)

    Naktode, Kishor; Bhattacharjee, Jayeeta; Nayek, Hari Pada; Panda, Tarun K

    2015-04-28

    The synthesis and isolation of two potassium, one lithium and two calcium complexes of imidazol-2-ylidene-N'-phenylureate ligands [Im(R)NCON(H)Ph] [(R = tBu (1a); Mes (1b) and Dipp (1c); Mes = mesityl, Dipp = 2,6-diisopropylphenyl] are described. Potassium complexes, [{κ(2)-(Im(Mes)NCONPh)K}4] (2b) and [{κ(3)-(Im(Dipp)NCONPh)K}2{KN(SiMe3)2}2]n (2c), were prepared in good yields by the reactions of 1b and 1c, respectively, with potassium bis(trimethyl)silyl amide at ambient temperature in toluene. Lithium complex [{(2,6-tBu2-4-Me-C6H2O)Li(Im(tBu)NCON(H)Ph)}2{Im(tBu)NCON(H)Ph}] (3a) was isolated by a one-pot reaction between 1a and LiCH2SiMe3, followed by the addition of 2,6-tBu2-4-Me-C6H2OH in toluene. Calcium complex [{κ(2)-(Im(tBu)NCONPh)Ca{N(SiMe3)2}-{KN(SiMe3)2}]n (4a) was isolated by the one-pot reaction of 1a with [KN(SiMe3)2] and calcium diiodide in THF at ambient temperature. The solid-state structures of ligand 1a and complexes 2b, 2c, 3a and 4a were confirmed by single-crystal X-ray diffraction analysis. It was observed that potassium was coordinated to the oxygen atom of urea group and to the nitrogen atom of the imidazolin-2-imine group, in the solid-state structure of 2b. In complex 4a, the calcium ion was ligated to the monoanionic imidazol-2-ylidene-N'-phenylureate ligand in a bi-dentate (κ(2)) fashion through the oxygen and nitrogen atoms of the isocyanate building block leaving the imidazolin-2-imine fragment uncoordinated. In the solid state of the potassium complex 2c, tri-dentate (κ(3)) coordination from the imidazol-2-ylidene-N'-phenylureate ligand was observed through the oxygen and nitrogen atoms of the isocyanate building block and of the imidazolin-2-imine fragment. In contrast, in the dimeric lithium complex 3a, the neutral imidazol-2-ylidene-N'-phenylureate ligand was bound to the lithium centre in a mono-dentate fashion (κ(1)) through an oxygen atom of the isocyanate moiety. It is to be noted that in each complex thus observed, the

  17. Novel Copper(Ⅱ) and Zinc(Ⅱ) 2-D Supramolecular Structures Based on Carboxylate and 1-Substitutedimidazole Mixed-ligands%Novel Copper(Ⅱ) and Zinc(Ⅱ) 2-D Supramolecular Structures Based on Carboxylate and 1-Substitutedimidazole Mixed-ligands

    Institute of Scientific and Technical Information of China (English)

    CAI Hua; GUO Ying; LI Jian-Gang; WU Yao

    2011-01-01

    Using the ligand bis(3-(1H-imidazol-1-yl)-1-phenylpropan-1-one) L, two novel complexes [CuL2(ph))]·H2O 1 and [ZnL2(tp)] 2 (ph = phthalic acid, tp = terephthalic acid) have been synthesized and their crystal structures were determined by single-crystal X-ray diffraction analysis. Crystal data for 1: triclinic, space group P1^-, a = 9.4300(17), b = 12.148(2), c = 13.721(2) A, a = 109.620(2),β = 94.351(2), y = 94.830(2)°, C32H30N4O7Cu, Mr = 646.14, V= 1466.2(4) A^3, Z = 2, Dc = 1.464 g/cm3, It(MoKa) = 0.801 mm^-1, F(000) = 670, the final R = 0.0337 and wR = 0.0859 for 5122 observed reflections with I 〉 2σ(I), And those for 2: monoclinic, space group P2/n, a = 7.1866(11), b = 14.144(2), c = 14.407(2)/k, β = 101.427(2)°, C32H28N4O6Zn, Mr = 629.95, V = 1435.4(4) A3, Z = 2, Dc = 1.457 g/cm3, μ(MoKa) = 0.908 mm^-1, F(000) = 652, the final R = 0.0438 and wR= 0.0821 for 2546 observed reflections with I〉 2σ(I). In 1 and 2, ph or tp ligauds bridge the six-coordinated copper(Ⅱ) or four-coordinated zinc(Ⅱ) ions forming 1D zigzag chains while L ligands act as the terminal monodentate ligand. It is noted that weak non-classical C-H…O plays the important and dominating roles in the formation of 2D supramolecular architectures of 1, but in 2 non-classical C-H…O and aromatic π…π Stacking interactions are quite important and play dominant roles in the self-assembly of 2D supramolecular architectures.

  18. Amino Acids in Nine Ligand-Prefer Ramachandran Regions

    Directory of Open Access Journals (Sweden)

    Chen Cao

    2015-01-01

    Full Text Available Several secondary structures, such as π-helix and left-handed helix, have been frequently identified at protein ligand-binding sites. A secondary structure is considered to be constrained to a specific region of dihedral angles. However, a comprehensive analysis of the correlation between main chain dihedral angles and ligand-binding sites has not been performed. We undertook an extensive analysis of the relationship between dihedral angles in proteins and their distance to ligand-binding sites, frequency of occurrence, molecular potential energy, amino acid composition, van der Waals contacts, and hydrogen bonds with ligands. The results showed that the values of dihedral angles have a strong preference for ligand-binding sites at certain regions in the Ramachandran plot. We discovered that amino acids preceding the ligand-prefer ϕ/ψ box residues are exposed more to solvents, whereas amino acids following ligand-prefer ϕ/ψ box residues form more hydrogen bonds and van der Waals contacts with ligands. Our method exhibited a similar performance compared with the program Ligsite-csc for both ligand-bound structures and ligand-free structures when just one ligand-binding site was predicted. These results should be useful for the prediction of protein ligand-binding sites and for analysing the relationship between structure and function.

  19. Open-shell organometallics: reactivity at the ligand

    NARCIS (Netherlands)

    W.I. Dzik; B. de Bruin

    2011-01-01

    The purpose of this review is to show that (cooperative) ligand radical reactivity can be effectively employed in synthetic organometallic chemistry and catalysis to achieve selectivity in radical-type transformations. The ‘redox non-innocence’ of ligands, and the controlled reactivity of ‘ligand ra

  20. Triple Bioaffinity Mass Spectrometry Concept for Thyroid Transporter Ligands

    NARCIS (Netherlands)

    Aqai, P.; Fryganas, C.; Mizuguchi, M.; Haasnoot, W.; Nielen, M.W.F.

    2012-01-01

    For the analysis of thyroid transporter ligands, a triple bioaffinity mass spectrometry (BioMS) concept was developed, with the aim at three different analytical objectives: rapid screening of any ligand, confirmation of known ligands in accordance with legislative requirements, and identification o

  1. Glycomimetic ligands for the human asialoglycoprotein receptor.

    Science.gov (United States)

    Mamidyala, Sreeman K; Dutta, Sanjay; Chrunyk, Boris A; Préville, Cathy; Wang, Hong; Withka, Jane M; McColl, Alexander; Subashi, Timothy A; Hawrylik, Steven J; Griffor, Matthew C; Kim, Sung; Pfefferkorn, Jeffrey A; Price, David A; Menhaji-Klotz, Elnaz; Mascitti, Vincent; Finn, M G

    2012-02-01

    The asialoglycoprotein receptor (ASGPR) is a high-capacity galactose-binding receptor expressed on hepatocytes that binds its native substrates with low affinity. More potent ligands are of interest for hepatic delivery of therapeutic agents. We report several classes of galactosyl analogues with varied substitution at the anomeric, C2-, C5-, and C6-positions. Significant increases in binding affinity were noted for several trifluoromethylacetamide derivatives without covalent attachment to the protein. A variety of new ligands were obtained with affinity for ASGPR as good as or better than that of the parent N-acetylgalactosamine, showing that modification on either side of the key C3,C4-diol moiety is well tolerated, consistent with previous models of a shallow binding pocket. The galactosyl pyranose motif therefore offers many opportunities for the attachment of other functional units or payloads while retaining low-micromolar or better affinity for the ASGPR.

  2. Leaching behavior of butanedionedioxime as gold ligand

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Butanedionedioxime, a small organic compound with low-toxicity and good chemical stability, has been proposed as an effective gold ligand in gold extraction. The result of experiment shows that: 1) highly effective gold lixiviantcan be composed of butanedionedioxime (BDM) with many oxidants, especially potassium permanganate; 2)in the leaching system of BD M- K M nO4 the suitable Ox/Lig(ratio of oxidants to gold ligands) tange is 0.20 ~ 0. 50, optimally 0.25 ~0.45 at the pH range of 7 ~ 11; 3) BDM-KMnO4 extraction of gold from an oxide ore is similar to cyanide(cyanide-O2)extraction, but the leaching rate of gold by BDM-KMnO4 is faster than that by cyanide-O2; 4) gold may readily be recov-ered by carbon adsorption and zinc precipitation

  3. Mechanics, thermodynamics, and kinetics of ligand binding to biopolymers.

    Science.gov (United States)

    Jarillo, Javier; Morín, José A; Beltrán-Heredia, Elena; Villaluenga, Juan P G; Ibarra, Borja; Cao, Francisco J

    2017-01-01

    Ligands binding to polymers regulate polymer functions by changing their physical and chemical properties. This ligand regulation plays a key role in many biological processes. We propose here a model to explain the mechanical, thermodynamic, and kinetic properties of the process of binding of small ligands to long biopolymers. These properties can now be measured at the single molecule level using force spectroscopy techniques. Our model performs an effective decomposition of the ligand-polymer system on its covered and uncovered regions, showing that the elastic properties of the ligand-polymer depend explicitly on the ligand coverage of the polymer (i.e., the fraction of the polymer covered by the ligand). The equilibrium coverage that minimizes the free energy of the ligand-polymer system is computed as a function of the applied force. We show how ligands tune the mechanical properties of a polymer, in particular its length and stiffness, in a force dependent manner. In addition, it is shown how ligand binding can be regulated applying mechanical tension on the polymer. Moreover, the binding kinetics study shows that, in the case where the ligand binds and organizes the polymer in different modes, the binding process can present transient shortening or lengthening of the polymer, caused by changes in the relative coverage by the different ligand modes. Our model will be useful to understand ligand-binding regulation of biological processes, such as the metabolism of nucleic acid. In particular, this model allows estimating the coverage fraction and the ligand mode characteristics from the force extension curves of a ligand-polymer system.

  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. 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 p

  6. Protein-ligand binding affinity determination by the waterLOGSY method: An optimised approach considering ligand rebinding

    Science.gov (United States)

    Huang, Renjie; Bonnichon, Arnaud; Claridge, Timothy D. W.; Leung, Ivanhoe K. H.

    2017-03-01

    WaterLOGSY is a popular ligand-observed NMR technique to screen for protein-ligand interactions, yet when applied to measure dissociation constants (KD) through ligand titration, the results were found to be strongly dependent on sample conditions. Herein, we show that accurate KDs can be obtained by waterLOGSY with optimised experimental setup.

  7. 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

  8. The ligands of CXCR4 in vascularization

    OpenAIRE

    Tuchscheerer, Nancy

    2012-01-01

    The formation of a functional and integrated vascular network is a basic process in the growth and maintenance of tissues and can be established by two forms of blood vessel growth in adults: angiogenesis and arteriogenesis. In this study, the ligands of the chemokine receptor CXCR4 and its role in angiogenesis (represented by the experimental myocardial infarction) and arteriogenesis (represented by the murine hind limb ischemia model) was investigated. The first approach identified the CXCL...

  9. Dockomatic - automated ligand creation and docking

    OpenAIRE

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

    2010-01-01

    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 frie...

  10. 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.

  11. galectin-3 ligand — EDRN Public Portal

    Science.gov (United States)

    Galectin-3 is an endogenous lectin that binds glycan epitopes of cell membrane and some extracellular glycoproteins such as integrins and laminin. Galectin-3 is involved in several biological activities including regulation of cellular cycle, modulation of adhesion and tumor progression and metastasis. Serum galectin-3 ligands have been shown to modulate the immune reaction against tumors and viruses and their level increases in sera of several neoplastic diseases.

  12. RAGE and its ligands in retinal disease.

    Science.gov (United States)

    Barile, Gaetano R; Schmidt, Ann M

    2007-12-01

    RAGE, the receptor for advanced glycation endproducts (AGEs), is a multiligand signal transduction receptor of the immunoglobulin superfamily of cell surface molecules that has been implicated in the pathogenesis of diabetic complications, neurodegenerative diseases, inflammatory disorders, and cancer. These diverse biologic disorders reflect the multiplicity of ligands capable of cellular interaction via RAGE that include, in addition to AGEs, amyloid-beta (Abeta) peptide, the S100/calgranulin family of proinflammatory cytokines, and amphoterin, a member of the High Mobility Group Box (HMGB) DNA-binding proteins. In the retina, RAGE expression is present in neural cells, the vasculature, and RPE cells, and it has also been detected in pathologic cellular retinal responses including epiretinal and neovascular membrane formation. Ligands for RAGE, in particular AGEs, have emerged as relevant to the pathogenesis of diabetic retinopathy and age-related macular disease. While the understanding of RAGE and its role in retinal dysfunction with aging, diabetes mellitus, and/or activation of pro-inflammatory pathways is less complete compared to other organ systems, increasing evidence indicates that RAGE can initiate and sustain significant cellular perturbations in the inner and outer retina. For these reasons, antagonism of RAGE interactions with its ligands may be a worthwhile therapeutic target in such seemingly disparate, visually threatening retinal diseases as diabetic retinopathy, age-related macular degeneration, and proliferative vitreoretinopathy.

  13. EGF receptor ligands: recent advances [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Bhuminder Singh

    2016-09-01

    Full Text Available Seven ligands bind to and activate the mammalian epidermal growth factor (EGF receptor (EGFR/ERBB1/HER1: EGF, transforming growth factor-alpha (TGFA, heparin-binding EGF-like growth factor (HBEGF, betacellulin (BTC, amphiregulin (AREG, epiregulin (EREG, and epigen (EPGN. Of these, EGF, TGFA, HBEGF, and BTC are thought to be high-affinity ligands, whereas AREG, EREG, and EPGN constitute low-affinity ligands. This focused review is meant to highlight recent studies related to actions of the individual EGFR ligands, the interesting biology that has been uncovered, and relevant advances related to ligand interactions with the EGFR.

  14. EXPRESSION OF Fas LIGAND IN HUMAN COLON CANCER CELL LINES

    Institute of Scientific and Technical Information of China (English)

    张建军; 丁尔迅; 王强; 陈学云; 付志仁

    2001-01-01

    To investigate the expression of Fas ligand in human colon carcinoma cell lines. Methods: A total of six human colon cancer cell lines were examined for the expression of Fas ligand mRNA and cell surface protein by using RT-PCR and flow cytometry respectively. Results: The results showed that Fas ligand mRNA was expressed in all of the six cancer cell lines and Fas ligand cell surface protein was expressed in part of them. Conclusion: These data suggest that Fas ligand was expressed, at least in part, in human colon cancer cell lines and might facilitate to escape from immune surveillance of the host.

  15. The Recognition of Identical Ligands by Unrelated Proteins.

    Science.gov (United States)

    Barelier, Sarah; Sterling, Teague; O'Meara, Matthew J; Shoichet, Brian K

    2015-12-18

    The binding of drugs and reagents to off-targets is well-known. Whereas many off-targets are related to the primary target by sequence and fold, many ligands bind to unrelated pairs of proteins, and these are harder to anticipate. If the binding site in the off-target can be related to that of the primary target, this challenge resolves into aligning the two pockets. However, other cases are possible: the ligand might interact with entirely different residues and environments in the off-target, or wholly different ligand atoms may be implicated in the two complexes. To investigate these scenarios at atomic resolution, the structures of 59 ligands in 116 complexes (62 pairs in total), where the protein pairs were unrelated by fold but bound an identical ligand, were examined. In almost half of the pairs, the ligand interacted with unrelated residues in the two proteins (29 pairs), and in 14 of the pairs wholly different ligand moieties were implicated in each complex. Even in those 19 pairs of complexes that presented similar environments to the ligand, ligand superposition rarely resulted in the overlap of related residues. There appears to be no single pattern-matching "code" for identifying binding sites in unrelated proteins that bind identical ligands, though modeling suggests that there might be a limited number of different patterns that suffice to recognize different ligand functional groups.

  16. Full-electron ligand-to-ligand charge transfer in a compact Re(I) complex.

    Science.gov (United States)

    Yue, Yuankai; Grusenmeyer, Tod; Ma, Zheng; Zhang, Peng; Schmehl, Russell H; Beratan, David N; Rubtsov, Igor V

    2014-11-13

    Ligand-to-ligand charge transfer (LLCT) states in transition metal complexes are often characterized by fractional electron transfer due to coupling of the LLCT state with many other states via the metal. We designed and characterized a compact Re(I) complex that displays essentially full-electron charge transfer in the LLCT excited state. The complex, [Re(DCEB)(CO)3(L)](+) (DCEB = 4,4'-dicarboxyethyl-2,2'-bipyridine), referred to as ReEBA, features two redox active ligands with strong electron accepting (DCEB) and electron donating (L is 3-dimethylaminobenzonitrile (3DMABN)) properties. The lowest energy excited state formed with a ca. 10 ps time constant and was characterized as the full-electron 3DMABN → DCEB LLCT state using time-resolved infrared spectroscopy (TRIR), transient absorption spectroscopy, and DFT computations. Analysis of a range of vibrational modes helped to assign the charge transfer characteristics of the complex. The LLCT state lifetime in ReEBA shows a strong dependence on the solvent polarity and features solvent dependent frequency shifts for several vibrational reporters. The formation of a full-electron LLCT state (∼92%) was enabled by tuning the redox properties of the electron accepting ligand (DCEB) and simultaneously decoupling the redox active group of the electron donating ligand (3DMABN) from the metal center. This strategy is generally applicable for designing compact transition metal complexes that have full-electron LLCT states.

  17. Separation of tryptophan enantiomers by ligand-exchange chromatography with novel chiral ionic liquids ligand.

    Science.gov (United States)

    Qing, Haiqun; Jiang, Xinyu; Yu, Jingang

    2014-03-01

    Chiral ionic liquids (CILs) with amino acids as cations have been applied as novel chiral ligands coordinated with Cu(2+) to separate tryptophan enantiomers in ligand exchange chromatography. Four kinds of amino acid ionic liquids, including [L-Pro][CF3COO], [L-Pro][NO3], [L-Pro]2[SO4], and [L-Phe][CF3COO] were successfully synthesized and used for separation of tryptophan enantiomers. To optimize the separation conditions, [L-Pro][CF3COO] was selected as the model ligand. Some factors influencing the efficiency of chiral separation, such as copper ion concentration, CILs concentration, methanol ratio (methanol/H2O, v/v), and pH, were investigated. The obtained optimal separation conditions were as follows: 8.0 mmol/L Cu(OAc)2, 4.0 mmol/L [L-Pro][CF3COO], and 20% (v/v) methanol at pH 3.6. Under the optimum conditions, acceptable enantioseparation of tryptophan enantiomers could be observed with a resolution of 1.89. The results demonstrate the good applicability of CILs with amino acids as cations for chiral separation. Furthermore, a comparative study was also conducted for exploring the mechanism of the CILs as new ligands in ligand exchange chromatography. © 2014 Wiley Periodicals, Inc.

  18. Two Triazole-Based Phosphine Ligands Prepared via Temperature-Mediated Li/H Exchange: Cu(I) and Au(I) Complexes and Structural Studies.

    Science.gov (United States)

    Choubey, Bimba; Radhakrishna, Latchupatula; Mague, Joel T; Balakrishna, Maravanji S

    2016-09-06

    The kinetically favored triazole-based phosphine 1-(2-(diphenylphosphino)phenyl)-4-phenyl-1H-1,2,3-triazole (2, L1) and its thermodynamically preferred isomer, 5-(diphenylphosphino)-1,4-diphenyl-1H-1,2,3-triazole (3, L2), were obtained by the temperature-controlled lithiation of 2-bromotriazole followed by the reaction with chlorodiphenylphosphine. The structures of phosphines 2 and 3 were determined by X-ray diffraction. Upon reaction with late transition-metal derivatives (Cu(I), Ag(I), and Au(I)), phosphines 2 and 3 form complexes with monodentate (Cu(I), Ag(I), and Au(I); κ(1)-P), chelate (Cu(I); κ(2)-P,N), bridged bidentate (Cu(I); μ(2)-P,N), and tridentate (Cu(I); μ(2),κ(2)-P,N,N) modes of coordination. Reactions with copper(I) halides produced mono-, di-, and tetranuclear complexes, whereas the reaction of 2 with [Cu(NCCH3)4]BF4 yielded the binuclear complex [Cu2(CH3CN)2{o-Ph2P(C6H4){1,2,3-N3C(Ph)C(H)}-μ-(κ-P,κ-N),κ-N}2](BF4)2 (10) with the ligand acting as a six-electron donor involving phosphorus and two triazole nitrogen atoms. The copper complexes of 2 and 3 containing rhomboid Cu2X2 units, [(Cu)2(μ-X)2{o-Ph2P(C6H4){1,2,3-N3C(Ph)C(H)}-κ-P}2] (4, X = Cl; 5, X = Br), on treatment with 1,10-phenanthroline and 2,2'-bipyridine gave mixed-ligand complexes of the type [(CuX)(N∩N-κ(2)-N,N){o-Ph2P(C6H4){1,2,3-N3C(Ph)C(H)}-κ-P}] (N∩N = 1,10-phen and 2,2'-bipy; X = Cl, Br, and I).

  19. 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

    indicate that channel opening is accompanied by conformational rearrangements in both beta-sheets. In an attempt to resolve ligand-dependent movements in the ligand-binding domain, we employed voltage-clamp fluorometry on alpha1 glycine receptors to compare changes mediated by the agonist, glycine......, 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...

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    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...... 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...... characteristics as calreticulin's interaction with C1q and MBL: a time-dependent saturable binding to immobilized protein, which was initially sensitive to salt but gradually developed into a salt-insensitive interaction. Thus, the interaction requires a structural change in the interaction partner and leads...

  1. Evaluation of small ligand-protein interaction by ligation reaction with DNA-modified ligand.

    Science.gov (United States)

    Sugita, Rie; Mie, Masayasu; Funabashi, Hisakage; Kobatake, Eiry

    2010-01-01

    A method for the evaluation of interactions between protein and ligand using DNA-modified ligands, including signal enhancement of the DNA ligation reactions, is described. For proof of principle, a DNA probe modified by biotin was used. Two DNA probes were prepared with complementary sticky-ends. While one DNA probe was modified at the 5'-end of the sticky-end, the other was not modified. The probes could be ligated together by T4 DNA ligase along the strand without biotin modification. However, in the presence of streptavidin or anti-biotin Fab, the ligation reaction joining the two probes could not occur on either strand.

  2. Landscape of protein-small ligand binding modes.

    Science.gov (United States)

    Kasahara, Kota; Kinoshita, Kengo

    2016-09-01

    Elucidating the mechanisms of specific small-molecule (ligand) recognition by proteins is a long-standing conundrum. While the structures of these molecules, proteins and ligands, have been extensively studied, protein-ligand interactions, or binding modes, have not been comprehensively analyzed. Although methods for assessing similarities of binding site structures have been extensively developed, the methods for the computational treatment of binding modes have not been well established. Here, we developed a computational method for encoding the information about binding modes as graphs, and assessing their similarities. An all-against-all comparison of 20,040 protein-ligand complexes provided the landscape of the protein-ligand binding modes and its relationships with protein- and chemical spaces. While similar proteins in the same SCOP Family tend to bind relatively similar ligands with similar binding modes, the correlation between ligand and binding similarities was not very high (R(2)  = 0.443). We found many pairs with novel relationships, in which two evolutionally distant proteins recognize dissimilar ligands by similar binding modes (757,474 pairs out of 200,790,780 pairs were categorized into this relationship, in our dataset). In addition, there were an abundance of pairs of homologous proteins binding to similar ligands with different binding modes (68,217 pairs). Our results showed that many interesting relationships between protein-ligand complexes are still hidden in the structure database, and our new method for assessing binding mode similarities is effective to find them.

  3. Integrin receptors and ligand-gated channels.

    Science.gov (United States)

    Morini, Raffaella; Becchetti, Andrea

    2010-01-01

    Plastic expression of different integrin subunits controls the different stages of neural development, whereas in the adult integrins regulate synaptic stability. Evidence of integrin-channel crosstalk exists for ionotropic glutamate receptors. As is often the case in other tissues, integrin engagement regulates channel activity through complex signaling pathways that often include tyrosine phosphorylation cascades. The specific pathways recruited by integrin activation depend on cerebral region and cell type. In turn, ion channels control integrin expression onto the plasma membrane and their ligand binding affinity. The most extensive studies concern the hippocampus and suggest implications for neuronal circuit plasticity. The physiological relevance of these findings depends on whether adhesion molecules, aside from determining tissue stability, contribute to synaptogenesis and the responsiveness of mature synapses, thus contributing to long-term circuit consolidation. Little evidence is available for other ligand-gated channels, with the exception of nicotinic receptors. These exert a variety of functions in neurons and non neural tissue, both in development and in the adult, by regulating cell cycle, synaptogenesis and synaptic circuit refinement. Detailed studies in epidermal keratinocytes have shed some light on the possible mechanisms through which ACh can regulate cell motility, which may be of general relevance for morphogenetic processes. As to the control of mature synapses, most results concern the integrinic control of nicotinic receptors in the neuromuscular junction. Following this lead, a few studies have addressed similar topics in adult cerebral synapses. However, pursuing and interpreting these results in the brain is especially difficult because of the complexity of the nicotinic roles and the widespread contribution of nonsynaptic, paracrine transmission. From a pathological point of view, considering the well-known contribution of both

  4. Polydentate cyclotriphosphazene ligands: Design, synthesis and bioactivity

    Institute of Scientific and Technical Information of China (English)

    Le Wang; Yong Ye; Shang Bin Zhong; Yu Fen Zhao

    2009-01-01

    Five multinuelear cyclotriphosphazene ligands were synthesized and tested for their cleavage activities to plasmid DNA. All of these new compounds were confirmed by MS, 1H NMR, 31p NMR, 13C NMR and IR. Preliminary studies on the cleavage of pUC19 DNA in the presence of metal complexes were performed. The results revealed that these complexes could act as powerful catalysts under physiological conditions. The complexes 3b + Cu can effectively cleave DNA to nicked form, giving hydrolysis rate constant of 0.08/h under physiological conditions. An acid-base catalyzed DNA phosphate-diester hydrolysis mechanism was also proposed.

  5. Thermal melting studies of ligand DNA interactions.

    Science.gov (United States)

    Guédin, Aurore; Lacroix, Laurent; Mergny, Jean-Louis

    2010-01-01

    A simple thermal melting experiment may be used to demonstrate the stabilization of a given structure by a ligand (usually a small molecule, sometimes a peptide). Preparation of the sample is straightforward, and the experiment itself requires an inexpensive apparatus. Furthermore, reasonably low amounts of sample are required. A qualitative analysis of the data is simple: An increase in the melting temperature (T(m)) indicates preferential binding to the folded form as compared to the unfolded form. However, it is perilous to derive an affinity constant from an increase in T(m) as other factors play a role.

  6. Computer-aided design of GPCR ligands.

    Science.gov (United States)

    Gutiérrez-de-Terán, Hugo; Keränen, Henrik; Azuaje, Jhonny; Rodríguez, David; Åqvist, Johan; Sotelo, Eddy

    2015-01-01

    The recent availability of several GPCR crystal structures now contributes decisively to the perspective of structure-based ligand design. In this context, computational approaches are extremely helpful, particularly if properly integrated in drug design projects with cooperation between computational and medicinal chemistry teams. Here, we present the pipelines used in one such project, devoted to the design of novel potent and selective antagonists for the different adenosine receptors. The details of the computational strategies are described, and particular attention is given to explain how these procedures can effectively guide the synthesis of novel chemical entities.

  7. The autoxidation activity of new mixed-ligand manganese and iron complexes with tripodal ligands

    NARCIS (Netherlands)

    van Gorkum, R.; Berding, J.; Tooke, D.M.; Spek, A.L.; Reedijk, J.; Bouwman, E.

    2007-01-01

    The activity of new manganese and iron complexes of dianionic tripodal ligands in the autoxidation of ethyl linoleate (EL) is reported. EL consumption rates were monitored using time-resolved FTIR and the degree of oligomerisation was determined by SEC. Almost all complexes showed the same trend in

  8. Ligand binding by the tandem glycine riboswitch depends on aptamer dimerization but not double ligand occupancy.

    Science.gov (United States)

    Ruff, Karen M; Strobel, Scott A

    2014-11-01

    The glycine riboswitch predominantly exists as a tandem structure, with two adjacent, homologous ligand-binding domains (aptamers), followed by a single expression platform. The recent identification of a leader helix, the inclusion of which eliminates cooperativity between the aptamers, has reopened the debate over the purpose of the tandem structure of the glycine riboswitch. An equilibrium dialysis-based assay was combined with binding-site mutations to monitor glycine binding in each ligand-binding site independently to understand the role of each aptamer in glycine binding and riboswitch tertiary interactions. A series of mutations disrupting the dimer interface was used to probe how dimerization impacts ligand binding by the tandem glycine riboswitch. While the wild-type tandem riboswitch binds two glycine equivalents, one for each aptamer, both individual aptamers are capable of binding glycine when the other aptamer is unoccupied. Intriguingly, glycine binding by aptamer-1 is more sensitive to dimerization than glycine binding by aptamer-2 in the context of the tandem riboswitch. However, monomeric aptamer-2 shows dramatically weakened glycine-binding affinity. In addition, dimerization of the two aptamers in trans is dependent on glycine binding in at least one aptamer. We propose a revised model for tandem riboswitch function that is consistent with these results, wherein ligand binding in aptamer-1 is linked to aptamer dimerization and stabilizes the P1 stem of aptamer-2, which controls the expression platform.

  9. SuperLigands – a database of ligand structures derived from the Protein Data Bank

    Directory of Open Access Journals (Sweden)

    Preissner Robert

    2005-05-01

    Full Text Available Abstract Background Currently, the PDB contains approximately 29,000 protein structures comprising over 70,000 experimentally determined three-dimensional structures of over 5,000 different low molecular weight compounds. Information about these PDB ligands can be very helpful in the field of molecular modelling and prediction, particularly for the prediction of protein binding sites and function. Description Here we present an Internet accessible database delivering PDB ligands in the MDL Mol file format which, in contrast to the PDB format, includes information about bond types. Structural similarity of the compounds can be detected by calculation of Tanimoto coefficients and by three-dimensional superposition. Topological similarity of PDB ligands to known drugs can be assessed via Tanimoto coefficients. Conclusion SuperLigands supplements the set of existing resources of information about small molecules bound to PDB structures. Allowing for three-dimensional comparison of the compounds as a novel feature, this database represents a valuable means of analysis and prediction in the field of biological and medical research.

  10. SuperLigands – a database of ligand structures derived from the Protein Data Bank

    Science.gov (United States)

    Michalsky, Elke; Dunkel, Mathias; Goede, Andrean; Preissner, Robert

    2005-01-01

    Background Currently, the PDB contains approximately 29,000 protein structures comprising over 70,000 experimentally determined three-dimensional structures of over 5,000 different low molecular weight compounds. Information about these PDB ligands can be very helpful in the field of molecular modelling and prediction, particularly for the prediction of protein binding sites and function. Description Here we present an Internet accessible database delivering PDB ligands in the MDL Mol file format which, in contrast to the PDB format, includes information about bond types. Structural similarity of the compounds can be detected by calculation of Tanimoto coefficients and by three-dimensional superposition. Topological similarity of PDB ligands to known drugs can be assessed via Tanimoto coefficients. Conclusion SuperLigands supplements the set of existing resources of information about small molecules bound to PDB structures. Allowing for three-dimensional comparison of the compounds as a novel feature, this database represents a valuable means of analysis and prediction in the field of biological and medical research. PMID:15943884

  11. 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.

  12. Increased accuracy of ligand sensing by receptor internalization

    CERN Document Server

    Aquino, Gerardo

    2010-01-01

    Many types of cells can sense external ligand concentrations with cell-surface receptors at extremely high accuracy. Interestingly, ligand-bound receptors are often internalized, a process also known as receptor-mediated endocytosis. While internalization is involved in a vast number of important functions for the life of a cell, it was recently also suggested to increase the accuracy of sensing ligand as the overcounting of the same ligand molecules is reduced. Here we show, by extending simple ligand-receptor models to out-of-equilibrium thermodynamics, that internalization increases the accuracy with which cells can measure ligand concentrations in the external environment. Comparison with experimental rates of real receptors demonstrates that our model has indeed biological significance.

  13. 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.

  14. Ligands of Therapeutic Utility for the Liver X Receptors

    Directory of Open Access Journals (Sweden)

    Rajesh Komati

    2017-01-01

    Full Text Available Liver X receptors (LXRs have been increasingly recognized as a potential therapeutic target to treat pathological conditions ranging from vascular and metabolic diseases, neurological degeneration, to cancers that are driven by lipid metabolism. Amidst intensifying efforts to discover ligands that act through LXRs to achieve the sought-after pharmacological outcomes, several lead compounds are already being tested in clinical trials for a variety of disease interventions. While more potent and selective LXR ligands continue to emerge from screening of small molecule libraries, rational design, and empirical medicinal chemistry approaches, challenges remain in minimizing undesirable effects of LXR activation on lipid metabolism. This review provides a summary of known endogenous, naturally occurring, and synthetic ligands. The review also offers considerations from a molecular modeling perspective with which to design more specific LXRβ ligands based on the interaction energies of ligands and the important amino acid residues in the LXRβ ligand binding domain.

  15. 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.

  16. Do organic ligands affect calcite dissolution rates?

    Science.gov (United States)

    Oelkers, Eric H.; Golubev, Sergey V.; Pokrovsky, Oleg S.; Bénézeth, Pascale

    2011-04-01

    Steady state Iceland-spar calcite dissolution rates were measured at 25 °C in aqueous solutions containing 0.1 M NaCl and up to 0.05 M dissolved bicarbonate at pH from 7.9 to 9.1 in the presence of 13 distinct dissolved organic ligands in mixed-flow reactors. The organic ligands considered in this study include those most likely to be present in either (1) aquifers at the conditions pertinent to CO 2 sequestration or (2) soil/early diagenetic environments: acetate, phthalate, citrate, EDTA 4-, succinate, D-glucosaminate, L-glutamate, D-gluconate, 2,4-dihydroxybenzoate, 3,4-dihydroxybenzoate, fumarate, malonate, and gallate. Results show that the presence of extract, humic acid, pectin, and gum xanthan. In no case did the presence of <100 ppm of these organics change calcite dissolution rates by more than a factor of 2.5. Results obtained in this study suggest that the presence of aqueous organic anions negligibly affects calcite forward dissolution rates in most natural environments. Some effect on calcite reactivity may be observed, however, by the presence of organic anions if they change substantially the chemical affinity of the fluid with respect to calcite.

  17. Continuous microfluidic assortment of interactive ligands (CMAIL)

    Science.gov (United States)

    Hsiao, Yi-Hsing; Huang, Chao-Yang; Hu, Chih-Yung; Wu, Yen-Yu; Wu, Chung-Hsiun; Hsu, Chia-Hsien; Chen, Chihchen

    2016-08-01

    Finding an interactive ligand-receptor pair is crucial to many applications, including the development of monoclonal antibodies. Biopanning, a commonly used technique for affinity screening, involves a series of washing steps and is lengthy and tedious. Here we present an approach termed continuous microfluidic assortment of interactive ligands, or CMAIL, for the screening and sorting of antigen-binding single-chain variable antibody fragments (scFv) displayed on bacteriophages (phages). Phages carrying native negative charges on their coat proteins were electrophoresed through a hydrogel matrix functionalized with target antigens under two alternating orthogonal electric fields. During the weak horizontal electric field phase, phages were differentially swept laterally depending on their affinity for the antigen, and all phages were electrophoresed down to be collected during the strong vertical electric field phase. Phages of different affinity were spatially separated, allowing the continuous operation. More than 105 CFU (colony forming unit) antigen-interacting phages were isolated with ~100% specificity from a phage library containing 3 × 109 individual members within 40 minutes of sorting using CMAIL. CMAIL is rapid, sensitive, specific, and does not employ washing, elution or magnetic beads. In conclusion, we have developed an efficient and cost-effective method for isolating and sorting affinity reagents involving phage display.

  18. Quantifying Rosette Formation Mediated by Receptor-ligand Interactions

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    1 IntroductionRosetting is a simple assay for specific cell-cell adhesion, in which receptor- (or ligand-) coated RBCs form the rosettes with ligand- (or receptor-) expressed nucleated cells~([1]). Although routinely used by immunologists to examine the functionality of the interacting receptors and ligands, however, it has not been regarded as a quantitative method, as the measured rosette fraction has not been quantitatively related to the underlying molecular properties.Recently, we have solved probabili...

  19. Chemometric analysis of ligand receptor complementarity: identifying Complementary Ligands Based on Receptor Information (CoLiBRI).

    Science.gov (United States)

    Oloff, Scott; Zhang, Shuxing; Sukumar, Nagamani; Breneman, Curt; Tropsha, Alexander

    2006-01-01

    We have developed a novel structure-based chemoinformatics approach to search for Complimentary Ligands Based on Receptor Information (CoLiBRI). CoLiBRI is based on the representation of both receptor binding sites and their respective ligands in a space of universal chemical descriptors. The binding site atoms involved in the interaction with ligands are identified by the means of a computational geometry technique known as Delaunay tessellation as applied to X-ray characterized ligand-receptor complexes. TAE/RECON multiple chemical descriptors are calculated independently for each ligand as well as for its active site atoms. The representation of both ligands and active sites using chemical descriptors allows the application of well-known chemometric techniques in order to correlate chemical similarities between active sites and their respective ligands. We have established a protocol to map patterns of nearest neighbor active site vectors in a multidimensional TAE/RECON space onto those of their complementary ligands and vice versa. This protocol affords the prediction of a virtual complementary ligand vector in the ligand chemical space from the position of a known active site vector. This prediction is followed by chemical similarity calculations between this virtual ligand vector and those calculated for molecules in a chemical database to identify real compounds most similar to the virtual ligand. Consequently, the knowledge of the receptor active site structure affords straightforward and efficient identification of its complementary ligands in large databases of chemical compounds using rapid chemical similarity searches. Conversely, starting from the ligand chemical structure, one may identify possible complementary receptor cavities as well. We have applied the CoLiBRI approach to a data set of 800 X-ray characterized ligand-receptor complexes in the PDBbind database. Using a k nearest neighbor (kNN) pattern recognition approach and variable selection

  20. Riboswitch Structure: an Internal Residue Mimicking the Purine Ligand

    Energy Technology Data Exchange (ETDEWEB)

    Delfosse, V.; Bouchard, P; Bonneau, E; Dagenais, P; Lemay, J; Lafontaine, D; Legault, P

    2009-01-01

    The adenine and guanine riboswitches regulate gene expression in response to their purine ligand. X-ray structures of the aptamer moiety of these riboswitches are characterized by a compact fold in which the ligand forms a Watson-Crick base pair with residue 65. Phylogenetic analyses revealed a strict restriction at position 39 of the aptamer that prevents the G39-C65 and A39-U65 combinations, and mutational studies indicate that aptamers with these sequence combinations are impaired for ligand binding. In order to investigate the rationale for sequence conservation at residue 39, structural characterization of the U65C mutant from Bacillus subtilis pbuE adenine riboswitch aptamer was undertaken. NMR spectroscopy and X-ray crystallography studies demonstrate that the U65C mutant adopts a compact ligand-free structure, in which G39 occupies the ligand-binding site of purine riboswitch aptamers. These studies present a remarkable example of a mutant RNA aptamer that adopts a native-like fold by means of ligand mimicking and explain why this mutant is impaired for ligand binding. Furthermore, this work provides a specific insight into how the natural sequence has evolved through selection of nucleotide identities that contribute to formation of the ligand-bound state, but ensures that the ligand-free state remains in an active conformation.

  1. Competitive antagonism of AMPA receptors by ligands of different classes

    DEFF Research Database (Denmark)

    Hogner, Anders; Greenwood, Jeremy R; Liljefors, Tommy

    2003-01-01

    that ATPO and DNQX stabilize an open form of the ligand-binding core by different sets of interactions. Computational techniques are used to quantify the differences between these two ligands and to map the binding site. The isoxazole moiety of ATPO acts primarily as a spacer, and other scaffolds could......-(phosphonomethoxy)-4-isoxazolyl]propionic acid (ATPO) in complex with the ligand-binding core of the receptor. Comparison with the only previous structure of the ligand-binding core in complex with an antagonist, 6,7-dinitro-2,3-quinoxalinedione (DNQX) (Armstrong, N.; Gouaux, E. Neuron 2000, 28, 165-181), reveals...

  2. Design of targeting ligands in medicinal inorganic chemistry.

    Science.gov (United States)

    Storr, Tim; Thompson, Katherine H; Orvig, Chris

    2006-06-01

    This tutorial review will highlight recent advances in medicinal inorganic chemistry pertaining to the use of multifunctional ligands for enhanced effect. Ligands that adequately bind metal ions and also include specific targeting features are gaining in popularity due to their ability to enhance the efficacy of less complicated metal-based agents. Moving beyond the traditional view of ligands modifying reactivity, stabilizing specific oxidation states, and contributing to substitution inertness, we will discuss recent work involving metal complexes with multifunctional ligands that target specific tissues, membrane receptors, or endogenous molecules, including enzymes.

  3. Structural basis for ligand recognition of incretin receptors

    DEFF Research Database (Denmark)

    Underwood, Christina Rye; Parthier, Christoph; Reedtz-Runge, Steffen

    2010-01-01

    been solved recently by X-ray crystallography. The crystal structures reveal a similar fold of the ECD and a similar mechanism of ligand binding, where the ligand adopts an α-helical conformation. Residues in the C-terminal part of the ligand interact directly with the ECD and hydrophobic interactions...... appear to be the main driving force for ligand binding to the ECD of incretin receptors. Obviously, the-still missing-structures of full-length incretin receptors are required to construct a complete picture of receptor function at the molecular level. However, the progress made recently in structural...

  4. Superior serum half life of albumin tagged TNF ligands

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Nicole [Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Wuerzburg, Roentgenring 11, 97070 Wuerzburg (Germany); Schneider, Britta; Pfizenmaier, Klaus [Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart (Germany); Wajant, Harald, E-mail: harald.wajant@mail.uni-wuerzburg.de [Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Wuerzburg, Roentgenring 11, 97070 Wuerzburg (Germany)

    2010-06-11

    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.

  5. Ultrafast heme-ligand recombination in truncated hemoglobin HbO from Mycobacterium tuberculosis: A ligand cage

    Science.gov (United States)

    Jasaitis, Audrius; Ouellet, Hugues; Lambry, Jean-Christophe; Martin, Jean-Louis; Friedman, Joel M.; Guertin, Michel; Vos, Marten H.

    2012-03-01

    Truncated hemoglobin HbO from Mycobacterium tuberculosis displays very slow exchange of diatomic ligands with its environment. Using femtosecond spectroscopy, we show that upon photoexcitation, ligands rebind with unusual speed and efficiency. Only ˜1% O2 can escape from the heme pocket and less than 1% NO. Most remarkably, CO rebinding occurs for 95%, predominantly in 1.2 ns. The general CO rebinding properties are unexpectedly robust against changes in the interactions with close by aromatic residues Trp88 (G8) and Tyr36 (CD1). Molecular dynamics simulations of the CO complex suggest that interactions of the ligand with structural water molecules as well as its rotational freedom play a role in the high reactivity of the ligand and the heme. The slow exchange of ligands between heme and environment may result from a combination of hindered ligand access to the heme pocket by the network of distal aromatic residues, and low escape probability from the pocket.

  6. Design of Ligands for Affinity Purification of G-CSF Based on Peptide Ligands Derived from a Peptide Library

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Combinatorial peptide libraries have become powerful tools to screen functional ligands by the principle of affinity selection. We screened in a phage peptide library to investigate potential peptide affinity ligands for the purification of human granulocyte colony-stimulation factor(hG-CSF). Peptide ligands will be promising to replace monoclonal antibodies as they have advantages of high stability, efficiency, selectivity and low price.

  7. Ligand "Brackets" for Ga-Ga Bond.

    Science.gov (United States)

    Fedushkin, Igor L; Skatova, Alexandra A; Dodonov, Vladimir A; Yang, Xiao-Juan; Chudakova, Valentina A; Piskunov, Alexander V; Demeshko, Serhiy; Baranov, Evgeny V

    2016-09-06

    The reactivity of digallane (dpp-Bian)Ga-Ga(dpp-Bian) (1) (dpp-Bian = 1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene) toward acenaphthenequinone (AcQ), sulfur dioxide, and azobenzene was investigated. The reaction of 1 with AcQ in 1:1 molar ratio proceeds via two-electron reduction of AcQ to give (dpp-Bian)Ga(μ2-AcQ)Ga(dpp-Bian) (2), in which diolate [AcQ](2-) acts as "bracket" for the Ga-Ga bond. The interaction of 1 with AcQ in 1:2 molar ratio proceeds with an oxidation of the both dpp-Bian ligands as well as of the Ga-Ga bond to give (dpp-Bian)Ga(μ2-AcQ)2Ga(dpp-Bian) (3). At 330 K in toluene complex 2 decomposes to give compounds 3 and 1. The reaction of complex 2 with atmospheric oxygen results in oxidation of a Ga-Ga bond and affords (dpp-Bian)Ga(μ2-AcQ)(μ2-O)Ga(dpp-Bian) (4). The reaction of digallane 1 with SO2 produces, depending on the ratio (1:2 or 1:4), dithionites (dpp-Bian)Ga(μ2-O2S-SO2)Ga(dpp-Bian) (5) and (dpp-Bian)Ga(μ2-O2S-SO2)2Ga(dpp-Bian) (6). In compound 5 the Ga-Ga bond is preserved and supported by dithionite dianionic bracket. In compound 6 the gallium centers are bridged by two dithionite ligands. Both 5 and 6 consist of dpp-Bian radical anionic ligands. Four-electron reduction of azobenzene with 1 mol equiv of digallane 1 leads to complex (dpp-Bian)Ga(μ2-NPh)2Ga(dpp-Bian) (7). Paramagnetic compounds 2-7 were characterized by electron spin resonance spectroscopy, and their molecular structures were established by single-crystal X-ray analysis. Magnetic behavior of compounds 2, 5, and 6 was investigated by superconducting quantum interference device technique in the range of 2-295 K.

  8. Characterizing mixed phosphonic acid ligand capping on CdSe/ZnS quantum dots using ligand exchange and NMR spectroscopy.

    Science.gov (United States)

    Davidowski, Stephen K; Lisowski, Carmen E; Yarger, Jeffery L

    2016-03-01

    The ligand capping of phosphonic acid functionalized CdSe/ZnS core-shell quantum dots (QDs) was investigated with a combination of solution and solid-state (31) P nuclear magnetic resonance (NMR) spectroscopy. Two phosphonic acid ligands were used in the synthesis of the QDs, tetradecylphosphonic acid and ethylphosphonic acid. Both alkyl phosphonic acids showed broad liquid and solid-state (31) P NMR resonances for the bound ligands, indicative of heterogeneous binding to the QD surface. In order to quantify the two ligand populations on the surface, ligand exchange facilitated by phenylphosphonic acid resulted in the displacement of the ethylphosphonic acid and tetradecylphosphonic acid and allowed for quantification of the free ligands using (31) P liquid-state NMR. After washing away the free ligand, two broad resonances were observed in the liquids' (31) P NMR corresponding to the alkyl and aromatic phosphonic acids. The washed samples were analyzed via solid-state (31) P NMR, which confirmed the ligand populations on the surface following the ligand exchange process. Copyright © 2015 John Wiley & Sons, Ltd.

  9. Phosphinothiolates as ligands for polyhydrido copper nanoclusters.

    Science.gov (United States)

    Huertos, Miguel A; Cano, Israel; Bandeira, Nuno A G; Benet-Buchholz, Jordi; Bo, Carles; van Leeuwen, Piet W N M

    2014-12-01

    The reaction of [CuI(HSC6 H4 PPh2 )]2 with NaBH4 in CH2 Cl2 /EtOH led to air- and moisture-stable copper hydride nanoparticles (CuNPs) containing phosphinothiolates as new ligands, one of which was isolated by crystallization. The X-ray crystal structure of [Cu18 H7 L10 I] (L=(-) S(C6 H4 )PPh2 ) shows unprecedented features in its 28-atom framework (18 Cu and 10 S atoms). Seven hydrogen atoms, in hydride form, are needed for charge balance and were located by density functional theory methods. H2 was released from the copper hydride nanoparticles by thermolysis and visible light irradiation.

  10. Trinuclear manganese complexes of unsymmetrical polypodal diamino N3O3 ligands with an unusual [Mn3(μ-OR)4]5+ triangular core: synthesis, characterization, and catalase activity.

    Science.gov (United States)

    Ledesma, Gabriela N; Anxolabéhère-Mallart, Elodie; Rivière, Eric; Mallet-Ladeira, Sonia; Hureau, Christelle; Signorella, Sandra R

    2014-03-01

    Two new tri-Mn(III) complexes of general formula [Mn3L2(μ-OH)(OAc)]ClO4 (H3L = 1-[N-(2-pyridylmethyl),N-(2-hydroxybenzyl)amino]-3-[N'-(2-hydroxybenzyl),N'-(4-X-benzyl)amino]propan-2-ol; 1ClO4, X = Me; 2ClO4, X = H) have been prepared and characterized. X-ray diffraction analysis of 1ClO4 reveals that the complex cation possesses a Mn3(μ-alkoxo)2(μ-hydroxo)(μ-phenoxo)(4+) core, with the three Mn atoms bound to two fully deprotonated N3O3 chelating L(3-), one exogenous acetato ligand, and one hydroxo bridge, the structure of which is retained upon dissolution in acetonitrile or methanol. The three Mn atoms occupy the vertices of a nearly isosceles triangle (Mn1···Mn3 = 3.6374(12) Å, Mn2···Mn3 3.5583(13) Å, and Mn1···Mn2 3.2400(12) Å), with one substitution-labile site on the apical Mn ion occupied by terminally bound monodentate acetate. Temperature-dependent magnetic susceptibility studies indicate the presence of predominant antiferromagnetic intramolecular interactions between Mn(III) ions in 1ClO4. Complexes 1ClO4 and 2ClO4 decompose H2O2 at comparable rates upon initial binding of peroxide through acetate substitution, with retention of core structure during catalysis. Kinetic and spectroscopic studies suggest that these complexes employ the [Mn-(μ-oxo/aquo)-Mn](4+) moiety to activate peroxide, with the additional (μ-alkoxo)(μ-phenoxo)Mn(μ-alkoxo) metallobridge carrying out a structural function.

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

    African Journals Online (AJOL)

    Erah

    Methods: The method is based on ligand-exchange reaction. ... Clonazepam, Ligand-exchange reaction, Kinetic spectrometry, Validation, Pharmaceutical ... sensitive and selective analytical method for ... does not need sophisticated instruments or ..... of clonazepam in human serum ("Lytorol N) by standard addition method.

  12. 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.

  13. Functionalized pyrazines as ligands for minor actinide extraction and catalysis

    NARCIS (Netherlands)

    Nikishkin, N.

    2013-01-01

    The research presented in this thesis concerns the design of ligands for a wide range of applications, from nuclear waste treatment to catalysis. The strategies employed to design actinide-selective extractants, for instance, comprise the fine tuning of the ligand electronic properties as well as

  14. a review of cyclopentadienyl type ligands in group 4 metallocene ...

    African Journals Online (AJOL)

    Neil Grimmer

    metal, ligand and bridge choice has on polymerisation activity and the physical properties of the polymer ... It is the ligands bonded to a metal atom(s) that strongly influence the course of a ...... The indenyl framework also lends itself to .... capable of producing an amorphous polymer.151,162 The reason is proposed to relate.

  15. Soluble CD40 ligand in acute coronary syndromes

    NARCIS (Netherlands)

    C. Heeschen (Christopher); S. Dimmeler (Stefanie); C.W. Hamm (Christian); A.M. Zeiher (Andreas); M.L. Simoons (Maarten); M.J.B.M. van den Brand (Marcel); H. Boersma (Eric)

    2003-01-01

    textabstractBACKGROUND: CD40 ligand is expressed on platelets and released from them on activation. We investigated the predictive value of soluble CD40 ligand as a marker for clinical outcome and the therapeutic effect of glycoprotein IIb/IIIa receptor inhibition in patients with acute coronary syn

  16. Functionalized pyrazines as ligands for minor actinide extraction and catalysis

    NARCIS (Netherlands)

    Nikishkin, N.

    2013-01-01

    The research presented in this thesis concerns the design of ligands for a wide range of applications, from nuclear waste treatment to catalysis. The strategies employed to design actinide-selective extractants, for instance, comprise the fine tuning of the ligand electronic properties as well as us

  17. 1,8-Dimethylnaphthalene-bridged diphosphine ligands

    DEFF Research Database (Denmark)

    Bellabarba, Ronan M; Hammond, Colin; Forman, Grant S

    2006-01-01

    The synthesis of a new series of ligands with a 1,8-dimethylnaphthalene backbone is reported, 1,8-(R2PCH2)2C10H6, where R = (t)Bu 1 (dbpn), (i)Pr 2 (dippn), Cy 3 (dchpn) and Ph 4 (dphpn). The ligand 1 is structurally characterised by X-ray crystallography. A comparative structural study...

  18. Dynamic Ligand Reactivity in a Rhodium Pincer Complex

    NARCIS (Netherlands)

    Tang, Zhou; Otten, Edwin; Reek, Joost N H; van der Vlugt, Jarl Ivar; de Bruin, Bas

    2015-01-01

    Ligand cooperativity provides (transition) metal complexes with new reactivities in substrate activation and catalytic reactions, but usually the ligand acts as an internal (Brønsted) base, while the metal acts as a (Lewis) acid. We describe the synthesis and stepwise activation of a new phosphane-p

  19. Ligand-modified metal clusters for gas separation and purification

    Energy Technology Data Exchange (ETDEWEB)

    Okrut, Alexander; Ouyang, Xiaoying; Runnebaum, Ron; Gates, Bruce C.; Katz, Alexander

    2017-02-21

    Provided is an organic ligand-bound metal surface that selects one gaseous species over another. The species can be closely sized molecular species having less than 1 Angstrom difference in kinetic diameter. In one embodiment, the species comprise carbon monoxide and ethylene. Such organic ligand-bound metal surfaces can be successfully used in gas phase separations or purifications, sensing, and in catalysis.

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

    Science.gov (United States)

    Duus, K; Pagh, R T; Holmskov, U; Højrup, P; Skov, S; Houen, G

    2007-11-01

    The molecular chaperone calreticulin has been shown to bind C1q and mannan-binding lectin (MBL), which are constituents of the innate immune defence system. C1q and MBL do not share a large sequence identity but have a similar overall molecular architecture: an N-terminal triple-helical collagen-like domain and a C-terminal globular domain with ligand-binding properties. C1q is a hetero-trimer, while MBL is a homo-trimer, but due to the presence of N-terminal cysteines they both form higher order oligomers of trimers, which are the mature functional molecules. The same molecular architecture 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 characteristics as calreticulin's interaction with C1q and MBL: a time-dependent saturable binding to immobilized protein, which was initially sensitive to salt but gradually developed into a salt-insensitive interaction. Thus, the interaction requires a structural change in the interaction partner and leads to a conformational change in calreticulin itself. The implications of these results are that calreticulin may function as a general response modifier for a whole group of immunologically important proteins.

  1. Ligand-Induced Stability of Gold Nanoclusters: Thiolate versus Selenolate.

    Science.gov (United States)

    Kurashige, Wataru; Yamaguchi, Masaki; Nobusada, Katsuyuki; Negishi, Yuichi

    2012-09-20

    Thiolate-protected gold nanoclusters have attracted considerable attention as building blocks for new functional materials and have been extensively researched. Some studies have reported that changing the ligand of these gold nanoclusters from thiolate to selenolate increases cluster stability. To confirm this, in this study, we compare the stabilities of precisely synthesized [Au25(SC8H17)18](-) and [Au25(SeC8H17)18](-) against degradation in solution, thermal dissolution, and laser fragmentation. The results demonstrate that changing the ligand from thiolate to selenolate increases cluster stability in reactions involving dissociation of the gold-ligand bond but reduces cluster stability in reactions involving intramolecular dissociation of the ligand. These results reveal that using selenolate ligands makes it possible to produce gold clusters that are more stable against degradation in solution than thiolate-protected gold nanoclusters.

  2. Development of chiral sulfoxide ligands for asymmetric catalysis.

    Science.gov (United States)

    Trost, Barry M; Rao, Meera

    2015-04-20

    Nitrogen-, phosphorus-, and oxygen-based ligands with chiral backbones have been the historic workhorses of asymmetric transition-metal-catalyzed reactions. On the contrary, sulfoxides containing chirality at the sulfur atom have mainly been used as chiral auxiliaries for diastereoselective reactions. Despite several distinct advantages over traditional ligand scaffolds, such as the proximity of the chiral information to the metal center and the ability to switch between S and O coordination, these compounds have only recently emerged as a versatile class of chiral ligands. In this Review, we detail the history of the development of chiral sulfoxide ligands for asymmetric catalysis. We also provide brief descriptions of metal-sulfoxide bonding and strategies for the synthesis of enantiopure sulfoxides. Finally, insights into the future development of this underutilized ligand class are discussed.

  3. Polypharmacology: in silico methods of ligand design and development.

    Science.gov (United States)

    McKie, Samuel A

    2016-04-01

    How to design a ligand to bind multiple targets, rather than to a single target, is the focus of this review. Rational polypharmacology draws on knowledge that is both broad ranging and hierarchical. Computer-aided multitarget ligand design methods are described according to their nested knowledge level. Ligand-only and then receptor-ligand strategies are first described; followed by the metabolic network viewpoint. Subsequently strategies that view infectious diseases as multigenomic targets are discussed, and finally the disease level interpretation of medicinal therapy is considered. As yet there is no consensus on how best to proceed in designing a multitarget ligand. The current methodologies are bought together in an attempt to give a practical overview of how polypharmacology design might be best initiated.

  4. Predicting protein-ligand affinity with a random matrix framework.

    Science.gov (United States)

    Lee, Alpha A; Brenner, Michael P; Colwell, Lucy J

    2016-11-29

    Rapid determination of whether a candidate compound will bind to a particular target receptor remains a stumbling block in drug discovery. We use an approach inspired by random matrix theory to decompose the known ligand set of a target in terms of orthogonal "signals" of salient chemical features, and distinguish these from the much larger set of ligand chemical features that are not relevant for binding to that particular target receptor. After removing the noise caused by finite sampling, we show that the similarity of an unknown ligand to the remaining, cleaned chemical features is a robust predictor of ligand-target affinity, performing as well or better than any algorithm in the published literature. We interpret our algorithm as deriving a model for the binding energy between a target receptor and the set of known ligands, where the underlying binding energy model is related to the classic Ising model in statistical physics.

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

    Science.gov (United States)

    Hupp, Joseph T.; Mulfort, Karen L.; Snurr, Randall Q.; Bae, Youn-Sang

    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.

  6. 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

  7. Electronic spectra and photophysics of platinum(II) complexes with alpha-diimine ligands - Solid-state effects. I - Monomers and ligand pi dimers

    Science.gov (United States)

    Miskowski, Vincent M.; Houlding, Virginia H.

    1989-01-01

    Two types of emission behavior for Pt(II) complexes containing alpha-diimine ligands have been observed in dilute solution. If the complex also has weak field ligands such as chloride, ligand field (d-d) excited states become the lowest energy excited states. If only strong field ligands are present, a diimine 3(pi-pi/asterisk/) state becomes the lowest. In none of the cases studied did metal-to-ligand charge transfer excited state lie lowest.

  8. Identification of Soft Matter Binding Peptide Ligands Using Phage Display.

    Science.gov (United States)

    Günay, Kemal Arda; Klok, Harm-Anton

    2015-10-21

    Phage display is a powerful tool for the selection of highly affine, short peptide ligands. While originally primarily used for the identification of ligands to proteins, the scope of this technique has significantly expanded over the past two decades. Phage display nowadays is also increasingly applied to identify ligands that selectively bind with high affinity to a broad range of other substrates including natural and biological polymers as well as a variety of low-molecular-weight organic molecules. Such peptides are of interest for various reasons. The ability to selectively and with high affinity bind to the substrate of interest allows the conjugation or immobilization of, e.g., nanoparticles or biomolecules, or generally, facilitates interactions at materials interfaces. On the other hand, presentation of peptide ligands that selectively bind to low-molecular-weight organic materials is of interest for the development of sensor surfaces. The aim of this article is to highlight the opportunities provided by phage display for the identification of peptide ligands that bind to synthetic or natural polymer substrates or to small organic molecules. The article will first provide an overview of the different peptide ligands that have been identified by phage display that bind to these "soft matter" targets. The second part of the article will discuss the different characterization techniques that allow the determination of the affinity of the identified ligands to the respective substrates.

  9. Ligand-based identification of environmental estrogens

    Energy Technology Data Exchange (ETDEWEB)

    Waller, C.L. [Environmental Protection Agency, Research Triangle Park, NC (United States); Oprea, T.I. [Los Alamos National Lab., NM (United States); Chae, K. [National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States)] [and others

    1996-12-01

    Comparative molecular field analysis (CoMFA), a three-dimensional quantitative structure-activity relationship (3D-QSAR) paradigm, was used to examine the estrogen receptor (ER) binding affinities of a series of structurally diverse natural, synthetic, and environmental chemicals of interest. The CoMFA/3D-QSAR model is statistically robust and internally consistent, and successfully illustrates that the overall steric and electrostatic properties of structurally diverse ligands for the estrogen receptor are both necessary and sufficient to describe the binding affinity. The ability of the model to accurately predict the ER binding affinity of an external test set of molecules suggests that structure-based 3D-QSAR models may be used to supplement the process of endocrine disrupter identification through prioritization of novel compounds for bioassay. The general application of this 3D-QSAR model within a toxicological framework is, at present, limited only by the quantity and quality of biological data for relevant biomarkers of toxicity and hormonal responsiveness. 28 refs., 12 figs., 9 tabs.

  10. 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

  11. 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 neurotransmitter...... ligands in a one-pot reaction. The methodol. establishes a facile route towards bivalent neurotransmitter ligands, and libraries of in total 40 sym. and non-sym. bivalent and monovalent dopamine and serotonin compds. linked through alkyl or PEG spacers of varying length were prepd. Interestingly...

  12. Ligands recognizing the minor groove of DNA: development and applications.

    Science.gov (United States)

    Wemmer, D E

    Polyamide ligands comprised of pyrrole, imidazole and hydroxypyrrole rings have been developed over the past decade which can be used to target many different, predetermined DNA sequences through recognition of functional groups in the minor groove. The design principles for these ligands are described with a description of the characterization of their binding. Variations containing linked recognition modules have been described which allow high affinity and specificity recognition of DNA sequences of over 15 base pairs. Recent applications of these ligands in affecting biological response through competition with proteins for DNA binding sites are reviewed. Copyright 2001 John Wiley & Sons, Inc.

  13. Ligands targeting the excitatory amino acid transporters (EAATs).

    Science.gov (United States)

    Dunlop, John; Butera, John A

    2006-01-01

    This review provides an overview of ligands for the excitatory amino acid transporters (EAATs), a family of high-affinity glutamate transporters localized to the plasma membrane of neurons and astroglial cells. Ligand development from the perspective of identifying novel and more selective tools for elucidating transporter subtype function, and the potential of transporter ligands in a therapeutic setting are discussed. Acute pharmacological modulation of EAAT activity in the form of linear and conformationally restricted glutamate and aspartate analogs is presented, in addition to recent strategies aimed more toward modulating transporter expression levels, the latter of particular significance to the development of transporter based therapeutics.

  14. Role of ligand-dependent GR phosphorylation and half-life in determination of ligand-specific transcriptional activity.

    Science.gov (United States)

    Avenant, Chanel; Ronacher, Katharina; Stubsrud, Elisabeth; Louw, Ann; Hapgood, Janet P

    2010-10-07

    A central question in glucocorticoid mechanism of action via the glucocorticoid receptor (GR) is what determines ligand-selective transcriptional responses. Using a panel of 12 GR ligands, we show that the extent of GR phosphorylation at S226 and S211, GR half-life and transcriptional response, occur in a ligand-selective manner. While GR phosphorylation at S226 was shown to inhibit maximal transcription efficacy, phosphorylation at S211 is required for maximal transactivation, but not for transrepression efficacy. Both ligand-selective GR phosphorylation and half-life correlated with efficacy for transactivation and transrepression. For both expressed and endogenous GR, in two different cell lines, agonists resulted in the greatest extent of phosphorylation and the greatest extent of GR downregulation, suggesting a link between these functions. However, using phosphorylation-deficient GR mutants we established that phosphorylation of the GR at S226 or S211 does not determine the rank order of ligand-selective GR transactivation. These results are consistent with a model whereby ligand-selective GR phosphorylation and half-life are a consequence of upstream events, such as ligand-specific GR conformations, which are maintained in the phosphorylation mutants.

  15. Ligand-biased ensemble receptor docking (LigBEnD): a hybrid ligand/receptor structure-based approach

    Science.gov (United States)

    Lam, Polo C.-H.; Abagyan, Ruben; Totrov, Maxim

    2017-09-01

    Ligand docking to flexible protein molecules can be efficiently carried out through ensemble docking to multiple protein conformations, either from experimental X-ray structures or from in silico simulations. The success of ensemble docking often requires the careful selection of complementary protein conformations, through docking and scoring of known co-crystallized ligands. False positives, in which a ligand in a wrong pose achieves a better docking score than that of native pose, arise as additional protein conformations are added. In the current study, we developed a new ligand-biased ensemble receptor docking method and composite scoring function which combine the use of ligand-based atomic property field (APF) method with receptor structure-based docking. This method helps us to correctly dock 30 out of 36 ligands presented by the D3R docking challenge. For the six mis-docked ligands, the cognate receptor structures prove to be too different from the 40 available experimental Pocketome conformations used for docking and could be identified only by receptor sampling beyond experimentally explored conformational subspace.

  16. The Foundations of Protein-Ligand Interaction

    Science.gov (United States)

    Klebe, Gerhard

    For the specific design of a drug we must first answer the question: How does a drug achieve its activity? An active ingredient must, in order to develop its action, bind to a particular target molecule in the body. Usually this is a protein, but also nucleic acids in the form of RNA and DNA can be target structures for active agents. The most important condition for binding is at first that the active agent exhibits the correct size and shape in order to optimally fit into a cavity exposed to the surface of the protein, the "bindingpocket". It is further necessary for the surface properties of the ligand and protein to be mutually compatible to form specific interactions. In 1894 Emil Fischer compared the exact fit of a substrate for the catalytic centre of an enzyme with the picture of a "lock-and-key". Paul Ehrlich coined in 1913 "Corpora non agunt nisi fixata", literally "bodies do not work when they are not bound". He wanted to imply that active agents that are meant to kill bacteria or parasites must be "fixed" by them, i.e. linked to their structures. Both concepts form the starting point for any rational concept in the development of active pharmaceutical ingredients. In many respects they still apply today. A drug must, after being administered, reach its target and interact with a biological macromolecule. Specific agents have a large affinity and sufficient selectivity to bind to the macromolecule's active site. This is the only way they can develop the desired biological activity without side-effects.

  17. Enantioselective catalysis with tropos ligands in chiral ionic liquids.

    Science.gov (United States)

    Schmitkamp, Mike; Chen, Dianjun; Leitner, Walter; Klankermayer, Jürgen; Franciò, Giancarlo

    2007-10-21

    Enantioselective homogeneous rhodium-catalysed hydrogenation using tropoisomeric biphenylphosphine ligands was accomplished in readily available chiral ionic liquids and the catalytic system could be reused after extraction with scCO(2).

  18. Synthesis and Catalytic Activity of Two New Cyclic Tetraaza Ligands

    Directory of Open Access Journals (Sweden)

    Burkhard König

    2003-05-01

    Full Text Available Two new chiral cyclic tetraaza ligands were synthesized and characterized. Their catalytic activity was tested in the asymmetric addition of diethylzinc to benzaldehyde. The expected secondary alcohol was obtained in moderate yields, but with very low enantioselectivity.

  19. Ligand Binding to Macromolecules: Allosteric and Sequential Models of Cooperativity.

    Science.gov (United States)

    Hess, V. L.; Szabo, Attila

    1979-01-01

    A simple model is described for the binding of ligands to macromolecules. The model is applied to the cooperative binding by hemoglobin and aspartate transcarbamylase. The sequential and allosteric models of cooperative binding are considered. (BB)

  20. Observations on the ligand selectivity of the melanocortin 2 receptor.

    Science.gov (United States)

    Veo, Kristopher; Reinick, Christina; Liang, Liang; Moser, Emily; Angleson, Joseph K; Dores, Robert M

    2011-05-15

    The melanocortin 2 receptor (MC2R) is unique in terms of ligand selectivity and in vitro expression in mammalian cell lines as compared to the other four mammalian MCRs. It is well established that ACTH is the only melanocortin ligand that can activate the ACTH receptor (i.e., melanocortin 2 receptor). Recent studies have provided new insights into the presence of a common binding site for the HFRW motif common to all melanocortin ligands. However, the activation of the melanocortin 2 receptor requires an additional amino acid motif that is only found in the sequence of ACTH. This mini-review will focus on these two topics and provide a phylogenetic perspective on the evolution of MC2R ligand selectivity.

  1. 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.

  2. Fluorescent ligand for human progesterone receptor imaging in live cells.

    Science.gov (United States)

    Weinstain, Roy; Kanter, Joan; Friedman, Beth; Ellies, Lesley G; Baker, Michael E; Tsien, Roger Y

    2013-05-15

    We employed molecular modeling to design and then synthesize fluorescent ligands for the human progesterone receptor. Boron dipyrromethene (BODIPY) or tetramethylrhodamine were conjugated to the progesterone receptor antagonist RU486 (Mifepristone) through an extended hydrophilic linker. The fluorescent ligands demonstrated comparable bioactivity to the parent antagonist in live cells and triggered nuclear translocation of the receptor in a specific manner. The BODIPY labeled ligand was applied to investigate the dependency of progesterone receptor nuclear translocation on partner proteins and to show that functional heat shock protein 90 but not immunophilin FKBP52 activity is essential. A tissue distribution study indicated that the fluorescent ligand preferentially accumulates in tissues that express high levels of the receptor in vivo. The design and properties of the BODIPY-labeled RU486 make it a potential candidate for in vivo imaging of PR by positron emission tomography through incorporation of (18)F into the BODIPY core.

  3. Specific activity of radioiodine-labelled human chorionic gonadotropin ligand

    Energy Technology Data Exchange (ETDEWEB)

    Crespi, M. (South African Inst. for Medical Research, Sandringham. National Inst. for Virology); Kay, G.W.; Van der Walt, L.A. (South African Inst. for Medical Research, Johannesburg. Dept. of Pathology)

    1983-10-01

    The article deals with the determination of the specific activity of radioiodine-labelled human chorionic gonadotropin ligand. The iodiation of human chorionic gonadotropin and the counting efficiency of /sup 125/I are discussed.

  4. Steered molecular dynamics simulations of protein-ligand interactions

    Institute of Scientific and Technical Information of China (English)

    XU; Yechun; SHEN; Jianhua; LUO; Xiaomin; SHEN; Xu; CHEN; Ka

    2004-01-01

    Studies of protein-ligand interactions are helpful to elucidating the mechanisms of ligands, providing clues for rational drug design. The currently developed steered molecular dynamics (SMD) is a complementary approach to experimental techniques in investigating the biochemical processes occurring at microsecond or second time scale, thus SMD may provide dynamical and kinetic processes of ligand-receptor binding and unbinding, which cannot be accessed by the experimental methods. In this article, the methodology of SMD is described, and the applications of SMD simulations for obtaining dynamic insights into protein-ligand interactions are illustrated through two of our own examples. One is associated with the simulations of binding and unbinding processes between huperzine A and acetylcholinesterase, and the other is concerned with the unbinding process of α-APA from HIV-1 reverse transcriptase.

  5. CD40 ligand immunotherapy in cancer: an efficient approach.

    Science.gov (United States)

    Kuwashima, N; Kageyama, S; Eto, Y; Urashima, M

    2001-01-01

    Cancer cells do not elicit a clinically sufficient anti-tumor immune response that results in tumor rejection. Recently, many investigators have been trying to enhance anti-tumor immunity and encouraging results have been reported. This review will discuss current anti-cancer immunotherapy; interleukin-2 therapy, tumor vaccine secreting Granulocyte macrophage-colony stimulating factor, dendritic cells fused with tumor cells, and CD40 ligand immunotherapy. Moreover, we introduce our two kinds of CD40 ligand immuno-genetherapy; (1) oral CD40 ligand gene therapy against lymphoma using attenuated Salmonella typhimurium (published in BLOOD 2000), (2) cancer vaccine transfected with CD40 ligand ex vivo for neuroblastoma (unpublished). Both approaches resulted in a high degree of protection against the tumor progression and they are simple and safe in the murine system.

  6. 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.

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

    Science.gov (United States)

    Veenman, Leo; Vainshtein, Alex; Yasin, Nasra; Azrad, Maya; Gavish, Moshe

    2016-01-01

    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.

  8. 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 ......-aggregated IgG, indicating that the ligand could be used both as a primary purification step of IgG as well as a subsequent polishing step. (C) 2012 Elsevier B.V. All rights reserved....

  9. Predicting protein-ligand affinity with a random matrix framework

    OpenAIRE

    Lee, Alpha Albert; Brenner, MP; Colwell, Lucy Jane

    2016-01-01

    Rapid determination of whether a candidate compound will bind to a particular target receptor remains a stumbling block in drug discovery. We use an approach inspired by random matrix theory to decompose the known ligand set of a target in terms of orthogonal "signals" of salient chemical features, and distinguish these from the much larger set of ligand chemical features that are not relevant for binding to that particular target receptor. After removing the noise caused by finite sampling, ...

  10. 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.

  11. Tailoring the Properties of Metallic Clusters by Ligand Coatings

    OpenAIRE

    Fresch, Barbara

    2014-01-01

    Tuning the properties of metallic clusters using different protecting ligand shells is an important step toward the application-orientated design of nanoparticles for nano-electronics and catalysis. An attractive property of these materials is the ability to engineer ligand shells composed of different molecules that influence the electronic structure of the system due to their chemical interaction with the metal core. Sometimes properties are not simply additive, and cooperative effects emer...

  12. Dynamic 3D cell culture via a chemoselective photoactuated ligand.

    Science.gov (United States)

    Westcott, Nathan P; Luo, Wei; Goldstein, Jeffrey; Yousaf, Muhammad N

    2014-09-01

    A new strategy to create a dynamic scaffold for three-dimensional (3D) cell experiments based on a photo-activated cell adhesive peptide ligand is described. After polymerization, the inert matrix becomes cell adhesive by chemoselective modification through the conjugation of oxyamine-terminated ligands. Furthermore, spatial and temporal control of cell culture within the 3D matrix was achieved by the use of a biospecific photoprotected peptide and visualized by confocal microscopy.

  13. Structural Basis of Cooperative Ligand Binding by the Glycine Riboswitch

    OpenAIRE

    Butler, Ethan B.; Xiong, Yong; Wang, Jimin; Strobel, Scott A.

    2011-01-01

    The glycine riboswitch regulates gene expression through the cooperative recognition of its amino acid ligand by a tandem pair of aptamers. A 3.6Å crystal structure of the tandem riboswitch from the glycine permease operon of Fusobacterium nucleatum reveals the glycine binding sites and an extensive network of interactions, largely mediated by asymmetric A-minor contacts, that serve to communicate ligand binding status between the aptamers. These interactions provide a structural basis for ho...

  14. Increased CD40 ligand in patients with acute anterior uveitis

    DEFF Research Database (Denmark)

    Øgard, Carsten; Sørensen, Torben Lykke; Krogh, Erik

    2005-01-01

    The inflammatory response in acute anterior uveitis (AU) is believed to be primarily mediated by autoreactive T-cells. We wanted to evaluate whether the T-cell activation marker CD40 ligand is involved in the AU immunopathogenesis.......The inflammatory response in acute anterior uveitis (AU) is believed to be primarily mediated by autoreactive T-cells. We wanted to evaluate whether the T-cell activation marker CD40 ligand is involved in the AU immunopathogenesis....

  15. Delivering carbide ligands to sulfide-rich clusters.

    Science.gov (United States)

    Reinholdt, Anders; Herbst, Konrad; Bendix, Jesper

    2016-02-01

    The propensity of the terminal ruthenium carbide Ru(C)Cl2(PCy3)2 (RuC) to form carbide bridges to electron-rich transition metals enables synthetic routes to metal clusters with coexisting carbide and sulfide ligands. Electrochemical experiments show the Ru≡C ligand to exert a relatively large electron-withdrawing effect compared with PPh3, effectively shifting redox potentials.

  16. Agonists and Antagonists of TGF-β Family Ligands.

    Science.gov (United States)

    Chang, Chenbei

    2016-08-01

    The discovery of the transforming growth factor β (TGF-β) family ligands and the realization that their bioactivities need to be tightly controlled temporally and spatially led to intensive research that has identified a multitude of extracellular modulators of TGF-β family ligands, uncovered their functions in developmental and pathophysiological processes, defined the mechanisms of their activities, and explored potential modulator-based therapeutic applications in treating human diseases. These studies revealed a diverse repertoire of extracellular and membrane-associated molecules that are capable of modulating TGF-β family signals via control of ligand availability, processing, ligand-receptor interaction, and receptor activation. These molecules include not only soluble ligand-binding proteins that were conventionally considered as agonists and antagonists of TGF-β family of growth factors, but also extracellular matrix (ECM) proteins and proteoglycans that can serve as "sink" and control storage and release of both the TGF-β family ligands and their regulators. This extensive network of soluble and ECM modulators helps to ensure dynamic and cell-specific control of TGF-β family signals. This article reviews our knowledge of extracellular modulation of TGF-β growth factors by diverse proteins and their molecular mechanisms to regulate TGF-β family signaling.

  17. 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.

  18. Phage Selection of Chemically Stabilized α-Helical Peptide Ligands.

    Science.gov (United States)

    Diderich, Philippe; Bertoldo, Davide; Dessen, Pierre; Khan, Maola M; Pizzitola, Irene; Held, Werner; Huelsken, Joerg; Heinis, Christian

    2016-05-20

    Short α-helical peptides stabilized by linkages between constituent amino acids offer an attractive format for ligand development. In recent years, a range of excellent ligands based on stabilized α-helices were generated by rational design using α-helical peptides of natural proteins as templates. Herein, we developed a method to engineer chemically stabilized α-helical ligands in a combinatorial fashion. In brief, peptides containing cysteines in position i and i + 4 are genetically encoded by phage display, the cysteines are modified with chemical bridges to impose α-helical conformations, and binders are isolated by affinity selection. We applied the strategy to affinity mature an α-helical peptide binding β-catenin. We succeeded in developing ligands with Kd's as low as 5.2 nM, having >200-fold improved affinity. The strategy is generally applicable for affinity maturation of any α-helical peptide. Compared to hydrocarbon stapled peptides, the herein evolved thioether-bridged peptide ligands can be synthesized more easily, as no unnatural amino acids are required and the cyclization reaction is more efficient and yields no stereoisomers. A further advantage of the thioether-bridged peptide ligands is that they can be expressed recombinantly as fusion proteins.

  19. Orphan receptor ligand discovery by pickpocketing pharmacological neighbors.

    Science.gov (United States)

    Ngo, Tony; Ilatovskiy, Andrey V; Stewart, Alastair G; Coleman, James L J; McRobb, Fiona M; Riek, R Peter; Graham, Robert M; Abagyan, Ruben; Kufareva, Irina; Smith, Nicola J

    2017-02-01

    Understanding the pharmacological similarity of G protein-coupled receptors (GPCRs) is paramount for predicting ligand off-target effects, drug repurposing, and ligand discovery for orphan receptors. Phylogenetic relationships do not always correctly capture pharmacological similarity. Previous family-wide attempts to define pharmacological relationships were based on three-dimensional structures and/or known receptor-ligand pairings, both unavailable for orphan GPCRs. Here, we present GPCR-CoINPocket, a novel contact-informed neighboring pocket metric of GPCR binding-site similarity that is informed by patterns of ligand-residue interactions observed in crystallographically characterized GPCRs. GPCR-CoINPocket is applicable to receptors with unknown structure or ligands and accurately captures known pharmacological relationships between GPCRs, even those undetected by phylogeny. When applied to orphan receptor GPR37L1, GPCR-CoINPocket identified its pharmacological neighbors, and transfer of their pharmacology aided in discovery of the first surrogate ligands for this orphan with a 30% success rate. Although primarily designed for GPCRs, the method is easily transferable to other protein families.

  20. Riboswitch structure in the ligand-free state.

    Science.gov (United States)

    Liberman, Joseph A; Wedekind, Joseph E

    2012-01-01

    Molecular investigations of riboswitches bound to small-molecule effectors have produced a wealth of information on how these molecules achieve high affinity and specificity for a target ligand. X-ray crystal structures have been determined for the ligand-free state for representatives of the preQ₁-I, S-adenosylmethionine I, lysine, and glycine aptamer classes. These structures in conjunction with complimentary techniques, such as in-line probing, NMR spectroscopy, Förster resonance energy transfer, small-angle scattering, and computational simulations, have demonstrated that riboswitches adopt multiple conformations in the absence of ligand. Despite a number of investigations that support ligand-dependent folding, mounting evidence suggests that free-state riboswitches interact with their effectors in the sub-populations of largely prefolded states as embodied by the principle of conformational selection, which has been documented extensively for protein-mediated ligand interactions. Fundamental riboswitch investigations of the bound and free states have advanced our understanding of RNA folding, ligand recognition, and how these factors culminate in communication between an aptamer and its expression platform. An understanding of these topics is essential to comprehend riboswitch gene regulation at the molecular level, which has already provided a basis to understand the mechanism of action of natural antimicrobials.

  1. Ligand exchange in quaternary alloyed nanocrystals--a spectroscopic study.

    Science.gov (United States)

    Gabka, Grzegorz; Bujak, Piotr; Giedyk, Kamila; Kotwica, Kamil; Ostrowski, Andrzej; Malinowska, Karolina; Lisowski, Wojciech; Sobczak, Janusz W; Pron, Adam

    2014-11-14

    Exchange of initial, predominantly stearate ligands for pyridine in the first step and butylamine (BA) or 11-mercaptoundecanoic acid (MUA) in the second one was studied for alloyed quaternary Cu-In-Zn-S nanocrystals. The NMR results enabled us to demonstrate, for the first time, direct binding of the pyridine labile ligand to the nanocrystal surface as evidenced by paramagnetic shifts of the three signals attributed to its protons to 7.58, 7.95 and 8.75 ppm. XPS investigations indicated, in turn, a significant change in the composition of the nanocrystal surface upon the exchange of initial ligands for pyridine, which being enriched in indium in the 'as prepared' form became enriched in zinc after pyridine binding. This finding indicated that the first step of ligand exchange had to involve the removal of the surface layer enriched in indium with simultaneous exposure of a new, zinc-enriched layer. In the second ligand exchange step (replacement of pyridine with BA or MUA) the changes in the nanocrystal surface compositions were much less significant. The presence of zinc in the nanocrystal surface layer turned out necessary for effective binding of pyridine as shown by a comparative study of ligand exchange in Cu-In-Zn-S, Ag-In-Zn-S and CuInS2, carried out by complementary XPS and NMR investigations.

  2. Solution NMR Structure of a Ligand/Hybrid-2-G-Quadruplex Complex Reveals Rearrangements that Affect Ligand Binding.

    Science.gov (United States)

    Wirmer-Bartoschek, Julia; Bendel, Lars Erik; Jonker, Hendrik R A; Grün, J Tassilo; Papi, Francesco; Bazzicalupi, Carla; Messori, Luigi; Gratteri, Paola; Schwalbe, Harald

    2017-06-12

    Telomeric G-quadruplexes have recently emerged as drug targets in cancer research. Herein, we present the first NMR structure of a telomeric DNA G-quadruplex that adopts the biologically relevant hybrid-2 conformation in a ligand-bound state. We solved the complex with a metalorganic gold(III) ligand that stabilizes G-quadruplexes. Analysis of the free and bound structures reveals structural changes in the capping region of the G-quadruplex. The ligand is sandwiched between one terminal G-tetrad and a flanking nucleotide. This complex structure involves a major structural rearrangement compared to the free G-quadruplex structure as observed for other G-quadruplexes in different conformations, invalidating simple docking approaches to ligand-G-quadruplex structure determination. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. 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.

  4. Integration of screening and identifying ligand(s) from medicinal plant extracts based on target recognition by using NMR spectroscopy

    OpenAIRE

    2015-01-01

    Authors: Yalin Tang, Qian Shang, Junfeng Xiang, Qianfan Yang, Qiuju Zhou, Lin Li, Hong Zhang, Qian Li, Hongxia Sun, Aijiao Guan, Wei Jiang & Wei Gai ### Abstract This protocol presents the screening of ligand(s) from medicinal plant extracts based on target recognition by using NMR spectroscopy. A detailed description of sample preparation and analysis process is provided. NMR spectroscopies described here are 1H NMR, diffusion-ordered spectroscopy (DOSY), relaxation-edited NMR, ...

  5. electronic Ligand Builder and Optimisation Workbench (eLBOW): A tool for ligand coordinate and restraint generation

    Energy Technology Data Exchange (ETDEWEB)

    Moriarty, Nigel; Grosse-Kunstleve, Ralf; Adams, Paul

    2009-07-01

    The electronic Ligand Builder and Optimisation Workbench (eLBOW) is a program module of the PHENIX suite of computational crystallographic software. It's designed to be a flexible procedure using simple and fast quantum chemical techniques to provide chemically accurate information for novel and known ligands alike. A variety of input formats and options allow for the attainment of a number of diverse goals including geometry optimisation and generation of restraints.

  6. 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.

  7. Non-peptide ligand binding to the formyl peptide receptor FPR2--A comparison to peptide ligand binding modes.

    Science.gov (United States)

    Stepniewski, Tomasz M; Filipek, Slawomir

    2015-07-15

    Ligands of the FPR2 receptor initiate many signaling pathways including activation of phospholipase C, protein kinase C, the mitogen-activated protein kinase, and phosphatidylinositol 3-kinase/protein kinase B pathway. The possible actions include also calcium flux, superoxide generation, as well as migration and proliferation of monocytes. FPR2 activation may induce a pro- and anti-inflammatory effect depending on the ligand type. It is also found that this receptor is involved in tumor growth. Most of currently known FPR2 ligands are agonists since they were designed based on N-formyl peptides, which are natural agonists of formyl receptors. Since the non-peptide drugs are indispensable for effective treatment strategies, we performed a docking study of such ligands employing a generated dual template homology model of the FPR2 receptor. The study revealed different binding modes of particular classes of these drugs. Based on the obtained docking poses we proposed a detailed location of three hydrophobic pockets in orthosteric binding site of FPR2. Our model emphasizes the importance of aromatic stacking, especially with regard to residues His102(3.29) and Phe257(6.51), for binding of FPR2 ligands. We also identified other residues important for non-peptide ligand binding in the binding site of FPR2. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Ligand-based virtual screening under partial shape constraints

    Science.gov (United States)

    von Behren, Mathias M.; Rarey, Matthias

    2017-03-01

    Ligand-based virtual screening has proven to be a viable technology during the search for new lead structures in drug discovery. Despite the rapidly increasing number of published methods, meaningful shape matching as well as ligand and target flexibility still remain open challenges. In this work, we analyze the influence of knowledge-based sterical constraints on the performance of the recently published ligand-based virtual screening method mRAISE. We introduce the concept of partial shape matching enabling a more differentiated view on chemical structure. The new method is integrated into the LBVS tool mRAISE providing multiple options for such constraints. The applied constraints can either be derived automatically from a protein-ligand complex structure or by manual selection of ligand atoms. In this way, the descriptor directly encodes the fit of a ligand into the binding site. Furthermore, the conservation of close contacts between the binding site surface and the query ligand can be enforced. We validated our new method on the DUD and DUD-E datasets. Although the statistical performance remains on the same level, detailed analysis reveal that for certain and especially very flexible targets a significant improvement can be achieved. This is further highlighted looking at the quality of calculated molecular alignments using the recently introduced mRAISE dataset. The new partial shape constraints improved the overall quality of molecular alignments especially for difficult targets with highly flexible or different sized molecules. The software tool mRAISE is freely available on Linux operating systems for evaluation purposes and academic use (see http://www.zbh.uni-hamburg.de/raise).

  9. Synthesis and enzymatic cleavage of dual-ligand quantum dots

    Energy Technology Data Exchange (ETDEWEB)

    Sewell, Sarah L. [Department of Biomedical Engineering, Vanderbilt University, Nashville, TN (United States); Giorgio, Todd D., E-mail: todd.d.giorgio@vanderbilt.edu [Department of Biomedical Engineering, Vanderbilt University, Nashville, TN (United States); Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN (United States)

    2009-05-05

    Site directed therapy promises to minimize treatment-limiting systemic effects associated with cytotoxic agents that have no specificity for pathologic tissues. One general strategy is to target cell surface receptors uniquely presented on particular tissues. Highly specific in vivo targeting of an emerging neoplasm through a single molecular recognition mechanism has not generally been successful. Nonspecific binding and specific binding to non-target cells compromise the therapeutic index of small molecule, ubiquitous cancer targeting ligands. In this work, we have designed and fabricated a nanoparticle (NP) construct that could potentially overcome the current limitations of targeted in vivo delivery. Quantum dots (QDs) were functionalized with a poly(ethylene glycol) (PEG) modified to enable specific cleavage by matrix metalloprotease-7 (MMP-7). The QDs were further functionalized with folic acid, a ligand for a cell surface receptor that is overexpressed in many tumors, but also expressed in some normal tissues. The nanomolecular construct is designed so that the PEG initially conceals the folate ligand and construct binding to cells is inhibited. MMP-7 activated peptide cleavage and subsequent unmasking of the folate ligand occurs only near tumor tissue, resulting in a proximity activated (PA) targeting system. QDs functionalized with both the MMP-7 cleavable substrate and folic acid were successfully synthesized and characterized. The proteolytic capability of the dual ligand QD construct was quantitatively assessed by fluorometric analysis and compared to a QD construct functionalized with only the PA ligand. The dual ligand PA nanoparticles studied here exhibit significant susceptibility to cleavage by MMP-7 at physiologically relevant conditions. The capacity to autonomously convert a biopassivated nanostructure to a tissue-specific targeted delivery agent in vivo represents a paradigm change for site-directed therapies.

  10. Ligand-based virtual screening under partial shape constraints

    Science.gov (United States)

    von Behren, Mathias M.; Rarey, Matthias

    2017-04-01

    Ligand-based virtual screening has proven to be a viable technology during the search for new lead structures in drug discovery. Despite the rapidly increasing number of published methods, meaningful shape matching as well as ligand and target flexibility still remain open challenges. In this work, we analyze the influence of knowledge-based sterical constraints on the performance of the recently published ligand-based virtual screening method mRAISE. We introduce the concept of partial shape matching enabling a more differentiated view on chemical structure. The new method is integrated into the LBVS tool mRAISE providing multiple options for such constraints. The applied constraints can either be derived automatically from a protein-ligand complex structure or by manual selection of ligand atoms. In this way, the descriptor directly encodes the fit of a ligand into the binding site. Furthermore, the conservation of close contacts between the binding site surface and the query ligand can be enforced. We validated our new method on the DUD and DUD-E datasets. Although the statistical performance remains on the same level, detailed analysis reveal that for certain and especially very flexible targets a significant improvement can be achieved. This is further highlighted looking at the quality of calculated molecular alignments using the recently introduced mRAISE dataset. The new partial shape constraints improved the overall quality of molecular alignments especially for difficult targets with highly flexible or different sized molecules. The software tool mRAISE is freely available on Linux operating systems for evaluation purposes and academic use (see http://www.zbh.uni-hamburg.de/raise).

  11. Ligand and Metalloligand Design for Macrocycles, Multimetallic Arrays, Coordination Polymers and Assemblies

    OpenAIRE

    E. C. Constable; Housecroft, C. E.

    2016-01-01

    This overview of ligand design focuses on three areas: (i) principles of ligand binding, the formation of complexes, and popular strategies for ligand synthesis; (ii) ligand design in macrocyclic complexes, coordination polymers and networks and metallopolygons, and assembly strategies based upon the use of metalloligand building blocks; (iii) ligand design for the extraction and transport of metals. This area of coordination chemistry is too large to permit a comprehensive survey in the spac...

  12. Aluminum complexes of the redox-active [ONO] pincer ligand.

    Science.gov (United States)

    Szigethy, Géza; Heyduk, Alan F

    2012-07-14

    A series of aluminum complexes containing the tridentate, redox-active ligand bis(3,5-di-tert-butyl-2-phenol)amine ([ONO]H(3)) in three different oxidation states were synthesized. The aluminum halide salts AlCl(3) and AlBr(3) were reacted with the doubly deprotonated form of the ligand to afford five-coordinate [ONHO(cat)]AlX(solv) complexes (1a, X = Cl, solv = OEt(2); 1b, X = Br, solv = THF), each having a trigonal bipyramidal coordination geometry at the aluminum and containing the [ONHO(cat)](2-) ligand with a protonated, sp(3)-hybridized nitrogen donor. The [ONO] ligand platform may also be added to aluminum through the use of the oxidized ligand salt [ONO(q)]K, which was reacted with AlCl(3) in the presence of either diphenylacetylacetonate (acacPh(2)(-)) or 8-oxyquinoline (quinO(-)) to afford [ONO(q)]Al(acacPh(2))Cl (2) or [ONO(q)]Al(quinO)Cl (3), respectively, with well-defined [ONO(q)](-) ligands. Quinonate complexes 2 and 3 were reduced by one electron to afford the corresponding complexes K{[ONO(sq)]Al(acacPh(2))(py)} (4) and K{[ONO(sq)]Al(quinO)(py)} (5), respectively, containing well-defined [ONO(sq)](2-) ligands. The addition of tetrachloro-1,2-quinone to 1a in the presence of pyridine resulted in the expulsion of HCl and the formation of an aluminum complex with two different redox active ligands, [ONO]Al(o-O(2)C(6)Cl(4))(py) (6). Similar results were obtained when 1a was reacted with 9,10-phenanthrenequinone to afford [ONO]Al(o-O(2)C(14)H(8))(py) (7) or with pyrene-4,5-dione to afford [ONO]Al(o-O(2)C(16)H(8))(py) (8). Structural, spectroscopic and preliminary magnetic measurements on 6-8 suggest ligand non-innocent redox behavior in these complexes.

  13. Coarse-grained molecular dynamics simulations of protein-ligand binding.

    Science.gov (United States)

    Negami, Tatsuki; Shimizu, Kentaro; Terada, Tohru

    2014-09-30

    Coarse-grained molecular dynamics (CGMD) simulations with the MARTINI force field were performed to reproduce the protein-ligand binding processes. We chose two protein-ligand systems, the levansucrase-sugar (glucose or sucrose), and LinB-1,2-dichloroethane systems, as target systems that differ in terms of the size and shape of the ligand-binding pocket and the physicochemical properties of the pocket and the ligand. Spatial distributions of the Coarse-grained (CG) ligand molecules revealed potential ligand-binding sites on the protein surfaces other than the real ligand-binding sites. The ligands bound most strongly to the real ligand-binding sites. The binding and unbinding rate constants obtained from the CGMD simulation of the levansucrase-sucrose system were approximately 10 times greater than the experimental values; this is mainly due to faster diffusion of the CG ligand in the CG water model. We could obtain dissociation constants close to the experimental values for both systems. Analysis of the ligand fluxes demonstrated that the CG ligand molecules entered the ligand-binding pockets through specific pathways. The ligands tended to move through grooves on the protein surface. Thus, the CGMD simulations produced reasonable results for the two different systems overall and are useful for studying the protein-ligand binding processes.

  14. Consensus virtual screening approaches to predict protein ligands.

    Science.gov (United States)

    Kukol, Andreas

    2011-09-01

    In order to exploit the advantages of receptor-based virtual screening, namely time/cost saving and specificity, it is important to rely on algorithms that predict a high number of active ligands at the top ranks of a small molecule database. Towards that goal consensus methods combining the results of several docking algorithms were developed and compared against the individual algorithms. Furthermore, a recently proposed rescoring method based on drug efficiency indices was evaluated. Among AutoDock Vina 1.0, AutoDock 4.2 and GemDock, AutoDock Vina was the best performing single method in predicting high affinity ligands from a database of known ligands and decoys. The rescoring of predicted binding energies with the water/octanol partition coefficient did not lead to an improvement averaged over ten receptor targets. Various consensus algorithms were investigated and a simple combination of AutoDock and AutoDock Vina results gave the most consistent performance that showed early enrichment of known ligands for all receptor targets investigated. In case a number of ligands is known for a specific target, every method proposed in this study should be evaluated. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  15. Kinetics of Receptor-Ligand Interactions in Immune Responses

    Institute of Scientific and Technical Information of China (English)

    Mian Long; Shouqin Lü; Ganyun Sun

    2006-01-01

    Receptor-ligand interactions in blood flow are crucial to initiate the biological processes as inflammatory cascade,platelet thrombosis, as well as tumor metastasis. To mediate cell adhesions, the interacting receptors and ligands must be anchored onto two apposing surfaces of two cells or a cell and a substratum, i.e., the two-dimensional (2D) binding, which is different from the binding of a soluble ligand in fluid phase to a receptor, i.e., three-dimensional (3D) binding. While numerous works have been focused on 3D kinetics of receptor-ligand interactions in immune systems, 2D kinetics and its regulations have less been understood, since no theoretical framework and experimental assays have been established until 1993. Not only does the molecular structure dominate 2D binding kinetics, but the shear force in blood flow also regulates cell adhesions mediated by interacting receptors and ligands. Here we provided the overview of current progresses in 2D bindings and regulations. Relevant issues of theoretical frameworks, experimental measurements, kinetic rates and binding affinities, and force regulations,were discussed.

  16. 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.

  17. A modified fluorescent intercalator displacement assay for RNA ligand discovery.

    Science.gov (United States)

    Asare-Okai, Papa Nii; Chow, Christine S

    2011-01-15

    Fluorescent intercalator displacement (FID) is a convenient and practical tool for identifying new nucleic acid-binding ligands. The success of FID is based on the fact that it can be fashioned into a versatile screening assay for assessing the relative binding affinities of compounds to nucleic acids. FID is a tagless approach; the target RNAs and the ligands or small molecules under investigation do not need to be modified in order to be examined. In this study, a modified FID assay for screening RNA-binding ligands was established using 3-methyl-2-((1-(3-(trimethylammonio)propyl)-4-quinolinylidene)methyl)benzothiazolium (TO-PRO) as the fluorescent indicator. Electrospray ionization mass spectrometry (ESI-MS) results provide direct evidence that correlates the reduction in fluorescence intensity observed in the FID assay with displacement of the dye molecule from RNA. The assay was successfully applied to screen a variety of RNA-binding ligands with a set of small hairpin RNAs. Ligands that bind with moderate affinity to the chosen RNA constructs (A-site, TAR [transactivation response element], h31 [helix 31], and H69 [helix 69] were identified. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Mapping of ligand-binding cavities in proteins.

    Science.gov (United States)

    Andersson, C David; Chen, Brian Y; Linusson, Anna

    2010-05-01

    The complex interactions between proteins and small organic molecules (ligands) are intensively studied because they play key roles in biological processes and drug activities. Here, we present a novel approach to characterize and map the ligand-binding cavities of proteins without direct geometric comparison of structures, based on Principal Component Analysis of cavity properties (related mainly to size, polarity, and charge). This approach can provide valuable information on the similarities and dissimilarities, of binding cavities due to mutations, between-species differences and flexibility upon ligand-binding. The presented results show that information on ligand-binding cavity variations can complement information on protein similarity obtained from sequence comparisons. The predictive aspect of the method is exemplified by successful predictions of serine proteases that were not included in the model construction. The presented strategy to compare ligand-binding cavities of related and unrelated proteins has many potential applications within protein and medicinal chemistry, for example in the characterization and mapping of "orphan structures", selection of protein structures for docking studies in structure-based design, and identification of proteins for selectivity screens in drug design programs.

  19. Protein-Ligand Docking Based on Beta-Shape

    Science.gov (United States)

    Kim, Chong-Min; Won, Chung-In; Kim, Jae-Kwan; Ryu, Joonghyun; Bhak, Jong; Kim, Deok-Soo

    Protein-ligand docking is to predict the location and orientation of a ligand with respect to a protein within its binding site, and has been known to be essential for the development of new drugs. The protein-ligand docking problem is usually formulated as an energy minimization problem to identify the docked conformation of the ligand. A ligand usually docks around a depressed region, called a pocket, on the surface of a protein. Presented in this paper is a docking method, called BetaDock, based on the newly developed geometric construct called the β-shape and the β-complex. To cope with the computational intractability, the global minimum of the potential energy function is searched using the genetic algorithm. The proposed algorithm first locates initial chromosomes at some locations within the pocket recognized according to the local shape of the β-shape. Then, the algorithm proceeds generations by taking advantage of powerful properties of the β-shape to achieve an extremely fast and good solution. We claim that the proposed method is much faster than other popular docking softwares including AutoDock.

  20. Cloud Computing for Protein-Ligand Binding Site Comparison

    Science.gov (United States)

    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. PMID:23762824

  1. 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)

  2. Efficient mapping of ligand migration channel networks in dynamic proteins.

    Science.gov (United States)

    Lin, Tu-Liang; Song, Guang

    2011-08-01

    For many proteins such as myoglobin, the binding site lies in the interior, and there is no obvious route from the exterior to the binding site in the average structure. Although computer simulations for a limited number of proteins have found some transiently open channels, it is not clear if there exist more channels elsewhere or how the channels are regulated. A systematic approach that can map out the whole ligand migration channel network is lacking. Ligand migration in a dynamic protein resembles closely a well-studied problem in robotics, namely, the navigation of a mobile robot in a dynamic environment. In this work, we present a novel robotic motion planning inspired approach that can map the ligand migration channel network in a dynamic protein. The method combines an efficient spatial mapping of protein inner space with a temporal exploration of protein structural heterogeneity, which is represented by a structure ensemble. The spatial mapping of each conformation in the ensemble produces a partial map of protein inner cavities and their inter-connectivity. These maps are then merged to form a super map that contains all the channels that open dynamically. Results on the pathways in myoglobin for gaseous ligands demonstrate the efficiency of our approach in mapping the ligand migration channel networks. The results, obtained in a significantly less amount of time than trajectory-based approaches, are in agreement with previous simulation results. Additionally, the method clearly illustrates how and what conformational changes open or close a channel.

  3. Cloud Computing for Protein-Ligand Binding Site Comparison

    Directory of Open Access Journals (Sweden)

    Che-Lun Hung

    2013-01-01

    Full Text Available 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.

  4. Conformational dynamics of a ligand-free adenylate kinase.

    Directory of Open Access Journals (Sweden)

    Hyun Deok Song

    Full Text Available Adenylate kinase (AdK is a phosphoryl-transfer enzyme with important physiological functions. Based on a ligand-free open structure and a ligand-bound closed structure solved by crystallography, here we use molecular dynamics simulations to examine the stability and dynamics of AdK conformations in the absence of ligands. We first perform multiple simulations starting from the open or the closed structure, and observe their free evolutions during a simulation time of 100 or 200 nanoseconds. In all seven simulations starting from the open structure, AdK remained stable near the initial conformation. The eight simulations initiated from the closed structure, in contrast, exhibited large variation in the subsequent evolutions, with most (seven undergoing large-scale spontaneous conformational changes and approaching or reaching the open state. To characterize the thermodynamics of the transition, we propose and apply a new sampling method that employs a series of restrained simulations to calculate a one-dimensional free energy along a curved pathway in the high-dimensional conformational space. Our calculated free energy profile features a single minimum at the open conformation, and indicates that the closed state, with a high (∼13 kcal/mol free energy, is not metastable, consistent with the observed behaviors of the unrestrained simulations. Collectively, our simulations suggest that it is energetically unfavorable for the ligand-free AdK to access the closed conformation, and imply that ligand binding may precede the closure of the enzyme.

  5. Insights into Protein–Ligand Interactions: Mechanisms, Models, and Methods

    Directory of Open Access Journals (Sweden)

    Xing Du

    2016-01-01

    Full Text Available Molecular recognition, which is the process of biological macromolecules interacting with each other or various small molecules with a high specificity and affinity to form a specific complex, constitutes the basis of all processes in living organisms. Proteins, an important class of biological macromolecules, realize their functions through binding to themselves or other molecules. A detailed understanding of the protein–ligand interactions is therefore central to understanding biology at the molecular level. Moreover, knowledge of the mechanisms responsible for the protein-ligand recognition and binding will also facilitate the discovery, design, and development of drugs. In the present review, first, the physicochemical mechanisms underlying protein–ligand binding, including the binding kinetics, thermodynamic concepts and relationships, and binding driving forces, are introduced and rationalized. Next, three currently existing protein-ligand binding models—the “lock-and-key”, “induced fit”, and “conformational selection”—are described and their underlying thermodynamic mechanisms are discussed. Finally, the methods available for investigating protein–ligand binding affinity, including experimental and theoretical/computational approaches, are introduced, and their advantages, disadvantages, and challenges are discussed.

  6. 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.

  7. 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.

  8. Synthesis, structure characterization and biological activity of selected metal complexes of sulfonamide Schiff base as a primary ligand and some mixed ligand complexes with glycine as a secondary ligand

    Science.gov (United States)

    Sharaby, Carmen M.; Amine, Mona F.; Hamed, Asmaa A.

    2017-04-01

    The current work reports synthesis of metal complexes and mixed ligand complexes of a novel sulfonamide Schiff base ligand (HL) resulted from the condensation of sulfametrole [N‧-(4-methoxy-1,2,5-thiadiazol-3-yl]sulfanilamide and acetyl-acetone as a primary ligand and glycine as a secondary ligand. The metal complexes and mixed ligand complexes of HL Schiff base ligand were synthesized and characterized using different physicochemical studies as elemental analyses, mass spectra, conductivity measurement, IR spectra, 1H NMR spectra, UV-vis Spectra, solid reflectance, magnetic susceptibility, thermal analyses (TGA and DTA) and their microbial and anticancer activities. The spectroscopic data of the complexes suggest their 1:2(L1:M) complex structures and 1:2:2(L1:L2:M) mixed ligand complex structures, where L1 = HL and L2 = glycine. Also, the spectroscopic studies suggested the octahedral structure for all complexes. The synthesized Schiff base, its metal and mixed ligand complexes were screened for their bacterial, antifungal and anticancer activity. The activity data show that the metal complexes and mixed ligand complexes exhibited promising microbial and anticancer activities than their parent HL Schiff base ligand, also the data show that the mixed ligand complexes more effective than the metal complexes.

  9. Memetic algorithms for ligand expulsion from protein cavities

    CERN Document Server

    Rydzewski, Jakub

    2015-01-01

    Ligand diffusion through a protein interior is a fundamental process governing biological signaling and enzymatic catalysis. A complex topology of channels in proteins leads often to difficulties in modeling ligand escape pathways by classical molecular dynamics simulations. In this paper two novel memetic methods for searching the exit paths and cavity space exploration are proposed: Memory Enhanced Random Acceleration (MERA) Molecular Dynamics and Immune Algorithm (IA). In MERA, a pheromone concept is introduced to optimize an expulsion force. In IA, hybrid learning protocols are exploited to predict ligand exit paths. They are tested on three protein channels with increasing complexity: M2 muscarinic GPCR receptor, enzyme nitrile hydratase and heme-protein cytochrome P450cam. In these cases, the memetic methods outperform Simulated Annealing and Random Acceleration Molecular Dynamics. The proposed algorithms are general and appropriate in all problems where an accelerated transport of an object through a n...

  10. Coordination chemistry of N-heterocyclic nitrenium-based ligands.

    Science.gov (United States)

    Tulchinsky, Yuri; Kozuch, Sebastian; Saha, Prasenjit; Mauda, Assaf; Nisnevich, Gennady; Botoshansky, Mark; Shimon, Linda J W; Gandelman, Mark

    2015-05-04

    Comprehensive studies on the coordination properties of tridentate nitrenium-based ligands are presented. N-heterocyclic nitrenium ions demonstrate general and versatile binding abilities to various transition metals, as exemplified by the synthesis and characterization of Rh(I) , Rh(III) , Mo(0) , Ru(0) , Ru(II) , Pd(II) , Pt(II) , Pt(IV) , and Ag(I) complexes based on these unusual ligands. Formation of nitrenium-metal bonds is unambiguously confirmed both in solution by selective (15) N-labeling experiments and in the solid state by X-ray crystallography. The generality of N-heterocyclic nitrenium as a ligand is also validated by a systematic DFT study of its affinity towards all second-row transition and post-transition metals (Y-Cd) in terms of the corresponding bond-dissociation energies.

  11. Advances Towards The Discovery of GPR55 Ligands.

    Science.gov (United States)

    Morales, Paula; Jagerovic, Nadine

    2016-01-01

    The G-protein-coupled receptor 55 (GPR55) was identified in 1999. It was proposed as a novel member of the endocannabinoid system due to the fact that some endogenous, plant-derived and synthetic cannabinoid ligands act on GPR55. However, the complexity of the cellular downstream signaling pathways related to GPR55 activation delayed the discovery of selective GPR55 ligands. It was only a few years ago that the high throughput screening of libraries of pharmaceutical companies and governmental organizations allowed to identify selective GPR55 agonists and antagonists. Since then, several GPR55 modulator scaffolds have been reported. The relevance of GPR55 has been explored in diverse physiological and pathological processes revealing its role in inflammation, neuropathic pain, bone physiology, diabetes and cancer. Considering GPR55 as a new promising therapeutic target, there is a clear need for new selective and potent GPR55 modulators. This review will address a current structural update of GPR55 ligands.

  12. CBS domains: Ligand binding sites and conformational variability.

    Science.gov (United States)

    Ereño-Orbea, June; Oyenarte, Iker; Martínez-Cruz, Luis Alfonso

    2013-12-01

    Cystathionine β-synthase (CBS) domains or CBS motifs are conserved structural domains that are present in thousands of non functionally-related proteins from all kingdoms of life. Their importance is underlined by the range of hereditary diseases associated with mutations in their amino acid sequence. CBS motifs associate in pairs referred to as Bateman modules. In contrast with initial assumptions, it is now well documented that CBS motifs and/or Bateman modules may suffer conformational changes upon binding of adenosine derivatives, metal ions or nucleic acids. The degree and direction of these structural changes depend on the type of ligand, the intrinsic features of the binding sites and the association manner of the Bateman modules. This review aims to provide a summary of the current knowledge on the structural basis of ligand recognition and on the structural effects caused by these ligands in CBS domain containing proteins. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. The Parathyroid Hormone Family of Ligands and Receptors

    Directory of Open Access Journals (Sweden)

    Damian G. D'Souza

    2015-07-01

    Full Text Available The PTH family of ligands and receptors have a wide range of vital functions from calcium homeostasis to tissue and bone development from the embryo to adult. This family has undergone whole genome duplication events predating vertebrate evolution, indicating more primitive and ancient functions other than skeletal development. The N-terminal region of the ligands, have been widely studied by biophysical and functional analysis, resulting in the discovery of key characteristics essential for ligand-receptor activation being elucidated. Multi-substituted amino acid analogs with differential binding affinities and either antagonistic or agonistic signalling potencies have been created based on these findings allowing for improvement on potential therapies affected by the PTH system in skeletal and embryonic development. The PTH family has diversely evolved to cover a wide range of pivotal pathways crucial to growth and development throughout all animal life.

  14. Protecting Ligands Enhance Selective Targeting of Multivalent Nanoparticles

    CERN Document Server

    Angioletti-Uberti, Stefano

    2016-01-01

    Nanoparticles functionalized with multiple ligands can be programmed to bind biological targets, e.g. cells, depending on the receptors they express, providing a general platform for the development of different technologies, from selective drug-delivery to biosensing. In order to be highly selective ligands should exclusively bind to specific targeted receptors, since formation of bonds with other, untargeted ones would lead to non-specific binding and potentially harmful behaviour. This poses a particular problem for multivalent nanoparticles, because even very weak bonds can collectively lead to strong binding. A statistical mechanical model is presented here to describe the extent to which bond strength and nanoparticle valency can induce non-selective adsorption. The same model is used to describe a possible solution: functionalization of the nanoparticles with "protective" receptors. The latter compete with cell receptors for the targeting ligands, and can be optimized to strongly reduce the effect of u...

  15. Activation of Neuropeptide FF Receptors by Kisspeptin Receptor Ligands.

    Science.gov (United States)

    Oishi, Shinya; Misu, Ryosuke; Tomita, Kenji; Setsuda, Shohei; Masuda, Ryo; Ohno, Hiroaki; Naniwa, Yousuke; Ieda, Nahoko; Inoue, Naoko; Ohkura, Satoshi; Uenoyama, Yoshihisa; Tsukamura, Hiroko; Maeda, Kei-Ichiro; Hirasawa, Akira; Tsujimoto, Gozoh; Fujii, Nobutaka

    2011-01-13

    Kisspeptin is a member of the RFamide neuropeptide family that is implicated in gonadotropin secretion. Because kisspeptin-GPR54 signaling is implicated in the neuroendocrine regulation of reproduction, GPR54 ligands represent promising therapeutic agents against endocrine secretion disorders. In the present study, the selectivity profiles of GPR54 agonist peptides were investigated for several GPCRs, including RFamide receptors. Kisspeptin-10 exhibited potent binding and activation of neuropeptide FF receptors (NPFFR1 and NPFFR2). In contrast, short peptide agonists bound with much lower affinity to NPFFRs while showing relatively high selectivity toward GPR54. The possible localization of secondary kisspeptin targets was also demonstrated by variation in the levels of GnRH release from the median eminence and the type of GPR54 agonists used. Negligible affinity of the reported NPFFR ligands to GPR54 was observed and indicates the unidirectional cross-reactivity between both ligands.

  16. Ligand Binding Thermodynamics in Drug Discovery: Still a Hot Tip?

    Science.gov (United States)

    Geschwindner, Stefan; Ulander, Johan; Johansson, Patrik

    2015-08-27

    The use of ligand binding thermodynamics has been proposed as a potential success factor to accelerate drug discovery. However, despite the intuitive appeal of optimizing binding enthalpy, a number of factors complicate routine use of thermodynamic data. On a macroscopic level, a range of experimental parameters including temperature and buffer choice significantly influence the observed thermodynamic signatures. On a microscopic level, solute effects, structural flexibility, and cooperativity lead to nonlinear changes in enthalpy. This multifactorial character hides essential enthalpy contributions of intermolecular contacts, making them experimentally nonobservable. In this perspective, we present three case studies, reflect on some key factors affecting thermodynamic signatures, and investigate their relation to the hydrophobic effect, enthalpy-entropy compensation, lipophilic ligand efficiency, and promiscuity. The studies highlight that enthalpy and entropy cannot be used as direct end points but can together with calculations increase our understanding of ligand binding and identify interesting outliers that do not behave as expected.

  17. Effect of ligands on thermal dissipation from gold nanorods.

    Science.gov (United States)

    Alper, Joshua; Hamad-Schifferli, Kimberly

    2010-03-16

    Thermal interface conductance was measured for soluble gold nanorods (NRs) coated with mercaptocarboxylic acids (HS-(CH(2))(n)COOH, n = 5, 10, 15), thiolated polyethylene glycols (MW = 356, 1000, 5000), and HS-(CH(2))(15)-COOH-coated NRs further coated with alternating layers of poly(diallyldimethylammonium chloride) and poly(sodium styrenesulfonate). Ferguson analysis determined ligand thickness. The thermal-diffusion-dominated regime of transient absorption spectra was fit to a continuum heat diffusion finite element model to obtain the thermal interface conductance, G, which varied with ligand chemistry but not molecule length. The results suggest that the ability to exclude water from the NR surface governs ligand G values.

  18. Pharmacokinetics and Pharmacodynamics of Nonsteroidal Androgen Receptor Ligands

    Science.gov (United States)

    Gao, Wenqing; Kim, Juhyun; Dalton, James T.

    2007-01-01

    Testosterone and structurally related anabolic steroids have been used to treat hypogonadism, muscle wasting, osteoporosis, male contraception, cancer cachexia, anemia, and hormone replacement therapy in aging men or age-related frailty; while antiandrogens may be useful for treatment of conditions like acne, alopecia (male-pattern baldness), hirsutism, benign prostatic hyperplasia (BPH) and prostate cancer. However, the undesirable physicochemical and pharmacokinetic properties of steroidal androgen receptor (AR) ligands limited their clinical use. Nonsteroidal AR ligands with improved pharmacological and pharmacokinetic properties have been developed to overcome these problems. This review focuses on the pharmacokinetics, metabolism, and pharmacology of clinically used and emerging nonsteroidal AR ligands, including antagonists, agonists, and selective androgen receptor modulators. PMID:16841196

  19. 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.

  20. GPCR biased ligands as novel heart failure therapeutics.

    Science.gov (United States)

    Violin, Jonathan D; Soergel, David G; Boerrigter, Guido; Burnett, John C; Lark, Michael W

    2013-10-01

    G protein-coupled receptors have been successfully targeted by numerous therapeutics including drugs that have transformed the management of cardiovascular disease. However, many GPCRs, when activated or blocked by drugs, elicit both beneficial and adverse pharmacology. Recent work has demonstrated that in some cases, the salutary and deleterious signals linked to a specific GPCR can be selectively targeted by "biased ligands" that entrain subsets of a receptor's normal pharmacology. This review briefly summarizes the advances and current state of the biased ligand field, focusing on an example: biased ligands targeting the angiotensin II type 1 receptor. These compounds exhibit unique pharmacology, distinct from classic agonists or antagonists, and one such molecule is now in clinical development for the treatment of acute heart failure.

  1. Memetic algorithms for ligand expulsion from protein cavities

    Science.gov (United States)

    Rydzewski, J.; Nowak, W.

    2015-09-01

    Ligand diffusion through a protein interior is a fundamental process governing biological signaling and enzymatic catalysis. A complex topology of channels in proteins leads often to difficulties in modeling ligand escape pathways by classical molecular dynamics simulations. In this paper, two novel memetic methods for searching the exit paths and cavity space exploration are proposed: Memory Enhanced Random Acceleration (MERA) Molecular Dynamics (MD) and Immune Algorithm (IA). In MERA, a pheromone concept is introduced to optimize an expulsion force. In IA, hybrid learning protocols are exploited to predict ligand exit paths. They are tested on three protein channels with increasing complexity: M2 muscarinic G-protein-coupled receptor, enzyme nitrile hydratase, and heme-protein cytochrome P450cam. In these cases, the memetic methods outperform simulated annealing and random acceleration molecular dynamics. The proposed algorithms are general and appropriate in all problems where an accelerated transport of an object through a network of channels is studied.

  2. 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.

  3. Evaluation of nanoparticle-ligand distributions to determine nanoparticle concentration.

    Science.gov (United States)

    Uddayasankar, Uvaraj; Shergill, Ravi T; Krull, Ulrich J

    2015-01-20

    The concentration of nanoparticles in solution is an important, yet challenging, parameter to quantify. In this work, a facile strategy for the determination of nanoparticle concentration is presented. The method relies on the quantitative analysis of the inherent distribution of nanoparticle-ligand conjugates that are generated when nanoparticles are functionalized with ligands. Validation of the method was accomplished by applying it to gold nanoparticles and semiconductor nanoparticles (CdSe/ZnS; core/shell). Poly(ethylene glycol) based ligands, with functional groups that quantitatively react with the nanoparticles, were incubated with the nanoparticles at varying equivalences. Agarose gel electrophoresis was subsequently used to separate and quantify the nanoparticle-ligand conjugates of varying valences. The distribution in the nanoparticle-ligand conjugates agreed well with that predicted by the Poisson model. A protocol was then developed, where a series of only eight different ligand amounts could provide an estimate of the nanoparticle concentration that spans 3 orders of magnitude (1 μM to 1 mM). For the gold nanoparticles and semiconductor nanoparticles, the measured concentrations were found to deviate by only 7% and 2%, respectively, from those determined by UV-vis spectroscopy. The precision of the assay was evaluated, resulting in a coefficient of variation of 5-7%. Finally, the protocol was used to determine the extinction coefficient of alloyed semiconductor nanoparticles (CdSxSe1-x/ZnS), for which a reliable estimate is currently unavailable, of three different emission wavelengths (525, 575, and 630 nm). The extinction coefficient of the nanoparticles of all emission wavelengths was similar and was found to be 2.1 × 10(5) M(-1)cm(-1).

  4. Ligand migration between internal docking sites in photodissociated carbonmonoxy neuroglobin.

    Science.gov (United States)

    Lutz, Stephan; Nienhaus, Karin; Nienhaus, G Ulrich; Meuwly, Markus

    2009-11-19

    Neuroglobin (Ngb) belongs to the large family of globular heme proteins capable of binding small gaseous ligands such as O(2), CO, or NO within their active site. In this work, we have analyzed CO migration pathways in photolyzed NgbCO using molecular dynamics (MD) simulations in combination with Fourier transform infrared temperature derivative spectroscopy (FTIR-TDS). A total of 55 ns of MD simulation was analyzed to explore the approximately 300 A(3) internal Ngb cavity. Overall, the simulations differentiated between eight possible docking sites, three of which were also identified experimentally. Low-temperature FTIR-TDS experiments on wild-type (wt) and F28W mutant NgbCO revealed that a small fraction of ligands migrates from site B to site C from which they rebound after slow cool illumination. For the F28L mutant, however, population of site C was not observed. In agreement with these findings, the simulations at 20 K showed ligand transfer between sites B and C for wt Ngb, but not for the F28L mutant. The ligand migration network could be mapped out and two key gate residues, Phe28 and Pro52, were identified. Ligand population analysis from the MD simulations revealed a direct relation between the size of the B10 side chain (Phe28 in wild-type Ngb) and the barrier against migration. Barriers for the transition of photodissociated CO from the distal pocket to the Xe4 site in Ngb are lower by up to 4 kcal/mol compared to myoglobin, suggesting that ligand migration between different docking sites is more facile in Ngb than in myoglobin.

  5. Isothermal Titration Calorimetry: Assisted Crystallization of RNA-Ligand Complexes.

    Science.gov (United States)

    Da Veiga, Cyrielle; Mezher, Joelle; Dumas, Philippe; Ennifar, Eric

    2016-01-01

    The success rate of nucleic acids/ligands co-crystallization can be significantly improved by performing preliminary biophysical analyses. Among suitable biophysical approaches, isothermal titration calorimetry (ITC) is certainly a method of choice. ITC can be used in a wide range of experimental conditions to monitor in real time the formation of the RNA- or DNA-ligand complex, with the advantage of providing in addition the complete binding profile of the interaction. Following the ITC experiment, the complex is ready to be concentrated for crystallization trials. This chapter describes a detailed experimental protocol for using ITC as a tool for monitoring RNA/small molecule binding, followed by co-crystallization.

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

    Directory of Open Access Journals (Sweden)

    Beda Brichacek

    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.

  7. Two ligands for a GPCR, proton vs lysolipid

    Institute of Scientific and Technical Information of China (English)

    Dong-soon IM

    2005-01-01

    Recently, two different chemicals have been matched as ligands with the same Gprotein-coupled receptor (GPCR). Double-pairing of OGR1 family GPCRs with proton and lysolipid raises several questions. First, whether both are the real ligands for the GPCRs. Second, whether modulation of a GPCR by two chemicals could be possible. Third, one of the chemicals is proton. Proton-sensing not only is a new action mode of GPCR activation, but also it could be generalized in other GPCRs.In this review, I'd like to summarize the issue and discuss questions with pharmacological criteria.

  8. Development of catalysts and ligands for enantioselective gold catalysis.

    Science.gov (United States)

    Wang, Yi-Ming; Lackner, Aaron D; Toste, F Dean

    2014-03-18

    During the past decade, the use of Au(I) complexes for the catalytic activation of C-C π-bonds has been investigated intensely. Over this time period, the development of homogeneous gold catalysis has been extraordinarily rapid and has yielded a host of mild and selective methods for the formation of carbon-carbon and carbon-heteroatom bonds. The facile formation of new bonds facilitated by gold naturally led to efforts toward rendering these transformations enantioselective. In this Account, we survey the development of catalysts and ligands for enantioselective gold catalysis by our research group as well as related work by others. We also discuss some of our strategies to address the challenges of enantioselective gold(I) catalysis. Early on, our work with enantioselective gold-catalyzed transformations focused on bis(phosphinegold) complexes derived from axially chiral scaffolds. Although these complexes were highly successful in some reactions like cyclopropanation, the careful choice of the weakly coordinating ligand (or counterion) was necessary to obtain high levels of enantioselectivity for the case of allene hydroamination. These counterion effects led us to use the anion itself as a source of chirality, which was successful in the case of allene hydroalkoxylation. In general, these tactics enhance the steric influence around the reactive gold center beyond the two-coordinate ligand environment. The use of binuclear complexes allowed us to use the second gold center and its associated ligand (or counterion) to exert a further steric influence. In a similar vein, we employed a chiral anion (in place of or in addition to a chiral ligand) to move the chiral information closer to the reactive center. In order to expand the scope of reactions amenable to enantioselective gold catalysis to cycloadditions and other carbocyclization processes, we also developed a new class of mononuclear phosphite and phosphoramidite ligands to supplement the previously widely

  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. Structural Basis of Cooperative Ligand Binding by the Glycine Riboswitch

    Energy Technology Data Exchange (ETDEWEB)

    E Butler; J Wang; Y Xiong; S Strobel

    2011-12-31

    The glycine riboswitch regulates gene expression through the cooperative recognition of its amino acid ligand by a tandem pair of aptamers. A 3.6 {angstrom} crystal structure of the tandem riboswitch from the glycine permease operon of Fusobacterium nucleatum reveals the glycine binding sites and an extensive network of interactions, largely mediated by asymmetric A-minor contacts, that serve to communicate ligand binding status between the aptamers. These interactions provide a structural basis for how the glycine riboswitch cooperatively regulates gene expression.

  11. Benzodiazepine receptor ligands: a patent review (2006 -- 2012)

    OpenAIRE

    2013-01-01

    Introduction: Ligands at the benzodiazepine site of the GABAA receptor (GABAA-R) act by modulating the effect of GABAA (g-aminobutyric acid). The selective modulator effects of such ligands are related to the a-subunits type (i.e., a1, a2, a3, and a5), being shown that the a1 subunit is associated with sedative, anticonvulsant and amnesic effects; whereas the a2 and a3 subunits mediate anxiolytic and myorelaxant effects. Recently it was shown the involvement of a5 subunit in...

  12. Rhodium catalyzed asymmetric Pauson-Khand reaction using SDP ligands

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The activity and enantiocontrol ability of the chiral catalysts prepared from spiro diphosphine ligands, SDP, and rhodium precursor were investigated in the asymmetric catalytic Pauson-Khand reaction. The results showed that SDP ligands were very effective in Rh-catalyzed Pauson-Khand reaction, and their complexes with rhodium could convert a variety of 1,6-enyne compounds into bicyclopentone derivatives under CO atmosphere in high yields with good enantioselectivities. The SbF6- was found to be a suitable counter anion of the catalyst, and 1,2-dichloroethane was the best choice of the solvent for Pauson-Khand reaction.

  13. 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.

  14. Methods for Identifying Ligands that Target Nucleic Acid Molecules and Nucleic Acid Structural Motifs

    Science.gov (United States)

    Disney, Matthew D. (Inventor); Childs-Disney, Jessica L. (Inventor)

    2017-01-01

    Disclosed are methods for identifying a nucleic acid (e.g., RNA, DNA, etc.) motif which interacts with a ligand. The method includes providing a plurality of ligands immobilized on a support, wherein each particular ligand is immobilized at a discrete location on the support; contacting the plurality of immobilized ligands with a nucleic acid motif library under conditions effective for one or more members of the nucleic acid motif library to bind with the immobilized ligands; and identifying members of the nucleic acid motif library that are bound to a particular immobilized ligand. Also disclosed are methods for selecting, from a plurality of candidate ligands, one or more ligands that have increased likelihood of binding to a nucleic acid molecule comprising a particular nucleic acid motif, as well as methods for identifying a nucleic acid which interacts with a ligand.

  15. From α4β2 Nicotinic Ligands to the Discovery of σ1 Receptor Ligands: Pharmacophore Analysis and Rational Design.

    Science.gov (United States)

    Yu, Li-Fang; Zhang, Han-Kun; Gunosewoyo, Hendra; Kozikowski, Alan P

    2012-12-13

    Comparative analyses of the pharmacophoric elements required for σ1 and nicotinic ligands led to the identification of a potent and selective σ1 ligand (15). Compound 15 displayed high selectivity for the σ1 receptor (Ki, σ1 = 4.1 nM, Ki, σ2 = 1312 nM) with moderate binding affinity for the DAT (Ki = 373 nM) and NET (Ki = 203 nM) in the PDSP broad screening panel of common CNS neurotransmitter transporters and receptors. The key finding in this present work is that a subtle structural modifica tion could be used as a tool to switch a ligand's selectivity between nAChRs and sigma receptors.

  16. Seven-coordinate iridium(V) polyhydrides with chelating bis(silyl) ligands

    Energy Technology Data Exchange (ETDEWEB)

    Loza, M.; Faller, J.W.; Crabtree, R.H. [Yale Univ., New Haven, CT (United States)

    1995-05-24

    The pentahydride IrH{sub 5}(PPh{sub 3}){sub 2} reacts with chelating silanes with loss of H{sub 2} to form the classical seven-coordinate distorted pentagonal bipyramidal silyl polyhydride complexes IrH{sub 3}(disil)(PPh{sub 3}){sub 2}(disil: dmsb, 3a; tids, 3b) with monodentate silanes to give IrH{sub 4}(SiR{sub 3})(PPh{sub 3}){sub 2} (R: Et, 4a; Ph, 4b) and with triphenyltin hydride to give IrH{sub 3{minus}} (SnPh{sub 3}){sup 2}(PPh{sub 3}){sub 2} (5), all rare examples of Ir(V). A crystal structure was obtained for 3a. Crystal data: orthorhombic; space group Pbca (No. 61); a = 17.1534(6) {Angstrom}; b = 25.688(2) {Angstrom}; c = 19.0641(9) {Angstrom}; V=8400(1) {Angstrom}{sup 3}; Z=8.

  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. Predicting Electrophoretic Mobility of Protein-Ligand Complexes for Ligands from DNA-Encoded Libraries of Small Molecules.

    Science.gov (United States)

    Bao, Jiayin; Krylova, Svetlana M; Cherney, Leonid T; Hale, Robert L; Belyanskaya, Svetlana L; Chiu, Cynthia H; Shaginian, Alex; Arico-Muendel, Christopher C; Krylov, Sergey N

    2016-05-17

    Selection of target-binding ligands from DNA-encoded libraries of small molecules (DELSMs) is a rapidly developing approach in drug-lead discovery. Methods of kinetic capillary electrophoresis (KCE) may facilitate highly efficient homogeneous selection of ligands from DELSMs. However, KCE methods require accurate prediction of electrophoretic mobilities of protein-ligand complexes. Such prediction, in turn, requires a theory that would be applicable to DNA tags of different structures used in different DELSMs. Here we present such a theory. It utilizes a model of a globular protein connected, through a single point (small molecule), to a linear DNA tag containing a combination of alternating double-stranded and single-stranded DNA (dsDNA and ssDNA) regions of varying lengths. The theory links the unknown electrophoretic mobility of protein-DNA complex with experimentally determined electrophoretic mobilities of the protein and DNA. Mobility prediction was initially tested by using a protein interacting with 18 ligands of various combinations of dsDNA and ssDNA regions, which mimicked different DELSMs. For all studied ligands, deviation of the predicted mobility from the experimentally determined value was within 11%. Finally, the prediction was tested for two proteins and two ligands with a DNA tag identical to those of DELSM manufactured by GlaxoSmithKline. Deviation between the predicted and experimentally determined mobilities did not exceed 5%. These results confirm the accuracy and robustness of our model, which makes KCE methods one step closer to their practical use in selection of drug leads, and diagnostic probes from DELSMs.

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

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Ke-Li; Zhang, Yi-Ping; Cai, Yi-Ni; Xu, Xiao-Wei; Feng, Yun-Long, E-mail: sky37@zjnu.cn

    2014-07-01

    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{sub 2}(H{sub 2}O){sub 2}]{sub n}·2nH{sub 2}O (1), which possesses a 1D chain structure. In the presence of ancillary ligands, namely, 1,3-adamantanedicarboxylic acid (H{sub 2}adbc), terephthalic acid (H{sub 2}tpa), thiophene-2,5-dicarboxylic acid (H{sub 2}tdc) and 1,4-benzenedithioacetic acid (H{sub 2}bdtc), four 3D structures [Co{sub 2}L{sub 2}(adbc)]{sub n}·nH{sub 2}O (2), [Co{sub 2}L{sub 2}(tpa)]{sub n} (3), [Co{sub 2}L{sub 2}(tdc)]{sub n} (4), [Co{sub 2}L{sub 2}(bdtc)(H{sub 2}O)]{sub 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.

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

    DEFF Research Database (Denmark)

    Pedersen, Christian Storm; Kristensen, Thomas Greve

    When designing novel drugs, the need arise to screen databases for structures resembling active ligands, e.g. by generating a query meta-structure which summarizes these. We propose a flexible bond method for making a meta-structure and present Monte Carlo, Nelder-Mead and Differential Evolution ...

  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. Towards organometallic conducting polymers containing bis-cyclometallating bridging ligands

    NARCIS (Netherlands)

    Koten, G. van; Sutter, J-P; Beley, M.; Collin, J.P.; Veldman, N.; Spek, A.L.; Sauvage, J.P.

    1994-01-01

    One dimensional polymeric structures (rods and wires) incorporating capping ends with either electron or accepting properties will be prepared and their electric and photophysical properties studied. The capping ends are based on metal centres held in bis-cyclometallating ligands with tuneable elec

  3. A response calculus for immobilized T cell receptor ligands

    DEFF Research Database (Denmark)

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

    2001-01-01

    To address the molecular mechanism of T cell receptor (TCR) signaling, we have formulated a model for T cell activation, termed the 2D-affinity model, in which the density of TCR on the T cell surface, the density of ligand on the presenting surface, and their corresponding two-dimensional affini...

  4. CLE peptide ligands and their roles in establishing meristems

    NARCIS (Netherlands)

    Fiers, M.A.; Ku, K.L.; Liu, C.M.

    2007-01-01

    Research in the past decade revealed that peptide ligands, also called peptide hormones, play a crucial role in intercellular communication and defense response in plants. Recent studies demonstrated that a family of plant-specific genes, CLAVATA3 (CLV3)/ENDOSPERM SURROUNDING REGION (ESR) (CLE),

  5. The imidazoline receptors and ligands in pain modulation

    Directory of Open Access Journals (Sweden)

    Nurcan Bektas

    2015-01-01

    Full Text Available Pain is an unpleasant experience and effects daily routine negatively. Although there are various drugs, many of them are not entirely successful in relieving pain, since pain modulation is a complex process involving numerous mediators and receptors. Therefore, it is a rational approach to identify the factors involved in the complex process and develop new agents that act on these pain producing mechanisms. In this respect, the involvement of the imidazoline receptors in pain modulation has drawn attention in recent years. In this review, it is aimed to focus on the imidazoline receptors and their ligands which contribute to the pain modulation. It is demonstrated that imidazoline-2 (I2 receptors are steady new drug targets for analgesics. Even if the mechanism of I2receptor is not well known in the modulation of pain, it is known that it plays a role in tonic and chronic pain but not in acute phasic pain. Moreover, the I2receptor ligands increase the analgesic effects of opioids in both acute and chronic pain and prevent the development of opioid tolerance. So, they are valuable for the chronic pain treatment and also therapeutic coadjuvants in the management of chronic pain with opiate drugs due to the attenuation of opioid tolerance and addiction. Thus, the use of the ligands which bind to the imidazoline receptors is an effective strategy for relieving pain. This educational forum exhibits the role of imidazoline receptors and ligands in pain process by utilizing experimental studies.

  6. Synthesis and Characterization of Heteropoly Coordination Compounds Containing Optical Ligands

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Introduction   The heteropolyanion phase transfer chemistry created by Pope M. T. In 1984 has opened up a new field for heteropoly compound research[1-3]. But substituting coordination water molecules by organic optically active ligand has not been reported in literatures until 1997[4].

  7. Design, synthesis and evaluation of multivalent glycodendrimers as multivalent ligands

    NARCIS (Netherlands)

    Branderhorst, H.M.

    2008-01-01

    Carbohydrates are more and more of interest in drug design as they are important mediators in a whole range of biological processes. Because of the low affinity of carbohydrates for their receptors, multivalent ligand presentation was introduced. Multivalent compounds were shown to improve the affin

  8. Local Innate Responses to TLR Ligands in the Chicken Trachea

    Directory of Open Access Journals (Sweden)

    Neda Barjesteh

    2016-07-01

    Full Text Available The chicken upper respiratory tract is the portal of entry for respiratory pathogens, such as avian influenza virus (AIV. The presence of microorganisms is sensed by pathogen recognition receptors (such as Toll-like receptors (TLRs of the innate immune defenses. Innate responses are essential for subsequent induction of potent adaptive immune responses, but little information is available about innate antiviral responses of the chicken trachea. We hypothesized that TLR ligands induce innate antiviral responses in the chicken trachea. Tracheal organ cultures (TOC were used to investigate localized innate responses to TLR ligands. Expression of candidate genes, which play a role in antiviral responses, was quantified. To confirm the antiviral responses of stimulated TOC, chicken macrophages were treated with supernatants from stimulated TOC, prior to infection with AIV. The results demonstrated that TLR ligands induced the expression of pro-inflammatory cytokines, type I interferons and interferon stimulated genes in the chicken trachea. In conclusion, TLR ligands induce functional antiviral responses in the chicken trachea, which may act against some pathogens, such as AIV.

  9. Multifunctional ligand for use as a diagnostic or therapeutic pharmaceutical

    Science.gov (United States)

    Katti, Kattesh V.; Volkert, Wynn A.; Ketring, Alan R.; Singh, Prahlad R.

    1996-01-01

    A compound and method of making a compound for use as a diagnostic or therapeutic pharmaceutical comprises either a phosphorous or germanium core and at least two hydrazine groups forming a ligand for bonding to a metal extending from the phosphorous or germanium core.

  10. Automated docking of flexible ligands: applications of AutoDock.

    Science.gov (United States)

    Goodsell, D S; Morris, G M; Olson, A J

    1996-01-01

    AutoDock is a suite of C programs used to predict the bound conformations of a small, flexible ligand to a macromolecular target of known structure. The technique combines simulated annealing for conformation searching with a rapid grid-based method of energy evaluation. This paper reviews recent applications of the technique and describes the enhancements included in the current release.

  11. Programmed death ligand 2 in cancer-induced immune suppression.

    NARCIS (Netherlands)

    Rozali, E.N.; Hato, S.V.; Robinson, B.W.; Lake, R.A.; Lesterhuis, W.J.

    2012-01-01

    Inhibitory molecules of the B7/CD28 family play a key role in the induction of immune tolerance in the tumor microenvironment. The programmed death-1 receptor (PD-1), with its ligands PD-L1 and PD-L2, constitutes an important member of these inhibitory pathways. The relevance of the PD-1/PD-L1 pathw

  12. 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.

  13. 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.

  14. NMR-based screening of membrane protein ligands

    NARCIS (Netherlands)

    Yanamala, Naveena; Dutta, Arpana; Beck, Barbara; Van Fleet, Bart; Hay, Kelly; Yazbak, Ahmad; Ishima, Rieko; Doemling, Alexander; Klein-Seetharaman, Judith

    2010-01-01

    Membrane proteins pose problems for the application of NMR-based ligand-screening methods because of the need to maintain the proteins in a membrane mimetic environment such as detergent micelles: they add to the molecular weight of the protein, increase the viscosity of the solution, interact with

  15. Supramolecular coordination and antimicrobial activities of constructed mixed ligand complexes

    Science.gov (United States)

    El-Sonbati, A. Z.; Diab, M. A.; El-Bindary, A. A.; Abou-Dobara, M. I.; Seyam, H. A.

    2013-03-01

    A novel series of copper(II) and palladium(II) with 4-derivatives benzaldehyde pyrazolone (Ln) were synthesized. The mixed ligand complexes were prepared by using 1,10-phenanthroline (Phen) as second ligand. The structure of these complexes was identified and confirm by elemental analysis, molar conductivity, UV-Vis, IR and 1H NMR spectroscopy and magnetic moment measurements as well as thermal analysis. The ligand behaves as a neutral bidentate ligand through ON donor sites. ESR spectra show the simultaneous presence of a planar trans and a nearly planar cis isomers in the 1:2 ratio for all N,O complexes [Cu(Ln)2]Cl2ṡ2H2O. Schiff bases (Ln) were tested against bacterial species; namely two Gram positive bacteria (Staphylococcus aureus and Bacillus cereus) and two Gram negative bacteria (Escherichia coli and Klebsiella pneumoniae) and fungal species (Aspergillus niger, Fusarium oxysporium, Penicillium italicum and Alternaria alternata). The tested compounds have antibacterial activity against S. aureus, B. cereus and K. pneumoniae.

  16. Titanium complex formation of organic ligands in titania gels.

    Science.gov (United States)

    Nishikiori, Hiromasa; Todoroki, Kenta; Setiawan, Rudi Agus; Teshima, Katsuya; Fujii, Tsuneo; Satozono, Hiroshi

    2015-01-27

    Thin films of organic ligand-dispersing titania gels were prepared from titanium alkoxide sols containing ligand molecules by steam treatment without heating. The formation of the ligand-titanium complex and the photoinduced electron transfer process in the systems were investigated by photoelectrochemical measurements. The complex was formed between the 8-hydroxyquinoline (HQ) and titanium species, such as the titanium ion, on the titania nanoparticle surface through the oxygen and nitrogen atoms of the quinolate. A photocurrent was observed in the electrodes containing the complex due to the electron injection from the LUMO of the complex into the titania conduction band. A bidentate ligand, 2,3-dihydroxynaphthalene (DHN), formed the complex on the titania surface through dehydration between its two hydroxyl groups of DHN and two TiOH groups of the titania. The electron injection from the HOMO of DHN to the titania conduction band was observed during light irradiation. This direct electron injection was more effective than the two-step electron injection.

  17. Hybrid diphosphorus ligands in rhodium catalysed asymmetric hydroformylation

    NARCIS (Netherlands)

    Chikkali, S.H.; van der Vlugt, J.I.; Reek, J.N.H.

    2014-01-01

    This review aims to illustrate recent advances in the application of hybrid diphosphorus ligands for the Rh catalysed hydroformylation of alkenes, discussing the most prevalent classes of hybrid systems, i.e. phosphine-phosphinite, phosphine-phosphonite, phosphine-phosphite, phosphite-phosphoramidit

  18. Ligand-targeted particulate nanomedicines undergoing clinical evaluations: current status

    NARCIS (Netherlands)

    Meel, van der Roy; Vehmeijer, Laurens J.C.; Kok, Robbert J.; Storm, Gert; Gaal, van Ethlinn V.B.

    2013-01-01

    Since the introduction of Doxil® on the market nearly 20 years ago, a number of nanomedicines have become part of treatment regimens in the clinic. With the exception of antibody–drug conjugates, these nanomedicines are all devoid of targeting ligands and rely solely on their physicochemical propert

  19. Colloidal-quantum-dot photovoltaics using atomic-ligand passivation

    Science.gov (United States)

    Tang, Jiang; Kemp, Kyle W.; Hoogland, Sjoerd; Jeong, Kwang S.; Liu, Huan; Levina, Larissa; Furukawa, Melissa; Wang, Xihua; Debnath, Ratan; Cha, Dongkyu; Chou, Kang Wei; Fischer, Armin; Amassian, Aram; Asbury, John B.; Sargent, Edward H.

    2011-10-01

    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.

  20. Synthesis and Characterization of Metal Complexes with Schiff Base Ligands

    Science.gov (United States)

    Wilkinson, Shane M.; Sheedy, Timothy M.; New, Elizabeth J.

    2016-01-01

    In order for undergraduate laboratory experiments to reflect modern research practice, it is essential that they include a range of elements, and that synthetic tasks are accompanied by characterization and analysis. This intermediate general chemistry laboratory exercise runs over 2 weeks, and involves the preparation of a Schiff base ligand and…

  1. Quantifying ligand effects in high-oxidation-state metal catalysis

    Science.gov (United States)

    Billow, Brennan S.; McDaniel, Tanner J.; Odom, Aaron L.

    2017-09-01

    Catalysis by high-valent metals such as titanium(IV) impacts our lives daily through reactions like olefin polymerization. In any catalysis, optimization involves a careful choice of not just the metal but also the ancillary ligands. Because these choices dramatically impact the electronic structure of the system and, in turn, catalyst performance, new tools for catalyst development are needed. Understanding ancillary ligand effects is arguably one of the most critical aspects of catalyst optimization and, while parameters for phosphines have been used for decades with low-valent systems, a comparable system does not exist for high-valent metals. A new electronic parameter for ligand donation, derived from experiments on a high-valent chromium species, is now available. Here, we show that the new parameters enable quantitative determination of ancillary ligand effects on catalysis rate and, in some cases, even provide mechanistic information. Analysing reactions in this way can be used to design better catalyst architectures and paves the way for the use of such parameters in a host of high-valent processes.

  2. 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

  3. Partial association of restriction polymorphism of the ligand binding ...

    African Journals Online (AJOL)

    Mohamed Hessien

    2015-11-02

    Nov 2, 2015 ... in the ligand binding domain (LBD) impair the receptor activity and play a crucial role in the devel- opment and .... Groups. Benign prostatic hyperplasia. Prostate cancer n. 15. 15. Age (yr) .... Frequency/cut position. Exon 4/5.

  4. Structural Analysis Uncovers Lipid-Binding Properties of Notch Ligands

    Directory of Open Access Journals (Sweden)

    Chandramouli R. Chillakuri

    2013-11-01

    Full Text Available The Notch pathway is a core cell-cell signaling system in metazoan organisms with key roles in cell-fate determination, stem cell maintenance, immune system activation, and angiogenesis. Signals are initiated by extracellular interactions of the Notch receptor with Delta/Serrate/Lag-2 (DSL ligands, whose structure is highly conserved throughout evolution. To date, no structure or activity has been associated with the extreme N termini of the ligands, even though numerous mutations in this region of Jagged-1 ligand lead to human disease. Here, we demonstrate that the N terminus of human Jagged-1 is a C2 phospholipid recognition domain that binds phospholipid bilayers in a calcium-dependent fashion. Furthermore, we show that this activity is shared by a member of the other class of Notch ligands, human Delta-like-1, and the evolutionary distant Drosophila Serrate. Targeted mutagenesis of Jagged-1 C2 domain residues implicated in calcium-dependent phospholipid binding leaves Notch interactions intact but can reduce Notch activation. These results reveal an important and previously unsuspected role for phospholipid recognition in control of this key signaling system.

  5. Optical control over bioactive ligands at supramolecular surfaces

    NARCIS (Netherlands)

    Voskuhl, Jens; Sankaran, S.; Jonkheijm, Pascal

    2014-01-01

    In this communication we report for the first time the use of azobenzene modified glycoconjugates to establish optical control over bioactive ligands at a supramolecular β-cyclodextrin (β-CD) surface. Several studies were conducted to investigate the photoresponsive immobilization of proteins and

  6. Ligand and ensemble effects in adsorption on alloy surfaces

    DEFF Research Database (Denmark)

    Liu, Ping; Nørskov, Jens Kehlet

    2001-01-01

    Density functional theory is used to study the adsorption of carbon monoxide, oxygen and nitrogen on various Au/Pd(111) bimetallic alloy surfaces. By varying the Au content in the surface we are able to make a clear separation into geometrical (or ensemble) effects and electronic (or ligand...

  7. Photocontrol over cooperative porphyrin self-assembly with phenylazopyridine ligands.

    Science.gov (United States)

    Hirose, Takashi; Helmich, Floris; Meijer, E W

    2013-01-02

    The cooperative self-assembly of chiral zinc porphyrins is regulated by a photoresponsive phenylazopyridine ligand. Porphyrin stacks depolymerize into dimers upon axial ligation and the strength of the coordination is regulated by its photoinduced isomerization, which shows more than 95 % conversion ratio for both photostationary states.

  8. Lead Generation and Optimization Based on Protein-Ligand Complementarity

    Directory of Open Access Journals (Sweden)

    Koji Ogata

    2010-06-01

    Full Text Available This work proposes a computational procedure for structure-based lead generation and optimization, which relies on the complementarity of the protein-ligand interactions. This procedure takes as input the known structure of a protein-ligand complex. Retaining the positions of the ligand heavy atoms in the protein binding site it designs structurally similar compounds considering all possible combinations of atomic species (N, C, O, CH3, NH,etc. Compounds are ranked based on a score which incorporates energetic contributions evaluated using molecular mechanics force fields. This procedure was used to design new inhibitor molecules for three serine/threonine protein kinases (p38 MAP kinase, p42 MAP kinase (ERK2, and c-Jun N-terminal kinase 3 (JNK3. For each enzyme, the calculations produce a set of potential inhibitors whose scores are in agreement with IC50 data and Ki values. Furthermore, the native ligands for each protein target, scored within the five top-ranking compounds predicted by our method, one of the top-ranking compounds predicted to inhibit JNK3 was synthesized and his inhibitory activity confirmed against ATP hydrolysis. Our computational procedure is therefore deemed to be a useful tool for generating chemically diverse molecules active against known target proteins.

  9. Central nicotinic receptors: structure, function, ligands, and therapeutic potential.

    Science.gov (United States)

    Romanelli, M Novella; Gratteri, Paola; Guandalini, Luca; Martini, Elisabetta; Bonaccini, Claudia; Gualtieri, Fulvio

    2007-06-01

    The growing interest in nicotinic receptors, because of their wide expression in neuronal and non-neuronal tissues and their involvement in several important CNS pathologies, has stimulated the synthesis of a high number of ligands able to modulate their function. These membrane proteins appear to be highly heterogeneous, and still only incomplete information is available on their structure, subunit composition, and stoichiometry. This is due to the lack of selective ligands to study the role of nAChR under physiological or pathological conditions; so far, only compounds showing selectivity between alpha4beta2 and alpha7 receptors have been obtained. The nicotinic receptor ligands have been designed starting from lead compounds from natural sources such as nicotine, cytisine, or epibatidine, and, more recently, through the high-throughput screening of chemical libraries. This review focuses on the structure of the new agonists, antagonists, and allosteric ligands of nicotinic receptors, it highlights the current knowledge on the binding site models as a molecular modeling approach to design new compounds, and it discusses the nAChR modulators which have entered clinical trials.

  10. Biosensors engineered from conditionally stable ligand-binding domains

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    DEFF Research Database (Denmark)

    Pedersen, Christian Storm; Kristensen, Thomas Greve

    When designing novel drugs, the need arise to screen databases for structures resembling active ligands, e.g. by generating a query meta-structure which summarizes these. We propose a flexible bond method for making a meta-structure and present Monte Carlo, Nelder-Mead and Differential Evolution...

  12. 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...

  13. COMPLEXES WITH TRIDENTATE N2,O-DONOR LIGAND

    African Journals Online (AJOL)

    been investigated towards several transition metal ions. .... high-spin Mn(II) complex with d5 configuration (S = 5/2) and shows an octahedral ... at short wavelengths, between 290 and 405 nm, may be assigned to ligand-metal ion charge.

  14. SPECIATION OF CADMIUM MIXED LIGAND COMPLEXES IN SALT ...

    African Journals Online (AJOL)

    a

    IN SALT WATER LAKES+ ... Most metals are toxic to living organisms and have a tendency to accumulate in ... and the other at 9.6 x 10-8 M, a much lower value. ... Table 1. Stability constants of carbonato/chloro mixed ligand complexes at ...

  15. 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...

  16. Fluorescent ligands for studying neuropeptide receptors by confocal microscopy

    Directory of Open Access Journals (Sweden)

    Beaudet A.

    1998-01-01

    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.

  17. 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.

  18. Docking validation resources: protein family and ligand flexibility experiments.

    Science.gov (United States)

    Mukherjee, Sudipto; Balius, Trent E; Rizzo, Robert C

    2010-11-22

    A database consisting of 780 ligand-receptor complexes, termed SB2010, has been derived from the Protein Databank to evaluate the accuracy of docking protocols for regenerating bound ligand conformations. The goal is to provide easily accessible community resources for development of improved procedures to aid virtual screening for ligands with a wide range of flexibilities. Three core experiments using the program DOCK, which employ rigid (RGD), fixed anchor (FAD), and flexible (FLX) protocols, were used to gauge performance by several different metrics: (1) global results, (2) ligand flexibility, (3) protein family, and (4) cross-docking. Global spectrum plots of successes and failures vs rmsd reveal well-defined inflection regions, which suggest the commonly used 2 Å criteria is a reasonable choice for defining success. Across all 780 systems, success tracks with the relative difficulty of the calculations: RGD (82.3%) > FAD (78.1%) > FLX (63.8%). In general, failures due to scoring strongly outweigh those due to sampling. Subsets of SB2010 grouped by ligand flexibility (7-or-less, 8-to-15, and 15-plus rotatable bonds) reveal that success degrades linearly for FAD and FLX protocols, in contrast to RGD, which remains constant. Despite the challenges associated with FLX anchor orientation and on-the-fly flexible growth, success rates for the 7-or-less (74.5%) and, in particular, the 8-to-15 (55.2%) subset are encouraging. Poorer results for the very flexible 15-plus set (39.3%) indicate substantial room for improvement. Family-based success appears largely independent of ligand flexibility, suggesting a strong dependence on the binding site environment. For example, zinc-containing proteins are generally problematic, despite moderately flexible ligands. Finally, representative cross-docking examples, for carbonic anhydrase, thermolysin, and neuraminidase families, show the utility of family-based analysis for rapid identification of particularly good or bad

  19. 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.

  20. Aryl hydrocarbon receptor ligand activity of commercial health foods.

    Science.gov (United States)

    Amakura, Yoshiaki; Tsutsumi, Tomoaki; Nakamura, Masafumi; Handa, Hiroshi; Yoshimura, Morio; Matsuda, Rieko; Yoshida, Takashi

    2011-06-15

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates toxicological effects by binding to agonists such as dioxins. We previously reported the presence of natural dioxin-like ligands in foods. To further characterise natural ligands with dioxin-like activity, we examined the influence of 50 kinds of commercial supplement and health food on the AhR, using a reporter gene assay. Some samples, prepared using soybean, sesame, or propolis as an ingredient, were revealed to show AhR-binding activity, similar to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), at high concentrations. To characterise the AhR-activating substances in eight active samples, the respective extracts were subjected to fractionation with n-hexane, ethyl acetate, and water, followed by estimating their AhR activities. The n-hexane fraction of the propolis extract sample, and the ethyl acetate fractions of the other samples, showed AhR activity similar to that of TCDD, at a high concentration range. HPLC analysis of the active fractions identified isoflavones, such as daidzein and glycitein, and flavones, such as tectochrysin and chrysin, in the samples. Among these compounds, tectochrysin exhibited marked AhR activation. Flavonoids, which are characterised as natural AhR ligands, are known to have representative beneficial effects on human health. The natural AhR ligands identified in this study are known to be useful for human health. Therefore, it is considered that AhR may play a beneficial regulatory role in humans. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Dissolved Mn Speciation and Ligand Characteristics in a Coastal Waterway

    Science.gov (United States)

    Oldham, V.; Jensen, L.; Luther, G. W., III

    2014-12-01

    Soluble manganese speciation (Mn(II) and Mn(III); 0.2 μm filtered) was measured along a salinity gradient in the Broadkill River, a coastal waterway bordered by wetlands and salt marshes in Delaware. We modified an established method of porphyrin (T-4(CP)P) addition, by incorporating a heating step and coupling a 100-cm cell to a UV/Vis detector, to achieve a 4.0 nM sample DL. Surface waters were collected from June to August, 2014 and total dissolved Mn (0.23 - 1.92 μM) first increased then decreased along the salinity gradient (31 ppt to freshwater). However, Mn speciation was highly variable; Mn(III) made up 0-49 % of the total dissolved Mn, where the highest Mn(III) values occurred at sites with high salt-marsh runoff. Mn(III) was not recoverable without the addition of a strong reducing agent, indicating that little or no weak ligand was present, and that a strong ligand was responsible for complexing Mn(III). An assessment of potential strong ligand character was made by precipitating humic matter, by acidifying subsamples to pHyellow color. Upon the addition of 500 μM desferrioxamine-B (DFOB) to the same sample, a peak at 310 nm appeared, indicating the formation of Mn(III)-DFOB. In acidified samples, the Mn(III)-pyrophosphate peak did not change. Humic matter, therefore, may be acting as an Mn(III) binding ligand, outcompeting pyrophosphate for Mn(III), however this natural ligand is outcompeted by a large excess of DFOB. The humic matter and increased Mn likely come from the salt marsh runoff during tidal exchange, and we observed that as salinity increased, the amount of humic binding decreased. These results present the first Mn speciation measurements along a salinity gradient in oxygenated waters.

  2. Heterobifunctional crosslinkers for tethering single ligand molecules to scanning probes

    Energy Technology Data Exchange (ETDEWEB)

    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

    2003-11-14

    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{sub 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{sub 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{sub 6}-tagged protein molecules to AFM tips via noncovalent NTA-Ni{sup 2+}-His{sub 6} bridges. The new crosslinker was applied to link a recombinant His{sub 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 {beta}1 was studied in detail by SMRFM, using the new crosslinker to link His{sub 6}-tagged Ran to the measuring tip [Nat. Struct. Biol. (2003), 10, 553-557].

  3. Investigations into the synthesis and fluorescence properties of Tb(III) complexes of a novel bis-beta-diketone-type ligand and a novel bispyrazole ligand.

    Science.gov (United States)

    Xiao, Lin-Xiang; Luo, Yi-Ming; Chen, Zhe; Li, Jun; Tang, Rui-Ren

    2008-11-15

    A novel bis-beta-diketone organic ligand, 1,1'-(2,6-bispyridyl)bis-3-(p-methoxyphenyl)-1,3-propanedione (L1) and its derivatives, a novel bispyrazole ligand, 2,6-bis(5-(4-methoxyphenyl)-1H-pyrazol-3-yl)pyridine (L2) were designed and synthesized and their complexes with Tb(III) ion were successfully prepared. The ligands and the corresponding metal complexes were characterized by elemental analysis, infrared, proton nuclear magnetic resonance spectroscopy and TG-DTA. Analysis of the IR spectra suggested that the lanthanide metal ion Tb(III) coordinated to the ligands via the nitrogen atom of the pyridine ring and the carbonyl oxygen atoms for ligand L1 and the nitrogen atom of the pyrazole ring for ligand L2. The fluorescence properties of the two complexes in solid state were investigated and it was discovered that the Tb(III) ions could be sensitized by both the ligand (L1) and ligand (L2) to some extent. In particular, the complex of ligand (L2) is a better green luminescent material that could be used as a candidate material in organic light-emitting devices (OLEDs) since it could be much better sensitized by the ligand (L2), and the fluorescence intensity of Tb(III) complex of L2 are almost as twice strong as L1's.

  4. Investigations into the synthesis and fluorescence properties of Tb(III) complexes of a novel bis-β-diketone-type ligand and a novel bispyrazole ligand

    Science.gov (United States)

    Xiao, Lin-Xiang; Luo, Yi-Ming; Chen, Zhe; Li, Jun; Tang, Rui-Ren

    2008-11-01

    A novel bis-β-diketone organic ligand, 1,1'-(2,6-bispyridyl)bis-3-( p-methoxyphenyl)-1,3-propanedione (L 1) and its derivatives, a novel bispyrazole ligand, 2,6-bis(5-(4-methoxyphenyl)-1H-pyrazol-3-yl)pyridine (L 2) were designed and synthesized and their complexes with Tb(III) ion were successfully prepared. The ligands and the corresponding metal complexes were characterized by elemental analysis, infrared, proton nuclear magnetic resonance spectroscopy and TG-DTA. Analysis of the IR spectra suggested that the lanthanide metal ion Tb(III) coordinated to the ligands via the nitrogen atom of the pyridine ring and the carbonyl oxygen atoms for ligand L 1 and the nitrogen atom of the pyrazole ring for ligand L 2. The fluorescence properties of the two complexes in solid state were investigated and it was discovered that the Tb(III) ions could be sensitized by both the ligand (L 1) and ligand (L 2) to some extent. In particular, the complex of ligand (L 2) is a better green luminescent material that could be used as a candidate material in organic light-emitting devices (OLEDs) since it could be much better sensitized by the ligand (L 2), and the fluorescence intensity of Tb(III) complex of L 2 are almost as twice strong as L 1's.

  5. Synthesis and ligand-based reduction chemistry of boron difluoride complexes with redox-active formazanate ligands

    NARCIS (Netherlands)

    Chang, M. -C.; Otten, E.

    2014-01-01

    Mono(formazanate) boron difluoride complexes (LBF2), which show remarkably facile and reversible ligand-based redox-chemistry, were synthesized by transmetallation of bis(formazanate) zinc complexes with boron trifluoride. The one-electron reduction product [LBF2](-)[Cp2Co](+) and a key intermediate

  6. Alkali metal salts of formazanate ligands : diverse coordination modes as a result of the nitrogen-rich [NNCNN] ligand backbone

    NARCIS (Netherlands)

    Travieso-Puente, Raquel; Chang, Mu-Chieh; Otten, Edwin

    2014-01-01

    Alkali metal salts of redox-active formazanate ligands were prepared, and their structures in the solid-state and in solution are determined. The nitrogen-rich [NNCNN] backbone of formazanates results in a varied coordination chemistry, with both the internal and terminal nitrogen atoms available fo

  7. Notch Ligand Endocytosis Generates Mechanical Pulling Force Dependent on Dynamin, Epsins and Actin

    Science.gov (United States)

    Meloty-Kapella, Laurence; Shergill, Bhupinder; Kuon, Jane; Botvinick, Elliot; Weinmaster, Gerry

    2012-01-01

    SUMMARY Notch signaling induced by cell surface ligands is critical to development and maintenance of many eukaryotic organisms. Notch and its ligands are integral membrane proteins that facilitate direct cell-cell interactions to activate Notch proteolysis and release the intracellular domain that directs Notch-specific cellular responses. Genetic studies suggest Notch ligands require endocytosis, ubiquitylation and epsin endocytic adaptors to activate signaling, yet the exact role ligand endocytosis serves remains unresolved. Here we characterize a molecularly distinct mode of clathrin-mediated endocytosis requiring ligand ubiquitylation, epsins and actin for ligand cells to activate signaling in Notch cells. Using a cell-bead optical tweezers system, we obtained evidence for cell-mediated mechanical force dependent on this distinct mode of ligand endocytosis. We propose mechanical pulling force produced by endocytosis of Notch-bound ligand drives conformational changes in Notch that permit activating proteolysis. PMID:22658936

  8. Deprotonation of C-alkyl groups of cationic N-heterocyclic ligands.

    Science.gov (United States)

    Cabeza, Javier A; García-Álvarez, Pablo; Pérez-Carreño, Enrique; Pruneda, Vanessa

    2012-04-21

    The C-alkyl groups of C-alkylpyrazinium-derived ligands have been selectively deprotonated by K[N(SiMe(3))(2)], through charge-controlled processes, to give neutral products that contain C-alkylidenepyrazine-derived ligands.

  9. 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....

  10. Switching of bacterial adhesion to a glycosylated surface by reversible reorientation of the carbohydrate ligand

    DEFF Research Database (Denmark)

    Weber, Theresa; Chrasekaran, Vijayan; Stamer, Insa

    2014-01-01

    The surface recognition in many biological systems is guided by the interaction of carbohydrate-specific proteins (lectins) with carbohydrate epitopes (ligands) located within the unordered glycoconjugate layer (glycocalyx) of cells. Thus, for recognition, the respective ligand has to reorient...

  11. KLIFS: a knowledge-based structural database to navigate kinase-ligand interaction space.

    Science.gov (United States)

    van Linden, Oscar P J; Kooistra, Albert J; Leurs, Rob; de Esch, Iwan J P; de Graaf, Chris

    2014-01-23

    Protein kinases regulate the majority of signal transduction pathways in cells and have become important targets for the development of designer drugs. We present a systematic analysis of kinase-ligand interactions in all regions of the catalytic cleft of all 1252 human kinase-ligand cocrystal structures present in the Protein Data Bank (PDB). The kinase-ligand interaction fingerprints and structure database (KLIFS) contains a consistent alignment of 85 kinase ligand binding site residues that enables the identification of family specific interaction features and classification of ligands according to their binding modes. We illustrate how systematic mining of kinase-ligand interaction space gives new insights into how conserved and selective kinase interaction hot spots can accommodate the large diversity of chemical scaffolds in kinase ligands. These analyses lead to an improved understanding of the structural requirements of kinase binding that will be useful in ligand discovery and design studies.

  12. 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

  13. Shaping the cavity of the macrocyclic ligand in metallocalix[4]arenes: the role of the ligand sphere.

    Science.gov (United States)

    Radius, U

    2001-12-17

    The coordination form of calix[4]arene ligands and therefore the cavity of the macrocyclic ligand can be controlled by other ligands in transition metal calix[4]arene complexes, if strong directing coligands such as oxo groups are used. This paper describes the synthesis and characterization of the d(0) transition metal complexes [Cax(OMe)(2)O(2)TiCl(2)] 1 (monoclinic, space group P2(1)/c, lattice constants a = 21.639(4), b = 20.152(3), c = 12.750(3) A, beta = 95.68(3), V = 5532.6(19) A(3)) and [Cax(OMe)(2)O(2)MoO(2)] 2 (monoclinic, space group P2/c, lattice constants a = 12.433(3), b = 16.348(3), c = 24.774(5) A, beta = 99.15(3), V = 4971.6(17) A(3)). Whereas in 1 the calix[4]arene ligand adopts an elliptically distorted cone conformation, the macrocyclic ligand binds in a paco-like conformation to the metal center of 2, in the solid state and in solution. This was predicted by density functional theory calculations on models of different isomers of 1 and 2: cis,cone-1',2', trans,cone-1',2', and cis,paco-1',2'. According to these calculations, the energetic difference of 72.9 kJ/mol between both cis-dioxomolybdenum compounds is quite pronounced in favor of the cis,paco isomer, and 28.0 kJ/mol for the titanium compounds in favor of the cis,cone isomer.

  14. Synthesis, Characterization and Antibacterial Activity of New Ln( Ⅲ) Complexes with an Unsymmetrical Schiff Base Ligand

    Institute of Scientific and Technical Information of China (English)

    BI Caifeng; YAN Liangliang; FAN Yuhua; ZHANG Xia; WANG Aidong

    2006-01-01

    A new unsymmetrical Schiff base ligand (H2LLi) was synthesized using L-lysine, salicylaldehyde and 2-hydroxyprepared and characterized by elemental analyses, IR spectra, UV spectra, TG-DTG and molar conductance.The antibacterial activities of the ligand and its complexes are also studied.The antibacterial experiments indicate that the ligand and its complexes possess antibacterial activity against Escherichia coli, Staphylococcus aureus and Bacillus subtilis and that the complexes have higher activity than those of the ligand.

  15. PDB ligand conformational energies calculated quantum-mechanically.

    Science.gov (United States)

    Sitzmann, Markus; Weidlich, Iwona E; Filippov, Igor V; Liao, Chenzhong; Peach, Megan L; Ihlenfeldt, Wolf-Dietrich; Karki, Rajeshri G; Borodina, Yulia V; Cachau, Raul E; Nicklaus, Marc C

    2012-03-26

    We present here a greatly updated version of an earlier study on the conformational energies of protein-ligand complexes in the Protein Data Bank (PDB) [Nicklaus et al. Bioorg. Med. Chem. 1995, 3, 411-428], with the goal of improving on all possible aspects such as number and selection of ligand instances, energy calculations performed, and additional analyses conducted. Starting from about 357,000 ligand instances deposited in the 2008 version of the Ligand Expo database of the experimental 3D coordinates of all small-molecule instances in the PDB, we created a "high-quality" subset of ligand instances by various filtering steps including application of crystallographic quality criteria and structural unambiguousness. Submission of 640 Gaussian 03 jobs yielded a set of about 415 successfully concluded runs. We used a stepwise optimization of internal degrees of freedom at the DFT level of theory with the B3LYP/6-31G(d) basis set and a single-point energy calculation at B3LYP/6-311++G(3df,2p) after each round of (partial) optimization to separate energy changes due to bond length stretches vs bond angle changes vs torsion changes. Even for the most "conservative" choice of all the possible conformational energies-the energy difference between the conformation in which all internal degrees of freedom except torsions have been optimized and the fully optimized conformer-significant energy values were found. The range of 0 to ~25 kcal/mol was populated quite evenly and independently of the crystallographic resolution. A smaller number of "outliers" of yet higher energies were seen only at resolutions above 1.3 Å. The energies showed some correlation with molecular size and flexibility but not with crystallographic quality metrics such as the Cruickshank diffraction-component precision index (DPI) and R(free)-R, or with the ligand instance-specific metrics such as occupancy-weighted B-factor (OWAB), real-space R factor (RSR), and real-space correlation coefficient

  16. Understanding ligand effects in gold clusters using mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Grant E.; Laskin, Julia

    2016-01-01

    This review summarizes recent research on the influence of phosphine ligands on the size, stability, and reactivity of gold clusters synthesized in solution. Sub-nanometer clusters exhibit size- and composition-dependent properties that are unique from those of larger nanoparticles. The highly tunable properties of clusters and their high surface-to-volume ratio make them promising candidates for a variety of technological applications. However, because “each-atom-counts” toward defining cluster properties it is critically important to develop robust synthesis methods to efficiently prepare clusters of predetermined size. For decades phosphines have been known to direct the size-selected synthesis of gold clusters. Despite the preparation of numerous species it is still not understood how different functional groups at phosphine centers affect the size and properties of gold clusters. Using electrospray ionization mass spectrometry (ESI-MS) it is possible to characterize the effect of ligand substitution on the distribution of clusters formed in solution at defined reaction conditions. In addition, ligand exchange reactions on preformed clusters may be monitored using ESI-MS. Collision induced dissociation (CID) may also be employed to obtain qualitative insight into the fragmentation of mixed ligand clusters and the relative binding energies of differently substituted phosphines. Quantitative ligand binding energies and cluster stability may be determined employing surface induced dissociation (SID) in a custom-built Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR-MS). Rice-Ramsperger-Kassel-Marcus (RRKM) based modeling of the SID data allows dissociation energies and entropy values to be extracted that may be compared with the results of high-level theoretical calculations. The charge reduction and reactivity of atomically precise gold clusters, including partially ligated species generated in the gas-phase by in source CID, on well

  17. Understanding ligand effects in gold clusters using mass spectrometry.

    Science.gov (United States)

    Johnson, Grant E; Laskin, Julia

    2016-06-21

    This review summarizes recent research on the influence of phosphine ligands on the size, stability, and reactivity of gold clusters synthesized in solution. Sub-nanometer clusters exhibit size- and composition-dependent properties that are unique from those of larger nanoparticles. The highly tunable properties of clusters and their high surface-to-volume ratio make them promising candidates for a variety of technological applications. However, because "each-atom-counts" toward defining cluster properties it is critically important to develop robust synthesis methods to efficiently prepare clusters of predetermined size. For decades phosphines have been known to direct the size-selected synthesis of gold clusters. Despite the preparation of numerous species it is still not understood how different functional groups at phosphine centers affect the size and properties of gold clusters. Using electrospray ionization mass spectrometry (ESI-MS) it is possible to characterize the effect of ligand substitution on the distribution of clusters formed in solution at defined reaction conditions. In addition, ligand exchange reactions on preformed clusters may be monitored using ESI-MS. Collision induced dissociation (CID) may also be employed to obtain qualitative insight into the fragmentation of mixed ligand clusters and the relative binding energies of differently substituted phosphines. Quantitative ligand binding energies and cluster stability may be determined employing surface induced dissociation (SID) in a custom-built Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR-MS). Rice-Ramsperger-Kassel-Marcus (RRKM) based modeling of the SID data allows dissociation energies and entropy values to be extracted. The charge reduction and reactivity of atomically precise gold clusters, including partially ligated species generated in the gas-phase by in source CID, on well-defined surfaces may be explored using ion soft landing (SL) in a custom

  18. Computational approaches to modeling receptor flexibility upon ligand binding: Application to interfacially activated enzymes

    DEFF Research Database (Denmark)

    Wade, R.C.; Sobolev, V.; Ortiz, A.R. .

    1998-01-01

    Receptors generally undergo conformational change upon ligand binding. We describe how fairly simple techniques may be used in docking and design studies to account for some of the changes in the conformations of proteins on ligand binding. Simulations of protein-ligand interactions that give a m...

  19. 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

  20. Comprehensive assessment of flexible-ligand docking algorithms: current effectiveness and challenges.

    Science.gov (United States)

    Huang, Sheng-You

    2017-03-14

    Protein-ligand docking has been playing an important role in modern drug discovery. To model drug-target binding in real systems, a number of flexible-ligand docking algorithms with different sampling strategies and scoring methods have been subsequently developed over the past three decades, while rigid-ligand docking is still being used because of its compelling computational efficiency. Here, a comprehensive assessment has been conducted to investigate the effectiveness of flexible-ligand docking versus rigid-ligand docking for three representative docking algorithms (global optimization, incremental construction and multi-conformer docking) in virtual screening and pose prediction on the Directory of Useful Decoys. It was found that overall flexible-ligand docking did not achieve a statistically significant improvement in enrichments over rigid-ligand docking in virtual screening, but all docking programs significantly improved the success rates when considering ligand flexibility in pose prediction. The worse effectiveness of flexible-ligand docking in virtual screening than in pose prediction suggests that the challenges of current docking algorithms exist in ranking more than docking, although the use of flexible-ligand docking in virtual screening was justified by its better effectiveness for more flexible ligand in virtual screening. Challenges for scoring, including internal energy, charge polarization, entropy and flexibility, were investigated and discussed. An empirical way was also proposed to consider loss of ligand conformational entropy for virtual screening. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Synthesis and Reactivity of Chiral, Wide-Bite-Angle, Hybrid Diphosphorus Ligands

    NARCIS (Netherlands)

    C.F. Czauderna; D.B. Cordes; A.M.Z. Slawin; C. Müller; J.I. van der Vlugt; D. Vogt; P.C.J. Kamer

    2014-01-01

    Effective and modular synthetic approaches toward phosphine-phosphite ligands and phosphine-phosphonite ligands featuring a diphenyl ether backbone have been developed. The phosphine-phosphite ligands are obtained by a two-step protocol from 2-bromo-2-methoxydiphenyl ether. The phosphine-phosphonite

  2. Internalization mechanisms of the epidermal growth factor receptor after activation with different ligands

    DEFF Research Database (Denmark)

    Henriksen, Lasse; Grandal, Michael Vibo; Knudsen, Stine Louise Jeppe

    2013-01-01

    fully inhibits EGFR degradation after all ligands tested. Furthermore, inhibition of dynamin function blocked EGFR internalization after stimulation with all ligands. Knocking out a number of clathrin-independent dynamin-dependent pathways of internalization had no effect on the ligand...

  3. Influence of bulky yet flexible N-heterocyclic carbene ligands in gold catalysis.

    Science.gov (United States)

    Collado, Alba; Patrick, Scott R; Gasperini, Danila; Meiries, Sebastien; Nolan, Steven P

    2015-01-01

    Three new Au(I) complexes of the formula [Au(NHC)(NTf2)] (NHC = N-heterocyclic carbene) bearing bulky and flexible ligands have been synthesised. The ligands studied are IPent, IHept and INon which belong to the 'ITent' ('Tent' for 'tentacular') family of NHC derivatives. The effect of these ligands in gold-promoted transformations has been investigated.

  4. Olefin Metathesis Mediated By: - Schiff Base Ru-Alkylidenes -Ru-Alkylidenes Bearing Unsymmetrical NH Ligands

    Science.gov (United States)

    Monsaert, Stijn; Voort, Pascal Van Der; Ledoux, Nele; Allaert, Bart; Drozdzak, Renata; Verpoort, Francis

    The classic Grubbs second-generation complex 2 was modified through 1. The introduction of a bidentate Schiff base ligand 2. Changes in the amino side groups of the NHC ligand Representative olefin metathesis test reactions show the effects induced by the ligand modifications and demonstrate some interesting new properties of the described catalysts. catalysts.

  5. Amino acids as chiral anionic ligands for ruthenium based asymmetric olefin metathesis.

    Science.gov (United States)

    Ivry, Elisa; Ben-Asuly, Amos; Goldberg, Israel; Lemcoff, N Gabriel

    2015-03-01

    Several amino acid ligands were introduced into the Hoveyda-Grubbs 2nd generation complex by a facile anionic ligand exchange. The chiral pre-catalysts obtained displayed enantioselectivity in asymmetric ring-closing and ring-opening cross-metathesis reactions. Reduction of the lability of the carboxylate ligands was found to be cardinal for improving the observed enantiomeric product enrichment.

  6. Gut microbiota regulates NKG2D ligand expression on intestinal epithelial cells

    DEFF Research Database (Denmark)

    Hansen, Camilla Hartmann Friis; Holm, Thomas L.; Krych, Lukasz

    2013-01-01

    Intestinal epithelial cells (IECs) are one of a few cell types in the body with constitutive surface expression of natural killer group 2 member D (NKG2D) ligands, although the magnitude of ligand expression by IECs varies. Here, we investigated whether the gut microbiota regulates the NKG2D ligand...

  7. Silver, Gold, Palladium Nanoparticles: Ligand Design, Synthesis and Polymer Composites

    Science.gov (United States)

    Iqbal, Muhammad

    Metal nanoparticles, especially gold nanoparticles (AuNPs), have been extensively studied due to their interesting optical properties and potential applications in emerging technologies like drug delivery, cancer therapy, catalysis, chemical and bio-sensing and microelectronics devices. Alkyl thiol ligands in the form of self assembled monolayers are often used to stabilize and functionalize the gold nanoparticles while other types of ligands have been rarely employed and the properties of AuNPs protected by different types of ligands have not been studied comprehensively and comparatively. This dissertation reports the first comparative studies on the thermal and chemical stability of AuNPs protected by alkyl thiolates, alkyl selenolates, dialkyl dithiophosphinates, and dialkyl dithiophosphates (Chapters 2 and 3). AuNPs protected by dialkyl dithiophosphinates and dialkyl dithiophosphates are unprecedented. All AuNPs were prepared from amine protected precursor AuNPs by ligand exchange to ensure similar size, size distribution, and chemical composition. They were extensively characterized by solution 1H-NMR and UV-VIS spectroscopy, transmission electron microscopy (TEM), thermal analysis, X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) analysis. For the first time, thermal stability was investigated by differential scanning calorimetry (DSC) that provided more accurate decomposition temperatures and enthalpies, whereas chemical stability was tested as the availability of the gold surface towards etching with cyanide in different solvents. Surprisingly, alkyl selenolate protected AuNPs are thermally less stable than alkyl thiolate protected AuNPs despite their proposed stronger binding to the gold surface and a much more crystalline monolayer, which suggests that different decomposition mechanisms apply to alkyl thiolate and alkyl selenolate protected AuNPs. Dialkyl dithiophosphinates and dialkyl dithiophosphates protected AuNPs are thermally

  8. Highly selective ligand binding by Methylophilus methylotrophus cytochrome c''.

    Science.gov (United States)

    Quintas, Pedro O; Catarino, Teresa; Todorovic, Smilja; Turner, David L

    2011-06-28

    Cytochrome c'' (cyt c'') from Methylophilus methylotrophus is unusual insofar as the heme has two axial histidine ligands in the oxidized form but one is detached when the protein is reduced. Despite cyt c'' having an axial site available for binding small ligands, we show here that only NO binds readily to the ferrous cyt c''. Binding of CO, as well as CN(-), on the other hand requires considerable structural reorganization, or reduction of the disulfide bridge close to the heme. Standard free energies for the binding of NO and CO reveal high selectivity of the ferrous cyt c'' for NO, indicating its putative physiological role. In this work, we characterize in detail the kinetics of NO binding and the structural features of the Fe(2+)-NO adduct by stopped-flow and resonance Raman spectroscopy, respectively.

  9. Isothermal Titration Calorimetry for Measuring Macromolecule-Ligand Affinity

    Science.gov (United States)

    Duff,, Michael R.; Grubbs, Jordan; Howell, Elizabeth E.

    2011-01-01

    Isothermal titration calorimetry (ITC) is a useful tool for understanding the complete thermodynamic picture of a binding reaction. In biological sciences, macromolecular interactions are essential in understanding the machinery of the cell. Experimental conditions, such as buffer and temperature, can be tailored to the particular binding system being studied. However, careful planning is needed since certain ligand and macromolecule concentration ranges are necessary to obtain useful data. Concentrations of the macromolecule and ligand need to be accurately determined for reliable results. Care also needs to be taken when preparing the samples as impurities can significantly affect the experiment. When ITC experiments, along with controls, are performed properly, useful binding information, such as the stoichiometry, affinity and enthalpy, are obtained. By running additional experiments under different buffer or temperature conditions, more detailed information can be obtained about the system. A protocol for the basic setup of an ITC experiment is given. PMID:21931288

  10. 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.

  11. Structural Dynamics of the Cereblon Ligand Binding Domain

    Science.gov (United States)

    Hartmann, Marcus D.; Boichenko, Iuliia; Coles, Murray; Lupas, Andrei N.; Hernandez Alvarez, Birte

    2015-01-01

    Cereblon, a primary target of thalidomide and its derivatives, has been characterized structurally from both bacteria and animals. Especially well studied is the thalidomide binding domain, CULT, which shows an invariable structure across different organisms and in complex with different ligands. Here, based on a series of crystal structures of a bacterial representative, we reveal the conformational flexibility and structural dynamics of this domain. In particular, we follow the unfolding of large fractions of the domain upon release of thalidomide in the crystalline state. Our results imply that a third of the domain, including the thalidomide binding pocket, only folds upon ligand binding. We further characterize the structural effect of the C-terminal truncation resulting from the mental-retardation linked R419X nonsense mutation in vitro and offer a mechanistic hypothesis for its irresponsiveness to thalidomide. At 1.2Å resolution, our data provide a view of thalidomide binding at atomic resolution. PMID:26024445

  12. Structural dynamics of the cereblon ligand binding domain.

    Directory of Open Access Journals (Sweden)

    Marcus D Hartmann

    Full Text Available Cereblon, a primary target of thalidomide and its derivatives, has been characterized structurally from both bacteria and animals. Especially well studied is the thalidomide binding domain, CULT, which shows an invariable structure across different organisms and in complex with different ligands. Here, based on a series of crystal structures of a bacterial representative, we reveal the conformational flexibility and structural dynamics of this domain. In particular, we follow the unfolding of large fractions of the domain upon release of thalidomide in the crystalline state. Our results imply that a third of the domain, including the thalidomide binding pocket, only folds upon ligand binding. We further characterize the structural effect of the C-terminal truncation resulting from the mental-retardation linked R419X nonsense mutation in vitro and offer a mechanistic hypothesis for its irresponsiveness to thalidomide. At 1.2Å resolution, our data provide a view of thalidomide binding at atomic resolution.

  13. Modeling regionalized volumetric differences in protein-ligand binding cavities.

    Science.gov (United States)

    Chen, Brian Y; Bandyopadhyay, Soutir

    2012-06-21

    Identifying elements of protein structures that create differences in protein-ligand binding specificity is an essential method for explaining the molecular mechanisms underlying preferential binding. In some cases, influential mechanisms can be visually identified by experts in structural biology, but subtler mechanisms, whose significance may only be apparent from the analysis of many structures, are harder to find. To assist this process, we present a geometric algorithm and two statistical models for identifying significant structural differences in protein-ligand binding cavities. We demonstrate these methods in an analysis of sequentially nonredundant structural representatives of the canonical serine proteases and the enolase superfamily. Here, we observed that statistically significant structural variations identified experimentally established determinants of specificity. We also observed that an analysis of individual regions inside cavities can reveal areas where small differences in shape can correspond to differences in specificity.

  14. Multitopic ligand design: a concept for single-source precursors.

    Science.gov (United States)

    Gschwind, Fabienne; Sereda, Olha; Fromm, Katharina M

    2009-11-16

    The multitopic ligand O,O'-bisnicotinic acid tetraethylene glycol, L, was designed for the coordination of two distinct types of metal ions. In this work, we describe how the O-donor part of L is used to coordinate to alkaline earth metal ions and that the N-donor atoms of L bind to group 11 elements. This makes L a suitable ligand for the combination of both metal ion types within the same compound. This concept will be exemplified by highlighting the pure Ca(2+) complexes, a Cu(+)-coordination polymer network, as well as the mixed-metal compound, which can be used as a single-source precursor for mixed-metal oxide materials.

  15. Genetics, genomics, and evolutionary biology of NKG2D ligands.

    Science.gov (United States)

    Carapito, Raphael; Bahram, Seiamak

    2015-09-01

    Human and mouse NKG2D ligands (NKG2DLs) are absent or only poorly expressed by most normal cells but are upregulated by cell stress, hence, alerting the immune system in case of malignancy or infection. Although these ligands are numerous and highly variable (at genetic, genomic, structural, and biochemical levels), they all belong to the major histocompatibility complex class I gene superfamily and bind to a single, invariant, receptor: NKG2D. NKG2D (CD314) is an activating receptor expressed on NK cells and subsets of T cells that have a key role in the recognition and lysis of infected and tumor cells. Here, we review the molecular diversity of NKG2DLs, discuss the increasing appreciation of their roles in a variety of medical conditions, and propose several explanations for the evolutionary force(s) that seem to drive the multiplicity and diversity of NKG2DLs while maintaining their interaction with a single invariant receptor.

  16. SOME COMPLEXES OF Ni(II CONTAINING MIXES LIGANDS

    Directory of Open Access Journals (Sweden)

    Z.F DAWOOD

    2004-06-01

    Full Text Available Nickel (II Complexes containing mixed ligands : semicarbazone (benzaldehyde semicarbazone-BSCH; 2-fluorobenzaldehyde semicarbazone-FSCH and substituted pyridine {2-aminopyridine (p1 ; 4-aminopyridine (p2 ; 2,3-dicarboxypyridine (p3 ; 2-amino-3-hydroxypyridine (p4 ; 2-amino-4-methyl-pyridine (p5 and 3,4-dicarboxypyridine (p6 have been prepared. The resulted complexes have been characterized by elemental analysis, molar conductance values, magnetic moment, infrared and electronic spectral data. Complexes of the type [Ni2(SCH2(P4(NO32](NO32 and [Ni2(SCH2(P4(NO33]NO3 (where SCH= BSCH or FSCH, P= substituted pyridine ligands have been proposed.

  17. 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.

  18. Inside job: ligand-receptor pharmacology beneath the plasma membrane.

    Science.gov (United States)

    Babcock, Joseph J; Li, Min

    2013-07-01

    Most drugs acting on the cell surface receptors are membrane permeable and thus able to engage their target proteins in different subcellular compartments. However, these drugs' effects on cell surface receptors have historically been studied on the plasma membrane alone. Increasing evidence suggests that small molecules may also modulate their targeted receptors through membrane trafficking or organelle-localized signaling inside the cell. These additional modes of interaction have been reported for functionally diverse ligands of GPCRs, ion channels, and transporters. Such intracellular drug-target engagements affect cell surface expression. Concurrent intracellular and cell surface signaling may also increase the complexity and therapeutic opportunities of small molecule modulation. Here we discuss examples of ligand-receptor interactions that are present in both intra- and extracellular sites, and the potential therapeutic opportunities presented by this phenomenon.

  19. Light-induced regulation of ligand-gated channel activity.

    Science.gov (United States)

    Bregestovski, Piotr; Maleeva, Galyna; Gorostiza, Pau

    2017-08-31

    The control of ligand-gated receptors with light using photochromic compounds has evolved from the first handcrafted examples to accurate, engineered receptors, whose development is supported by rational design, high-resolution protein structures, comparative pharmacology and molecular biology manipulations. Photoswitchable regulators have been designed and characterized for a large number of ligand-gated receptors in the mammalian nervous system, including nicotinic acetylcholine, glutamate and GABA receptors. They provide a well-equipped toolbox to investigate synaptic and neuronal circuits in all-optical experiments. This focused review discusses the design and properties of these photoswitches, their applications and shortcomings and future perspectives in the field. © 2017 The British Pharmacological Society.

  20. Rational design of a triple helix-specific intercalating ligand.

    Science.gov (United States)

    Escudé, C; Nguyen, C H; Kukreti, S; Janin, Y; Sun, J S; Bisagni, E; Garestier, T; Hélène, C

    1998-03-31

    DNA triple helices offer new perspectives toward oligonucleotide-directed gene regulation. However, the poor stability of some of these structures might limit their use under physiological conditions. Specific ligands can intercalate into DNA triple helices and stabilize them. Molecular modeling and thermal denaturation experiments suggest that benzo[f]pyrido[3, 4-b]quinoxaline derivatives intercalate into triple helices by stacking preferentially with the Hoogsteen-paired bases. Based on this model, it was predicted that a benzo[f]quino[3,4-b]quinoxaline derivative, which possesses an additional aromatic ring, could engage additional stacking interactions with the pyrimidine strand of the Watson-Crick double helix upon binding of this pentacyclic ligand to a triplex structure. This compound was synthesized. Thermal denaturation experiments and inhibition of restriction enzyme cleavage show that this new compound can indeed stabilize triple helices with great efficiency and specificity and/or induce triple helix formation under physiological conditions.

  1. Photomechanical actuation of ligand geometry in enantioselective catalysis.

    Science.gov (United States)

    Kean, Zachary S; Akbulatov, Sergey; Tian, Yancong; Widenhoefer, Ross A; Boulatov, Roman; Craig, Stephen L

    2014-12-22

    A catalyst that couples a photoswitch to the biaryl backbone of a chiral bis(phosphine) ligand, thus allowing photochemical manipulation of ligand geometry without perturbing the electronic structure is reported. The changes in catalyst activity and selectivity upon switching can be attributed to intramolecular mechanical forces, thus laying the foundation for a new class of catalysts whose selectivity can be varied smoothly and in situ over a useful range by controlling molecular stress experienced by the catalyst during turnover. Forces on the order of 100 pN are generated, thus leading to measurable changes in the enantioselectivities of asymmetric Heck arylations and Trost allylic alkylations. The differential coupling between applied force and competing stereochemical pathways is quantified and found to be more efficient for the Heck arylations.

  2. Topological Analyses of Protein-Ligand Binding: a Network Approach.

    Science.gov (United States)

    Costanzi, Stefano

    2016-01-01

    Proteins can be conveniently represented as networks of interacting residues, thus allowing the study of several network parameters that can shed light onto several of their structural and functional aspects. With respect to the binding of ligands, which are central for the function of many proteins, network analysis may constitute a possible route to assist the identification of binding sites. As the bulk of this review illustrates, this has generally been easier for enzymes than for non-enzyme proteins, perhaps due to the different topological nature of the binding sites of the former over those of the latter. The article also illustrates how network representations of binding sites can be used to search PDB structures in order to identify proteins that bind similar molecules and, lastly, how codifying proteins as networks can assist the analysis of the conformational changes consequent to ligand binding.

  3. Inside job: ligand-receptor pharmacology beneath the plasma membrane

    Institute of Scientific and Technical Information of China (English)

    Joseph J BABCOCK; Min LI

    2013-01-01

    Most drugs acting on the cell surface receptors are membrane permeable and thus able to engage their target proteins in different subcellular compartments.However,these drugs' effects on cell surface receptors have historically been studied on the plasma membrane alone.Increasing evidence suggests that small molecules may also modulate their targeted receptors through membrane trafficking or organelle-localized signaling inside the cell.These additional modes of interaction have been reported for functionally diverse ligands of GPCRs,ion channels,and transporters.Such intracellular drug-target engagements affect cell surface expression.Concurrent intracellular and cell surface signaling may also increase the complexity and therapeutic opportunities of small molecule modulation.Here we discuss examples of ligand-receptor interactions that are present in both intra- and extracellular sites,and the potential therapeutic opportunities presented by this phenomenon.

  4. A Structural Switch between Agonist and Antagonist Bound Conformations for a Ligand-Optimized Model of the Human Aryl Hydrocarbon Receptor Ligand Binding Domain

    Directory of Open Access Journals (Sweden)

    Arden Perkins

    2014-10-01

    Full Text Available The aryl hydrocarbon receptor (AHR is a ligand-activated transcription factor that regulates the expression of a diverse group of genes. Exogenous AHR ligands include the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, which is a potent agonist, and the synthetic AHR antagonist N-2-(1H-indol-3ylethyl-9-isopropyl-2- (5-methylpyridin-3-yl-9H-purin-6-amine (GNF351. As no experimentally determined structure of the ligand binding domain exists, homology models have been utilized for virtual ligand screening (VLS to search for novel ligands. Here, we have developed an “agonist-optimized” homology model of the human AHR ligand binding domain, and this model aided in the discovery of two human AHR agonists by VLS. In addition, we performed molecular dynamics simulations of an agonist TCDD-bound and antagonist GNF351-bound version of this model in order to gain insights into the mechanics of the AHR ligand-binding pocket. These simulations identified residues 307–329 as a flexible segment of the AHR ligand pocket that adopts discrete conformations upon agonist or antagonist binding. This flexible segment of the AHR may act as a structural switch that determines the agonist or antagonist activity of a given AHR ligand.

  5. Age dependent accumulation patterns of advanced glycation end product receptor (RAGE) ligands and binding intensities between RAGE and its ligands differ in the liver, kidney, and skeletal muscle.

    Science.gov (United States)

    Son, Myeongjoo; Chung, Wook-Jin; Oh, Seyeon; Ahn, Hyosang; Choi, Chang Hu; Hong, Suntaek; Park, Kook Yang; Son, Kuk Hui; Byun, Kyunghee

    2017-01-01

    Much evidence indicates receptor for advanced glycation end products (RAGE) related inflammation play essential roles during aging. However, the majority of studies have focused on advanced glycation end products (AGEs) and not on other RAGE ligands. In the present study, the authors evaluated whether the accumulation of RAGE ligands and binding intensities between RAGE and its ligands differ in kidney, liver, and skeletal muscle during aging. In C57BL/6 N mice aged 12 weeks, 12 months, and 22 months, ligands accumulation, binding intensities between RAGE and its ligands, activated macrophage infiltration, M1/M2 macrophage expression, glyoxalase-1expression, and signal pathways related to inflammation were evaluated. The RAGE ligands age-associated accumulation patterns were found to be organ dependent. Binding intensities between RAGE and its ligands in kidney and liver increased with age, but those in skeletal muscle were unchanged. Infiltration of activated macrophages in kidney and liver increased with age, but infiltration in the skeletal muscle was unchanged. M1 expression increased and M2 and glyoxalase-1 expression decreased with age in kidney and liver, but their expressions in skeletal muscle were not changed. These findings indicate patterns of RAGE ligands accumulation, RAGE/ligands binding intensities, or inflammation markers changes during aging are organs dependent.

  6. Analyzing protein-ligand interactions by dynamic NMR spectroscopy.

    Science.gov (United States)

    Mittermaier, Anthony; Meneses, Erick

    2013-01-01

    Nuclear magnetic resonance (NMR) spectroscopy can provide detailed information on protein-ligand interactions that is inaccessible using other biophysical techniques. This chapter focuses on NMR-based approaches for extracting affinity and rate constants for weakly binding transient protein complexes with lifetimes of less than about a second. Several pulse sequences and analytical techniques are discussed, including line-shape simulations, spin-echo relaxation dispersion methods (CPMG), and magnetization exchange (EXSY) experiments.

  7. Aerobic oxidation assisted by ligand-free palladium catalysts

    Institute of Scientific and Technical Information of China (English)

    Jia Rui Wang; Chu Ting Yang; Lei Liu; Qing Xiang Guo

    2007-01-01

    Aerobic oxidation of electron-rich benzylic and phenyl allylic alcohols was achieved with high yields with only 0.1 mol.% ofPd(OAc)2 catalyst in the absence of any ligand. This procedure was expected to be valuable for realistic industrial-scale applications from both economic as well as environmental points of view.(C) 2006 Qing Xiang Guo. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  8. Synthesis and vibrational study of some polydentate ligands

    Science.gov (United States)

    Esteban, M. F. Gargallo; Serrano, R. Vilaplana; Vilchez, F. González

    Sodium salts of iminodiacetic acid (IDA), ethylenediaminetetraacetic acid (EDTA), 1,2-propylenediaminetetraacetic acid (PDTA) and 1,2-diaminocyclohexanetetraacetic acid (DCTA) were prepared by modification of the literature methods and their i.r. and Raman spectra were studied. The results obtained by application of both techniques allowed a better characterization of these polydentate ligands. Raman spectroscopy was specially useful in elucidating structural aspects in compounds containing acetate groups.

  9. Supervised Machine Learning Methods Applied to Predict Ligand- Binding Affinity.

    Science.gov (United States)

    Heck, Gabriela S; Pintro, Val O; Pereira, Richard R; de Ávila, Mauricio B; Levin, Nayara M B; de Azevedo, Walter F

    2017-01-01

    Calculation of ligand-binding affinity is an open problem in computational medicinal chemistry. The ability to computationally predict affinities has a beneficial impact in the early stages of drug development, since it allows a mathematical model to assess protein-ligand interactions. Due to the availability of structural and binding information, machine learning methods have been applied to generate scoring functions with good predictive power. Our goal here is to review recent developments in the application of machine learning methods to predict ligand-binding affinity. We focus our review on the application of computational methods to predict binding affinity for protein targets. In addition, we also describe the major available databases for experimental binding constants and protein structures. Furthermore, we explain the most successful methods to evaluate the predictive power of scoring functions. Association of structural information with ligand-binding affinity makes it possible to generate scoring functions targeted to a specific biological system. Through regression analysis, this data can be used as a base to generate mathematical models to predict ligandbinding affinities, such as inhibition constant, dissociation constant and binding energy. Experimental biophysical techniques were able to determine the structures of over 120,000 macromolecules. Considering also the evolution of binding affinity information, we may say that we have a promising scenario for development of scoring functions, making use of machine learning techniques. Recent developments in this area indicate that building scoring functions targeted to the biological systems of interest shows superior predictive performance, when compared with other approaches. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. A statistical mechanics handbook for protein-ligand binding simulation.

    Science.gov (United States)

    Rocchia, Walter; Bonella, Sara

    2013-01-01

    In this work, the fundamental elements of statistical mechanics underlying the simulation of the protein-ligand binding process, such as statistical ensembles and the concept of microscopic estimators of macroscopic observables and free energy, are summarized in a self consistent fashion. Particular attention is then devoted to the introduction of some mathematical tools that are used in atomistic simulations aimed at estimating binding affinities and free energy profiles, and to the illustration of the origins of the difficulties encountered in this endeavor.

  11. Zwitterionic Group VIII transition metal initiators supported by olefin ligands

    Science.gov (United States)

    Bazan, Guillermo C.; Chen, Yaofeng

    2011-10-25

    A zwitterionic Group VIII transition metal complex containing the simple and relatively small 3-(arylimino)-but-1-en-2-olato ligand that catalyzes the formation of polypropylene and high molecular weight polyethylene. A novel feature of this catalyst is that the active species is stabilized by a chelated olefin adduct. The present invention also provides methods of polymerizing olefin monomers using zwitterionic catalysts, particularly polypropylene and high molecular weight polyethylene.

  12. Chemoselective ligand patterning of electroactive surfaces using microfluidics.

    Science.gov (United States)

    Westcott, Nathan P; Yousaf, Muhammad N

    2009-10-01

    To generate model substrates for cell adhesion, we have developed two different biocompatible strategies based on self-assembled monolayers (SAMs) of alkanethiolates on gold terminated with latent ketones and aldehydes. Under spatial control, the hydroquinone and alcohol-terminated SAMs can be oxidized to allow for oxyamine ligand patterning on the surface with microfluidic cassettes. These immobilization strategies were characterized by electrochemistry, fluorescence, and utilizing a cell adhesive peptide, cell patterns were generated.

  13. Complexed nitrogen heterosuperbenzene : The coordinating properties of a remarkable ligand

    NARCIS (Netherlands)

    Draper, Sylvia M.; Gregg, Daniel J.; Schofield, Emma R.; Browne, Wesley R.; Duati, Marco; Vos, Johannes G.; Passaniti, Paolo

    2004-01-01

    Tetra-peri-(tert-butyl-benzo)-di-peri-(pyrimidino)-coronene 1, the parent compound of the nitrogen heterosuperbenzene family N-HSB, is employed as a novel monotopic ligand in the formation of [Pd(eta(3)-C3H5)(1)]PF6 2 and [Ru(bpy)(2)(1)](PF6)(2) (where bpy = 2,2'-bipyridine 3a and d(8)-2,2'-bipyridi

  14. Yttrium alkyl complexes with triamino-amide ligands

    NARCIS (Netherlands)

    Bambirra, Sergio; Boot, Steven J.; Leusen, Daan van; Meetsma, Auke; Hessen, Bart

    2004-01-01

    Two new monoanionic tetradentate triamino-amide ligands, [(Me2NCH2CH2)(2)N-B-N(t-Bu)](-) (B = (CH2)(2), L-1; SiMe2, L-2) were prepared. Reaction of LIH with Y(CH2SiMe3)(3)(THF)(2) yielded (LY)-Y-1(CH2SiMe3)(2) (1), which was structurally characterized. Compound 1 decomposes at ambient temperature vi

  15. Rational design of metal coordination compounds with azomethine ligands

    Energy Technology Data Exchange (ETDEWEB)

    Garnovskii, Alexander D; Vasil' chenko, Igor S [Institute of Physical and Organic Chemistry, Rostov State University, Rostov-on-Don (Russian Federation)

    2002-11-30

    This review surveys the state of art in the coordination chemistry of chelating azomethine systems, viz., amino(hydroxy)-azomethines, {beta}-aminovinyl ketones, {beta}-aminovinylimines and their sulfur- and selenium-containing analogues. Variations in the fine structure of azomethine ligands allow one to perform the targeted synthesis of chelate and molecular, mono-, bi- and polynuclear, homo- and heterometallic structures. The bibliography includes 425 reference000.

  16. 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.

  17. [Endorphines--the endogenous ligands of opiate receptors (author's transl)].

    Science.gov (United States)

    Teschemacher, H

    1978-01-01

    The demonstration of opiate receptors in the nervous tissue of vertebrates in 1973 was the starting point of an intensive search for the endogenous ligands of these receptors. During the following years, several of such "edogenous opiates", called "endorphines", were isolated from various tissues of the mammalian organism. These are peptides which are able to elicit the same effects as do opiates. Possibly, they play a role in the reaction of the organism to stress.

  18. Syntheses and crystal structures of two mixed-ligand dimeric zinc complexes containing a dithiol ligand and an open chain crown ether ligand with terminal quinolyl groups

    Science.gov (United States)

    Li, Cheng-Juan; Dou, Jian-Min; Li, Da-Cheng; Wang, Da-Qi

    2006-02-01

    Two mixed-ligand zinc complexes Zn(L)(H 2O)(mnt) ( 1) and Zn(L)(H 2O)(i-mnt) ( 2) (where L=2,6-bis(8'-quinoylyloxymethyl)pyridine, mnt =1,2-dicyanoethylene-1,2-ditholate and i-mnt =1,1-dicyanoethylene-2,2-ditholate) have been synthesized and characterized by elemental analysis, FT-IR spectra, and single-crystal X-ray diffraction. Complexes 1 and 2 both crystallize in the monoclinic system, space group C2/ c and each displays a distorted trigonal bipyramidal around zinc atom. The coordination sphere of Zn is NO 2S 2 type, where the dithiol ligand (mnt or i-mnt) and one terminal quinolyl group of L act as the chelate S, S and N, O donor sets, respectively, besides the coordination water molecules. Furthermore, there are intramolecular H-bonds occurred between the coordination water molecule and the N2, N3 atoms of the L and the molecules of 1 and 2 both form the dimers through the intermolecular π-π stacking interactions.

  19. 2 : 2 Fe(III): ligand and "adamantane core" 4 : 2 Fe(III): ligand (hydr)oxo complexes of an acyclic ditopic ligand

    DEFF Research Database (Denmark)

    Ghiladi, Morten; Larsen, Frank B.; McKenzie, Christine J.;

    2005-01-01

    A bis-hydroxo-bridged diiron(III) complex and a bis-mu-oxo-bis-mu-hydroxo-bridged tetrairon( III) complex are isolated from the reaction of 2,6-bis((N, N'-bis-(2-picolyl) amino) methyl)-4-tert-butylphenol (Hbpbp) with iron perchlorate in acidic and neutral solutions respectively. The X......-ray structure of the dinuclear complex [{( Hbpbp) Fe(mu-OH)}(2)](ClO4)(4) center dot 2C(3)H(6)O ( 1 center dot 2C(3)H(6)O) shows that only one of the metal-binding cavities of each ligand is occupied by an iron( III) atom and two [Fe(Hbpbp)](3+) units are linked together by two hydroxo bridging groups to form...... bond lengths of the two different octahedral iron sites: Fe -mu-OH, 1.953( 5), 2.013( 5) angstrom and Fe-mu-O, 1.803( 5), 1.802( 5) angstrom. The difference in ligand environment is too small for allowing Mossbauer spectroscopy to distinguish between the two crystallographically independent Fe sites...

  20. 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.

  1. Anaerobic biosynthesis of the lower ligand of vitamin B12.

    Science.gov (United States)

    Hazra, Amrita B; Han, Andrew W; Mehta, Angad P; Mok, Kenny C; Osadchiy, Vadim; Begley, Tadhg P; Taga, Michiko E

    2015-08-25

    Vitamin B12 (cobalamin) is required by humans and other organisms for diverse metabolic processes, although only a subset of prokaryotes is capable of synthesizing B12 and other cobamide cofactors. The complete aerobic and anaerobic pathways for the de novo biosynthesis of B12 are known, with the exception of the steps leading to the anaerobic biosynthesis of the lower ligand, 5,6-dimethylbenzimidazole (DMB). Here, we report the identification and characterization of the complete pathway for anaerobic DMB biosynthesis. This pathway, identified in the obligate anaerobic bacterium Eubacterium limosum, is composed of five previously uncharacterized genes, bzaABCDE, that together direct DMB production when expressed in anaerobically cultured Escherichia coli. Expression of different combinations of the bza genes revealed that 5-hydroxybenzimidazole, 5-methoxybenzimidazole, and 5-methoxy-6-methylbenzimidazole, all of which are lower ligands of cobamides produced by other organisms, are intermediates in the pathway. The bza gene content of several bacterial and archaeal genomes is consistent with experimentally determined structures of the benzimidazoles produced by these organisms, indicating that these genes can be used to predict cobamide structure. The identification of the bza genes thus represents the last remaining unknown component of the biosynthetic pathway for not only B12 itself, but also for three other cobamide lower ligands whose biosynthesis was previously unknown. Given the importance of cobamides in environmental, industrial, and human-associated microbial metabolism, the ability to predict cobamide structure may lead to an improved ability to understand and manipulate microbial metabolism.

  2. Glycan microarray analysis of Candida glabrata adhesin ligand specificity.

    Science.gov (United States)

    Zupancic, Margaret L; Frieman, Matthew; Smith, David; Alvarez, Richard A; Cummings, Richard D; Cormack, Brendan P

    2008-05-01

    The Candida glabrata genome encodes at least 23 members of the EPA (epithelial adhesin) family responsible for mediating adherence to host cells. To better understand the mechanism by which the Epa proteins contribute to pathogenesis, we have used glycan microarray analysis to characterize their carbohydrate-binding specificities. Using Saccharomyces cerevisiae strains surface-expressing the N-terminal ligand-binding domain of the Epa proteins, we found that the three Epa family members functionally identified as adhesins in Candida glabrata (Epa1, Epa6 and Epa7) bind to ligands containing a terminal galactose residue. However, the specificity of the three proteins for glycans within this class varies, with Epa6 having a broader specificity range than Epa1 or Epa7. This result is intriguing given the close homology between Epa6 and Epa7, which are 92% identical at the amino acid level. We have mapped a five-amino-acid region within the N-terminal ligand-binding domain that accounts for the difference in specificity of Epa6 and Epa7 and show that these residues contribute to adherence to both epithelial and endothelial cell lines in vitro.

  3. Structure and ligand recognition of class C GPCRs

    Institute of Scientific and Technical Information of China (English)

    Lei CHUN; Wen-hua ZHANG; Jian-feng LIU

    2012-01-01

    The G-protein-coupled receptors (GPCRs) are one of the largest super families of cell-surface receptors and play crucial roles in virtu-ally every organ system.One particular family of GPCRs,the class C GPCRs,is distinguished by a characteristically large extracellular domain and constitutive dimerization.The structure and activation mechanism of this family result in potentially unique ligand recognition sites,thereby offering a variety of possibilities by which receptor activity might be modulated using novel compounds.In the present article,we aim to provide an overview of the exact sites and structural features involved in ligand recognition of the class C GPCRs.Furthermore,we demonstrate the precise steps that occur during the receptor activation process,which underlie the possibilities by which receptor function may be altered by different approaches.Finally,we use four typical family members to illustrate orthosteric and allosteric sites with representative ligands and their corresponding therapeutic potential.

  4. Ligand-hole localization in oxides with unusual valence Fe.

    Science.gov (United States)

    Chen, Wei-Tin; Saito, Takashi; Hayashi, Naoaki; Takano, Mikio; Shimakawa, Yuichi

    2012-01-01

    Unusual high-valence states of iron are stabilized in a few oxides. A-site-ordered perovskite-structure oxides contain such iron cations and exhibit distinct electronic behaviors at low temperatures, e.g. charge disproportionation (4Fe⁴⁺ → 2Fe³⁺ + 2Fe⁵⁺) in CaCu₃Fe₄O₁₂ and intersite charge transfer (3Cu²⁺ + 4Fe³·⁷⁵⁺ → 3Cu³⁺ + 4Fe³⁺) in LaCu₃Fe₄O₁₂. Here we report the synthesis of solid solutions of CaCu₃Fe₄O₁₂ and LaCu₃Fe₄O₁₂ and explain how the instabilities of their unusual valence states of iron are relieved. Although these behaviors look completely different from each other in simple ionic models, they can both be explained by the localization of ligand holes, which are produced by the strong hybridization of iron d and oxygen p orbitals in oxides. The localization behavior in the charge disproportionation of CaCu₃Fe₄O₁₂ is regarded as charge ordering of the ligand holes, and that in the intersite charge transfer of LaCu₃Fe₄O₁₂ is regarded as a Mott transition of the ligand holes.

  5. Probing riboswitch-ligand interactions using thiamine pyrophosphate analogues.

    Science.gov (United States)

    Chen, Liuhong; Cressina, Elena; Dixon, Neil; Erixon, Karl; Agyei-Owusu, Kwasi; Micklefield, Jason; Smith, Alison G; Abell, Chris; Leeper, Finian J

    2012-08-14

    The Escherichia coli thiM riboswitch forms specific contacts with its natural ligand, thiamine pyrophosphate (TPP or thiamine diphosphate), allowing it to generate not only nanomolar binding affinity, but also a high degree of discrimination against similar small molecules. A range of synthetic TPP analogues have been used to probe each of the riboswitch-ligand interactions. The results show that the pyrimidine-sensing helix of thiM is exquisitely tuned to select for TPP by recognising the H-bonding donor and acceptors around its aminopyrimidine ring and also by forming π-stacking interactions that may be sensitive to the electronics of the ring. The central thiazolium ring of TPP appears to be more important for ligand recognition than previously thought. It may contribute to binding via long-range electrostatic interactions and/or by exerting an electron withdrawing effect on the pyrimidine ring, allowing its presence to be sensed indirectly and thereby allowing discrimination between thiamine (and its phosphate esters) and other aminopyrimidines found in vivo. The pyrophosphate moiety is essential for submicromolar binding affinity, but unexpectedly, it does not appear to be strictly necessary for modulation of gene expression.

  6. Ligand-Gated Ion Channels: Permeation and Activation1

    Science.gov (United States)

    Lynch, Joseph W.; Barry, Peter H.

    Ligand-gated ion channels (LGICs) are fast-responding channels in which the receptor, which binds the activating molecule (the ligand), and the ion channel are part of the same nanomolecular protein complex. This chapter will describe the properties and functions of the nicotinic acetylcholine LGIC superfamily, which play a critical role in the fast chemical transmission of electrical signals between nerve cells at synapses and between nerve and muscle cells at endplates. All the processing functions of the brain and the resulting behavioral output depend on chemical transmission across such neuronal interconnections. To describe the properties of the channels of this LGIC superfamily,we will mainly use two examples of this family of channels: the excitatory nicotinic acetylcholine receptor (nAChR) and the inhibitory glycine receptor (GlyR) channels. In the chemical transmission of electrical signals, the arrival of an electrical signal at the synaptic terminal of a nerve causes the release of a chemical signal—a neurotransmitter molecule (the ligand, also referred to as the agonist). The neurotransmitter rapidly diffuses across the very narrow 20-40 nm synaptic gap between the cells and binds to the LGIC receptors in the membrane of the target (postsynaptic) cell and generates a new electrical signal in that cell (e.g., Kandel et al., 2000). How this chemical signal is converted into an electrical one depends on the fundamental properties of LGICs and the ionic composition of the postsynaptic cell and its external solution.

  7. Using inositol as a biocompatible ligand for efficient transgene expression.

    Science.gov (United States)

    Zhang, Lei; Bellis, Susan L; Fan, Yiwen; Wu, Yunkun

    2015-01-01

    Transgene transfection techniques using cationic polymers such as polyethylenimines (PEIs) and PEI derivatives as gene vectors have shown efficacy, although they also have shortcomings. PEIs have decent DNA-binding capability and good cell internalization performance, but they cannot deliver gene payloads very efficiently to cell nuclei. In this study, three hyperbranched polyglycerol-polyethylenimine (PG6-PEI) polymers conjugated with myo-inositol (INO) molecules were developed. The three resulting PG6-PEI-INO polymers have an increased number of INO ligands per molecule. PG6-PEI-INO 1 had only 14 carboxymethyl INO (CMINO) units per molecule. PG6-PEI-INO 2 had approximately 130 CMINO units per molecule. PG6-PEI-INO 3 had as high as 415 CMINO units approximately. Mixing PG6-PEI-INO polymers with DNA produced compact nanocomposites. We then performed localization studies using fluorescent microscopy. As the number of conjugated inositol ligands increased in PG6-PEI-INO polymers, there was a corresponding increase in accumulation of the polymers within 293T cell nuclei. Transfection performed with spherical 293T cells yielded 82% of EGFP-positive cells when using PG6-PEI-INO 3 as the vehicle. Studies further revealed that extracellular adenosine triphosphate (eATP) can inhibit the transgene efficiency of PG6-PEI-INO polymers, as compared with PEI and PG6-PEI that were not conjugated with inositol. Our work unveiled the possibility of using inositol as an effective ligand for transgene expression.

  8. High affinity ligands for 'diazepam-insensitive' benzodiazepine receptors.

    Science.gov (United States)

    Wong, G; Skolnick, P

    1992-01-14

    Structurally diverse compounds have been shown to possess high affinities for benzodiazepine receptors in their 'diazepam-sensitive' (DS) conformations. In contrast, only the imidazobenzodiazepinone Ro 15-4513 has been shown to exhibit a high affinity for the 'diazepam-insensitive' (DI) conformation of benzodiazepine receptors. We examined a series of 1,4-diazepines containing one or more annelated ring systems for their affinities at DI and DS benzodiazepine receptors, several 1,4-diazepinone carboxylates including Ro 19-4603, Ro 16-6028 and Ro 15-3505 were found to possess high affinities (Ki approximately 2.6-20 nM) for DI. Nonetheless, among the ligands examined, Ro 15-4513 was the only substance with a DI/DS potency ratio approximately 1; other substances had ratios ranging from 13 to greater than 1000. Ligands with high to moderate affinities at DI were previously classified as partial agonists, antagonists, or partial inverse agonists at DS benzodiazepine receptors, but behaved as 'GABA neutral' (antagonist) substances at DI. The identification of several additional high affinity ligands at DI benzodiazepine receptors may be helpful in elucidating the pharmacological and physiological importance of these sites.

  9. Formyl peptide receptor chimeras define domains involved in ligand binding.

    Science.gov (United States)

    Perez, H D; Holmes, R; Vilander, L R; Adams, R R; Manzana, W; Jolley, D; Andrews, W H

    1993-02-05

    We have begun to study the structural requirements for the binding of formyl peptides to their specific receptors. As an initial approach, we constructed C5a-formyl peptide receptor chimeras. Unique (and identical) restriction sites were introduced within the transmembrane domains of these receptors that allowed for the exchange of specific areas. Four types of chimeric receptors were generated. 1) The C5a receptor was progressively substituted by the formyl peptide receptor. 2) The formyl peptide receptor was progressively substituted by the C5a receptor. 3) Specific domains of the C5a receptor were substituted by the corresponding domain of the formyl peptide receptor. 4) Specific domains of the formyl peptide receptor were replaced by the same corresponding domain of the C5a receptor. Wild type and chimeric receptors were transfected into COS 7 cells and their ability to bind formyl peptide determined, taking into account efficiency of transfection and expression of chimeric protein. Based on these results, a ligand binding model is presented in which the second, third, and fourth extracellular (and/or their transmembrane) domains together with the first transmembrane domain form a ligand binding pocket for formyl peptides. It is proposed that the amino-terminal domain plays a role by presumably providing a "lid" to the pocket. The carboxyl-terminal cytoplasmic tail appears to modulate ligand binding by regulating receptor affinity.

  10. Electrophilic Metal Alkyl Chemistry in New Ligand Environments

    Energy Technology Data Exchange (ETDEWEB)

    Jordan, Richard F. [University of Chicago

    2013-06-30

    The goals of this project were to design new electrophilic metal alkyl complexes and to exploit these systems in fundamental studies of olefin polymerization and other important and new catalytic reactions. A key target reaction is insertion copolymerization of olefins and polar CH2=CHX vinyl monomers such as vinyl halides and vinyl ethers. During the period covered by this report we (i) investigated the properties of ortho-alkoxy-arylphosphine ligands in Ni-based olefin polymerization catalysts, (ii) studied the synthesis of double-end-capped polyethylene using group 4 metal catalysts that contain tris-pyrazolylborate ligands, (iii) explored the ethylene insertion reactivity of group 4 metal tris-pyrazolyl-borate complexes, (iv) showed that (α-diimine)PdMe{sup +} species undergo multiple insertion of silyl vinyl ethers, (v) synthesized and explored the reactivity of base-free Ni benzyl complexes that contain ortho-phosphino-arene sulfonate ligands, (vi) established the mechanism of the reaction of vinyl chloride with (α-diimine)PdMe{sup +} catalysts, (vii) explored the role of cationic polymerization and insertion chemistry in the reactions of vinyl ethers with (α-diimine)PdMe{sup +} species, (viii) discovered a new class of self-assembled tetranuclear Pd catalysts that produce high molecular weight linear polyethylene and copolymerize ethylene and vinyl fluoride, and (ix) developed model systems that enabled investigation of cis-trans isomerization of {phosphine-sulfonate}Pd(II) complexes.

  11. 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.

  12. CREDO: a protein-ligand interaction database for drug discovery.

    Science.gov (United States)

    Schreyer, Adrian; Blundell, Tom

    2009-02-01

    Harnessing data from the growing number of protein-ligand complexes in the Protein Data Bank is an important task in drug discovery. In order to benefit from the abundance of three-dimensional structures, structural data must be integrated with sequence as well as chemical data and the protein-small molecule interactions characterized structurally at the inter-atomic level. In this study, we present CREDO, a new publicly available database of protein-ligand interactions, which represents contacts as structural interaction fingerprints, implements novel features and is completely scriptable through its application programming interface. Features of CREDO include implementation of molecular shape descriptors with ultrafast shape recognition, fragmentation of ligands in the Protein Data Bank, sequence-to-structure mapping and the identification of approved drugs. Selected analyses of these key features are presented to highlight a range of potential applications of CREDO. The CREDO dataset has been released into the public domain together with the application programming interface under a Creative Commons license at http://www-cryst.bioc.cam.ac.uk/credo. We believe that the free availability and numerous features of CREDO database will be useful not only for commercial but also for academia-driven drug discovery programmes.

  13. Coupling of Ligands to the Liposome Surface by Click Chemistry.

    Science.gov (United States)

    Spanedda, Maria Vittoria; De Giorgi, Marcella; Hassane, Fatouma Saïd; Schuber, Francis; Bourel-Bonnet, Line; Frisch, Benoît

    2017-01-01

    Click chemistry represents a new bioconjugation strategy that can be used to conveniently attach various ligands to the surface of preformed liposomes. This efficient and chemoselective reaction involves a Cu(I)-catalyzed azide-alkyne cycloaddition which can be performed under mild experimental conditions in aqueous media. Here we describe the application of a model click reaction to the conjugation, in a single step, of unprotected α-1-thiomannosyl ligands, functionalized with an azide group, to liposomes containing a terminal alkyne-functionalized lipid anchor. Excellent coupling yields have been obtained in the presence of bathophenanthroline disulfonate, a water soluble copper-ion chelator, acting as a catalyst. No vesicle leakage is triggered by this conjugation reaction and the coupled mannose ligands are exposed at the surface of the liposomes. The major limitation of Cu(I)-catalyzed click reactions is that this conjugation is restricted to liposomes made of saturated (phospho)lipids. To circumvent that constraint, an example of alternative copper-free azide-alkyne click reaction has been developed. Molecular tools and results are presented here.

  14. Synthesis, spectroscopic, thermogravimetric and antimicrobial studies of mixed ligands complexes

    Science.gov (United States)

    Mahmoud, Walaa H.; Mahmoud, Nessma F.; Mohamed, Gehad G.; El-Sonbati, Adel Z.; El-Bindary, Ashraf A.

    2015-09-01

    An interesting series of mixed ligand complexes have been synthesized by the reaction of metal chloride with guaifenesin (GFS) in the presence of 2-aminoacetic acid (HGly) (1:1:1 molar ratio). The elemental analysis, magnetic moments, molar conductance, spectral (UV-Vis, IR, 1H NMR and ESR) and thermal studies were used to characterize the isolated complexes. The molecular structure of GFS is optimized theoretically and the quantum chemical parameters are calculated. The IR showed that the ligand (GFS) acts as monobasic tridentate through the hydroxyl, phenoxy etheric and methoxy oxygen atoms and co-ligand (HGly) as monobasic bidentate through the deprotonated carboxylate oxygen atom and nitrogen atom of amino group. The molar conductivities showed that all the complexes are non-electrolytes except Cr(III) complex is electrolyte. Electronic and magnetic data proposed the octahedral structure for all complexes under investigation. ESR spectrum for Cu(II) revealed data which confirm the proposed structure. Antibacterial screening of the compounds were carried out in vitro on gram positive (Bacillus subtilis and Staphylococcus aureus), gram negative (Escherichia coli and Neisseria gonorrhoeae) bacteria and for in vitro antifungal activity against Candida albicans organism. However, some complexes showed more chemotherapeutic efficiency than the parent GFS drug. The complexes were also screened for their in vitro anticancer activity against the breast cell line (MFC7) and the results obtained showed that they exhibit a considerable anticancer activity.

  15. Ligand-protein docking using a quantum stochastic tunneling optimization method.

    Science.gov (United States)

    Mancera, Ricardo L; Källblad, Per; Todorov, Nikolay P

    2004-04-30

    A novel hybrid optimization method called quantum stochastic tunneling has been recently introduced. Here, we report its implementation within a new docking program called EasyDock and a validation with the CCDC/Astex data set of ligand-protein complexes using the PLP score to represent the ligand-protein potential energy surface and ScreenScore to score the ligand-protein binding energies. When taking the top energy-ranked ligand binding mode pose, we were able to predict the correct crystallographic ligand binding mode in up to 75% of the cases. By using this novel optimization method run times for typical docking simulations are significantly shortened.

  16. Detection of iron(III)-binding ligands originating from marine phytoplankton using cathodic stripping voltammetry.

    Science.gov (United States)

    Hasegawa, Hiroshi; Maki, Teruya; Asano, Kohnosuke; Ueda, Kentaro; Ueda, Kazumasa

    2004-01-01

    The sample preparation and analytical methodology are described for detecting biologically produced iron(III)-binding ligands in laboratory cultures of coastal marine phytoplankton. The iron(III)-binding ligands from the culture media were purified by passage through a column packing with a hydrophobic absorbent. The concentrations and stability constants of the ligands were determined by adsorptive cathodic stripping voltammetry with competitive ligand equilibration. The analytical results of the cultivated cultures suggest that eukaryotic phytoplankton would produce iron(III)-binding ligands in analogy with other microorganisms.

  17. High-affinity benzodiazepine receptor ligands among benzodiazepines and betacarbolines with different intrinsic activity

    Energy Technology Data Exchange (ETDEWEB)

    Yliniemelae, A.; Gynther, J. (Univ. of Kuopio (Finland)); Konschin, H.; Tylli, H. (Univ. of Helsinki (Finland)); Rouvinen, J. (Univ. of Joensuu (Finland))

    1989-01-01

    Structural and electrostatic features of diazepam, flumazenil, and methyl betacarboline-3-carboxylate (BCCM) have been investigated using the molecular superimposition method. These high-affinity benzodiazepine (BZ) receptor ligands are structurally unrelated and they have different intrinsic activity. These ligands are superimposed in such a way that common structural and electrostatic features essential for the high receptor binding affinity overlap. In addition to this binding pharmacophore, there are roughly three separate binding zones in the BZ receptor, one for each class of ligands. The intrinsic activity of BZ receptor ligands depends on the molecular structures and the way the ligand approaches the receptor.

  18. Mixed-ligand complexes of ruthenium(II) incorporating a diazo ligand: Synthesis, characterization and DNA binding

    Indian Academy of Sciences (India)

    Megha S Deshpande; Avinash S Kumbhar

    2005-03-01

    Mixed-ligand complexes of the type [Ru(N-N)2(dzdf)]Cl2, where N-N is 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen) and 9-diazo-4,5-diazafluorene (dzdf), have been synthesized and characterized by elemental analysis, UV-Vis, IR and NMR spectroscopy. Binding of these complexes with calf thymus DNA (CT-DNA) has been investigated by absorption spectroscopy, steady-state emission spectroscopy and viscosity measurements. The experimental results indicate that the size and shape of the intercalating ligands have marked effect on the binding affinity of the complexes to CT-DNA. The complex [Ru(phen)2(dzdf)]Cl2 binds with CT-DNA through an intercalative binding mode, while the complex [Ru(bpy)2(dzdf)]Cl2 binds electrostatically.

  19. Synthesis of nanoparticle/ligand composite thin films by sequential ligand self assembly and surface complex reduction.

    Science.gov (United States)

    Muench, Falk; Fuchs, Anne; Mankel, Eric; Rauber, Markus; Lauterbach, Stefan; Kleebe, Hans-Joachim; Ensinger, Wolfgang

    2013-01-01

    Nanocomposite thin films consisting of ligand-connected metal nanoparticles were deposited by iteration of ligand assembly, surface complex formation and reduction. This novel and convenient approach combines characteristics of the layer-by-layer (LbL) and the successive ion layer adsorption and reaction (SILAR) techniques. In contrast to classical LbL assembly, the nanoparticle formation is performed in situ, avoiding separate reduction, protection and attachment steps. To demonstrate the versatility of the approach, different metal precursors (Pd, Ag and Au salts) and linkers (1,2-ethanedithiol, 1,4-benzenedithiol and polythiol) were applied. The formation of dithiol-linked nanoparticle films was confirmed by TEM and XPS. By combining the deposition protocol with ion track etched polycarbonate templates, nanotubes and nanowires with high aspect ratios of up to 300 could be fabricated.

  20. Micellar-enhanced ultrafiltration process (MEUF) for removing copper from synthetic wastewater containing ligands.

    Science.gov (United States)

    Liu, Chuan-Kun; Li, Chi-Wang; Lin, Ching-Yu

    2004-11-01

    The effects of the type and concentration of ligands on the removal of Cu by micellar-enhanced ultrafiltration (MEUF) with the help of either anionic or cationic surfactants were investigated. The removal efficiency of copper by anionic surfactant-(SDS-) MEUF depends on the ligand-to-Cu ratio and the ligand-to-Cu complexation constant. At fixed ligand-to-Cu ratio, the Cu removal efficiency decreases in the order of citric acid>NTA>EDTA, which is the reverse order of Cu-ligand complexation constants for these ligands. Increasing SDS-ligand ratios from 12 to 60 at fixed ligand concentration did not improve copper removal efficiency. The cationic surfactant, CPC, enhances Cu removal efficiency in systems with condition of ligand-copper ratios higher than 1.0, where Cu removal is not very efficient using SDS-MEUF process. The Cu removal efficiency with CPC-MEUF depends on both the ligand-to-Cu ratio and the type of ligands.