Improving the stability of coal slurries: Quarterly progress report for the period September 15, 1987-December 15, 1987

Energy Technology Data Exchange (ETDEWEB)

Fogler, H.S.

1987-01-01

Gum tragacanth, GT changes the conformation on the negative surface of sulfate polystyrene latex particles as the amount of charge in GT alters with pH. Also, it had been indicated that the polygalacturonic acid, PGUA which constitutes the core of GT molecules is responsible for the conformational change. In order to find how this conformational change is related to the adsorption affinity between the surface and the polyelectrolyte, the positively charged amidine polystyrene latex particles were employed. The stability study showed that the PGUA can also stabilize the positively charged particles and that the stability of the amidine latex is virtually independent of pH whereas the stability of the sulfate latex is dependent on pH. The adsorption study indicated that this independence of stability on pH for the amidine latex is due to the fact that the strong adsorption affinity between the positive surface and the negative polyelectrolyte gives the similar conformation regardless of pH. 6 refs., 8 figs., 2 tabs.

Solvent/oxidant-switchable synthesis of multisubstituted quinazolines and benzimidazoles via metal-free selective oxidative annulation of arylamidines.

Science.gov (United States)

Lin, Jian-Ping; Zhang, Feng-Hua; Long, Ya-Qiu

2014-06-06

A fast and simple divergent synthesis of multisubstituted quinazolines and benzimidazoles was developed from readily available amidines, via iodine(III)-promoted oxidative C(sp(3))-C(sp(2)) and C(sp(2))-N bond formation in nonpolar and polar solvents, respectively. Further selective synthesis of quinazolines in polar solvent was realized by TEMPO-catalyzed sp(3)C-H/sp(2)C-H direct coupling of the amidine with K2S2O8 as the oxidant. No metal, base, or other additives were needed.

Simple and Efficient Procedure for Synthesis of N'-Arylamidines Using Trimethylaluminum

International Nuclear Information System (INIS)

Korbad, Balaji L.; Lee, Sanghyeup

2013-01-01

In conclusion, we have developed simple and efficient procedure for the synthesis of N'-arylamidines using tri-methylaluminum, nitriles and aryl amines under mild condition. Aliphatic, aromatic nitriles were reacted well with a variety of aromatic amine to afford corresponding amidines in good to high yields. Amidines are an important class of compounds that have wide range of application in the fields of catalyst design, material science, medicinal chemistry and also shown the promising anti-inflammatory and analgesic activity. They are valuable synthons for synthesis of various heterocyclic compounds. In addition, recent studies have demonstrated their capacity to fix carbon dioxide

B-H Bond Activation by an Amidinate-Stabilized Amidosilylene: Non-Innocent Amidinate Ligand.

Science.gov (United States)

Khoo, Sabrina; Shan, Yu-Liang; Yang, Ming-Chung; Li, Yongxin; Su, Ming-Der; So, Cheuk-Wai

2018-05-21

The activation of B-H and B-Cl bonds in boranes by base-stabilized low-valent silicon compounds is described. The reaction of the amidinato amidosilylene-borane adduct [L{Ar(Me 3 Si)N}SiBH 3 ] [1; L = PhC(N tBu) 2 , and Ar = 2,6- iPr 2 C 6 H 3 ] with MeOTf in toluene at room temperature formed [L{Ar(Me 3 Si)N}SiBH 2 OTf] (2). [LSiN(SiMe 3 )Ar] in compound 2 then underwent a B-H bond activation with BH 2 OTf in refluxing toluene to afford the B-H bond activation product [LB(H)Si(H)(OTf){N(SiMe 3 )Ar}] (3). On the other hand, when compound 2 was reacted with 4-dimethylaminopyridine in refluxing toluene, another B-H bond activation product [(μ-κ1:κ1-L)B(H)(DMAP)Si(H){N(Ar)SiMe 3 }]OTf (4) was afforded. Mechanistic studies show that "(μ-κ1:κ1-L)B(H)(OTf)Si(H){N(Ar)SiMe 3 }" (2A) is the key intermediate in the reactions mentioned above. The formation of 2A is further evidenced by the activation of the B-Cl bond in PhBCl 2 by the amidinato silicon(I) dimer [LSi:] 2 to form the B-Cl bond activation product [(μ-κ1:κ1-L)B(Cl)(Ph)Si(Cl)] 2 (6). Compounds 2-4 and 6 were characterized by nuclear magnetic resonance spectroscopy and X-ray crystallography.

Fabrication of CO2 Facilitated Transport Channels in Block Copolymer through Supramolecular Assembly

Directory of Open Access Journals (Sweden)

Yao Wang

2014-05-01

Full Text Available In this paper, the molecule 12-amidine dodecanoic acid (M with ending groups of carboxyl and amidine groups respectively was designed and synthesized as CO2-responsive guest molecules. The block copolymer polystyrene-b-polyethylene oxide (PS-b-PEO was chosen as the host polymer to fabricate a composite membrane through H-bonding assembly with guest molecule M. We attempted to tune the phase separation structure of the annealed film by varying the amount of M added, and investigated the nanostructures via transmission electron microscope (TEM, fourier transform infrared (FT-IR etc. As a result, a reverse worm-like morphology in TEM image of bright PS phase in dark PEO/M matrix was observed for PS-b-PEO/M1 membrane in which the molar ratio of EO unit to M was 1:1. The following gas permeation measurement indicated that the gas flux of the annealed membranes dramatically increased due to the forming of ordered phase separation structure. As we expected, the obtained composite membrane PS-b-PEO/M1 with EO:M mole ratio of 1:1 presented an evident selectivity for moist CO2 permeance, which is identical with our initial proposal that the guest molecule M in the membranes will play the key role for CO2 facilitated transportation since the amidine groups of M could react reversibly with CO2 molecules in membranes. This work provides a supramolecular approach to fabricating CO2 facilitated transport membranes.

Facile nanofibrillation of chitin derivatives by gas bubbling and ultrasonic treatments in water.

Science.gov (United States)

Tanaka, Kohei; Yamamoto, Kazuya; Kadokawa, Jun-ichi

2014-10-29

In this paper, we report that nanofiber network structures were constructed from chitin derivatives by gas bubbling and ultrasonic treatments in water. When chitin was first subjected to N2 gas bubbling with ultrasonication in water, the SEM images of the product showed nanofiber network morphology. However, nanofiber network was not re-constructed by the same N2 gas bubbling and ultrasonic treatments after agglomeration. We then have paid attention to an amidine group to provide the agglomeration-nanofibrillation behavior of chitin derivatives. An amidinated chitin was synthesized by the reaction of the amino groups in a partially deacetylated chitin with N,N-dimethylacetamide dimethyl acetal, which was subjected to CO2 gas bubbling and ultrasonic treatments in water to convert into an amidinium chitin by protonation. The SEM images of the product clearly showed nanofiber network morphology. We further examined re-nanofibrillation of the agglomerated material, which was obtained by mixing the nanofibrillated amidinium chitin with water, followed by drying under reduced pressure. Consequently, the material was re-nanofibrillated by N2 gas bubbling with ultrasonication in water owing to electrostatic repulsion between the amidinium groups. Furthermore, deprotonation of the amidinium chitin and re-protonation of the resulting amidinated chitin were conducted by alkaline treatment and CO2 gas bubbling-ultrasonic treatments, respectively. The material showed the agglomeration-nanofibrillation behavior during the processes. Copyright © 2014 Elsevier Ltd. All rights reserved.

pyridines and imidazo[1,2-b]pyridazines

Indian Academy of Sciences (India)

Hongli Fan

2018-05-07

May 7, 2018 ... School of Chemistry and Chemical Engineering, Heze University, 2269 Daxue ... approach to the synthesis of 3-substituted imidazo[1,2- ...... and Sharratt A P 1991 Chemistry of amidines. Part. 1. Determination of the site of ...

Synthesis and properties of the para-trimethylammonium analogues of green fluorescence protein (GFP) chromophore: The mimic of protonated GFP chromophore.

Science.gov (United States)

Fanjiang, Ming-Wei; Li, Ming-Ju; Sung, Robert; Sung, Kuangsen

2018-04-01

At low pH, protons from the external, bulk solution can protonate the phenoxide group of the p-HBDI chromophore in wild-type green fluorescent protein (wtGFP) and its mutants, and likely continue to tentatively protonate the phenol hydroxyl group of the same chromophores. Because the protonated GFP chromophore is a transient, we prepare the stable p-trimethylammonium analogues (2a and 2b) of the GFP chromophore to mimic it and explore their properties. What we found is that the p-trimethylammonium analogues of the GFP chromophore have the highly electrophilic amidine carbon, blue-shifted electronic absorption, smaller molar absorptivity, smaller fluorescent quantum yield, and faster E-Z thermoisomerization rate. The amidine carbon of the p-trimethylammonium analogue (2b) of the GFP chromophore is the only site that is attacked by very weak nucleophile of water, resulting in ring-opening of the imidazolinone moiety. The half-life of its decay rate in D 2 O is around 33 days. Actually, acid-catalyzed hydrolysis of p-HBDI also results in ring-opening of the imidazolinone moiety. The ratio of the acid-catalyzed hydrolysis rate constants [k obs (p-HBDI)/k obs (1b)] between p-HBDI and 1b (p-dimethylammonium analogue of the GFP chromophore) is dramatically increased from 0.30 at pH = 2 to 0.63 at pH = 0. This is the evidence that more and more phenol hydroxyl groups of p-HBDI are tentatively protonated in a low-pH aqueous solution and that accelerates hydrolysis of p-HBDI in the way similar to the quaternary ammonium derivatives 2a and 2b in water. With this view point, 2a and 2b still can partially mimic the cationic p-HBDI with the protonated phenol hydroxyl group. Implication of the experiment is that the amidine carbon of the chromophore in wtGFP and its mutants at very low pH should be highly electrophilic. Whether ring-opening of the imidazolinone moiety of the GFP chromophore would occur or not depends on if water molecules can reach the amidine carbon of

Carbon-14 labelled nitrogen heterocycles; the syntheses of three phosphodiesterase inhibitors

International Nuclear Information System (INIS)

Lawrie, K.W.M.; Novelli, C.E.A.; Saunders, David

1995-01-01

The syntheses of three heterocyclic phosphodiesterase inhibitors are described from a common radiolabelled precursor, namely 2-propoxybenzo[cyano- 14 C] nitrile. Conversion of the nitrile to the corresponding methyl ketone or amidine allows elaboration of the heterocycles radiolabelled within the ring systems. (Author)

Journal of Chemical Sciences | Indian Academy of Sciences

Indian Academy of Sciences (India)

Synthesis of 2-(oxadiazolo, pyrimido, imidazolo, and benzimidazolo) substituted analogues of 1,4-benzodiazepin-5-carboxamides linked through a phenoxyl bridge ... Exceedingly facile single-step expedient protocols based on the versatility and reactivity of corresponding intermediates amidine and imidate (8 and 9), ...

In situ alcoholysis of triacylglycerols by application of switchable-polarity solvents. A new derivatization procedure for the gas-chromatographic analysis of vegetable oils.

Science.gov (United States)

Saliu, Francesco; Orlandi, Marco

2013-10-01

We describe a new use of switchable-polarity solvents for the simultaneous derivatization and extraction of triacylglycerols from vegetable oils before gas-chromatographic analysis. Different equimolecular mixtures of the commercially available amidine 1,8-diazabicyclo[5.4.0]undec-7-ene and n-alkyl alcohols were tested. Triolein was used as a model compound. Very good results were achieved by using butanol (recovery of butyl oleate was 89 ± 4%). The procedure was applied for the characterization of the fatty acid profile of different vegetable oils. No statistically significant differences from the results obtained with the application of two traditional methods were evidenced. Moreover, the use of switchable-polarity solvents showed many advantages: owing to the basicity of the amidines, no catalyst was required; the transterification reaction was conducted under mild conditions, one step and in situ; no particular matrix interferences were evidenced; the solvent was recovered.

Carbon-14 labelled nitrogen heterocycles; the syntheses of three phosphodiesterase inhibitors

Energy Technology Data Exchange (ETDEWEB)

Lawrie, K.W.M.; Novelli, C.E.A.; Saunders, David [SmithKline Beecham Pharmaceuticals Research and Development, Harlow (United Kingdom). Synthetic Isotope Chemistry Dept.; Coates, W.J. [SmithKline Beecham Pharmaceuticals Research and Development, Welwyn (United Kingdom)

1995-09-01

The syntheses of three heterocyclic phosphodiesterase inhibitors are described from a common radiolabelled precursor, namely 2-propoxybenzo[cyano-{sup 14}C] nitrile. Conversion of the nitrile to the corresponding methyl ketone or amidine allows elaboration of the heterocycles radiolabelled within the ring systems. (Author).

Journal of Chemical Sciences | Indian Academy of Sciences

Indian Academy of Sciences (India)

... Refresher Courses · Symposia · Live Streaming. Home; Journals; Journal of Chemical Sciences; Volume 128; Issue 6. Amidinate Ligands in Zinc coordination sphere: Synthesis and structural diversity. SRINIVAS ANGA INDRANI BANERJEE TARUN K PANDA. Regular Article Volume 128 Issue 6 June 2016 pp 867-873 ...

Reaction of Tosylmethyl Isocyanide with N-Heteroaryl Formamidines: an Alternative Approach to the Synthesis of N-Heteroaryl Tosylimidazoles

Energy Technology Data Exchange (ETDEWEB)

Gomezgarcia, Omar; Salgadozamora, Hector; Reyesarellano, Aliciam; Camposaldrete, Elena; Peraltacruz, Javier [Departamento Quimica Organica, Colonia (Mexico)

2013-09-15

In conclusion, an alternative procedure was developed under mild conditions for the synthesis of 2-(4-tosylimidazo-1-yl)pyridines and pyrimidines by the reaction of TosMIC with the corresponding heteroaryl N,N'-dimethyl form-amidines. This approach does not involve a nucleophilic displacement of a leaving group and constitutes a further application of amidines, in which TosMIC acts as both a nucleophile and an electrophile on the heteroaryl formamidine. This process offers advantages over previously reported procedures. Tosyl methyl isocyanide (TosMIC), a multipurpose commercially available 3-unit synthon introduced by Van Leusen, reacts with a variety of groups to give heterocycles. It is important to emphasize that treatment of TosMIC with various functional groups leads to the formation of the imidazole nucleus, such as is the case with imines, imidoyl chlorides, isothiocyanates, nitrile and ethoxy methylene amino. However, only the latter group yields N-heterocycle imidazoles.

Chirality- and sequence-selective successive self-sorting via specific homo- and complementary-duplex formations

Science.gov (United States)

Makiguchi, Wataru; Tanabe, Junki; Yamada, Hidekazu; Iida, Hiroki; Taura, Daisuke; Ousaka, Naoki; Yashima, Eiji

2015-01-01

Self-recognition and self-discrimination within complex mixtures are of fundamental importance in biological systems, which entirely rely on the preprogrammed monomer sequences and homochirality of biological macromolecules. Here we report artificial chirality- and sequence-selective successive self-sorting of chiral dimeric strands bearing carboxylic acid or amidine groups joined by chiral amide linkers with different sequences through homo- and complementary-duplex formations. A mixture of carboxylic acid dimers linked by racemic-1,2-cyclohexane bis-amides with different amide sequences (NHCO or CONH) self-associate to form homoduplexes in a completely sequence-selective way, the structures of which are different from each other depending on the linker amide sequences. The further addition of an enantiopure amide-linked amidine dimer to a mixture of the racemic carboxylic acid dimers resulted in the formation of a single optically pure complementary duplex with a 100% diastereoselectivity and complete sequence specificity stabilized by the amidinium–carboxylate salt bridges, leading to the perfect chirality- and sequence-selective duplex formation. PMID:26051291

Structural analysis of d(GCAATTGC)2 and its complex with berenil by nuclear magnetic resonance spectroscopy

International Nuclear Information System (INIS)

Yoshida, Mitsuru; Banville, D.L.; Shafer, R.H.

1990-01-01

The structures of d(GCAATTGC) 2 and its complex with berenil in solution were analyzed by two-dimensional 1 H NMR spectroscopy. Intra- and internucleotide nuclear Overhauser effect (NOE) connectivities demonstrate that the octanucleotide duplex is primarily in the B conformation. Binding with berenil stabilizes the duplex with respect to thermal denaturation by about 10 degree C, based on the appearance of the imino proton signals. The berenil-d(GCAATTGC) 2 system is in fast exchange on the NMR time scale. The two-dimensional NMR data reveal that berenil binds in the minor groove of d(GCAATTGC) 2 . The aromatic drug protons are placed within 5 angstrom of the H2 proton of both adenines, the H1', H5', and H5 double-prime of both thymidines, and the H4', H5', and H5 double-prime of the internal guanosine. The amidine protons on berenil are also close to the H2 proton of both adenines. The duplex retains an overall B conformation in the complex with berenil. At 18 degree C, NOE contacts at longer mixing times indicate the presence of end-to-end association both in the duplex alone and also in its complex with berenil. These intermolecular contacts either vanished or diminished substantially at 45 degree C. Two molecular models are proposed for the berenil-(GCAATTGC) 2 complex; one has hydrogen bonds between the berenil amidine protons and the carbonyl oxygen, O2, of the external thymines, and the other has hydrogen bonds between the drug amidine protons and the purine nitrogen, N3, of the internal adenines. Quantitative analysis of the NOE data favors the second model

Direct electrochemical imidation of aliphatic amines via anodic oxidation.

Science.gov (United States)

Zhang, Li; Su, Ji-Hu; Wang, Sujing; Wan, Changfeng; Zha, Zhenggen; Du, Jiangfeng; Wang, Zhiyong

2011-05-21

Direct electrochemical synthesis of sulfonyl amidines from aliphatic amines and sulfonyl azides was realized with good to excellent yields. Traditional tertiary amine substrates were broadened to secondary and primary amines. The reaction intermediates were observed and a reaction mechanism was proposed and discussed. © The Royal Society of Chemistry 2011

Reactivity of nitriles

International Nuclear Information System (INIS)

Kukushkin, Yu.N.

1987-01-01

Reactivity of coordination nitriles in transition metal (Ru, Mo, W, Zr, Hf) complexes, namely: transformation of nitriles of the first coordination sphere into N-acyl-substituted amides, amidines, nitrile interaction; with water, alkalines, alcoholes, hydrogen, azide and cyanide ions is considered. Introduction of acetonitrile molecule to uranium (4)-carbon double bond is discussed

Fabrication of a Cu/Ni stack in supercritical carbon dioxide at low-temperature

Energy Technology Data Exchange (ETDEWEB)

Rasadujjaman, Md, E-mail: rasadphy@duet.ac.bd [Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 4-3-11 Takeda, Kofu, Yamanashi 400-8511 (Japan); Department of Physics, Dhaka University of Engineering & Technology, Gazipur 1700 (Bangladesh); Watanabe, Mitsuhiro [Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 4-3-11 Takeda, Kofu, Yamanashi 400-8511 (Japan); Sudoh, Hiroshi; Machida, Hideaki [Gas-Phase Growth Ltd., 2-24-16 Naka, Koganei, Tokyo 184-0012 (Japan); Kondoh, Eiichi [Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 4-3-11 Takeda, Kofu, Yamanashi 400-8511 (Japan)

2015-09-30

We report the low-temperature deposition of Cu on a Ni-lined substrate in supercritical carbon dioxide. A novel Cu(I) amidinate precursor was used to reduce the deposition temperature. From the temperature dependence of the growth rate, the activation energy for Cu growth on the Ni film was determined to be 0.19 eV. The films and interfaces were characterized by Auger electron spectroscopy. At low temperature (140 °C), we successfully deposited a Cu/Ni stack with a sharp Cu/Ni interface. The stack had a high adhesion strength (> 1000 mN) according to microscratch testing. The high adhesion strength originated from strong interfacial bonding between the Cu and the Ni. However, at a higher temperature (240 °C), significant interdiffusion was observed and the adhesion became weak. - Highlights: • Cu/Ni stack fabricated in supercritical CO{sub 2} at low temperature. • A novel Cu(I) amidinate precursor was used to reduce the deposition temperature. • Adhesion strength of Cu/Ni stack improved dramatically. • Fabricated Cu/Ni stack is suitable for Cu interconnections in microelectronics.

Chemist makes enhanced oil, oilsands extraction, greener using waste CO2

International Nuclear Information System (INIS)

Harrison, L.

2009-01-01

The Canada Research Chair of green Chemistry at Queen's University and his team of researchers has developed a reversible method of tying together and then separating oil and water using carbon dioxide (CO 2 ). This development has led to the ability to switch back and forth between surfactant and demulsifier. The surfactant used in the studies was a long-chain amidine made of a CO 2 -activated, air-deactivated soap-like compound. CO 2 was bubbled through the amidine to make it act like a surfactant. It was deactivated when CO 2 was removed by applying air. The technology for the switchable surfactant has potential as an inexpensive, environmentally sound alternative to existing oil recovery methods that use large quantities of toxic byproducts. It also enables more water recycling. Other applications include cleaning up oil spills and degreasing metal equipment or surfaces. The idea came to the researcher when working in Japan with a Nobel Prize winning chemist who studied the use of supercritical CO 2 as a solvent for chemical reactions. 1 ref., 1 fig

Zirconium bisamidinate complexes with sterically demanding ligands : structure, solution dynamics, and reactivity

NARCIS (Netherlands)

Otten, Edwin; Dijkstra, Peter; Visser, Cindy; Meetsma, Auke; Hessen, Bart

2005-01-01

Bisamidinate zirconium dichloride and dimethyl complexes with the sterically demanding amidinate ligands [PhC(NAr)(2))](-) (A) and [PhC(NAr)(NAr')](-) (B) (Ar = 2,6-(Pr2C6H3)-Pr-i; Ar' = 2,6-Me2C6H3) were prepared. The steric demand of ligand A induces the unusual trans geometry in

Synthesis and characterization of chiral thorium(IV) and uranium(IV) benzamidinate complexes

Energy Technology Data Exchange (ETDEWEB)

Schoene, Sebastian; Maerz, Juliane; Kaden, Peter; Patzschke, Michael; Ikeda-Ohno, Atsushi [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Chemistry of the F-Elements

2017-06-01

Two chiral benzamidinate complexes of tetravalent actinides (Th(IV) and U(IV)) were synthesized using a salt metathesis reaction of the corresponding actinide(IV) tetrachlorides and the potassium salt of the chiral benzamidine (S,S)-N,N-Bis-(1-phenylethyl)-benzamidine ((S)-HPEBA). The structure of the complexes was determined with single crystal X-ray diffraction. These are the first examples of chiral amidinate complexes of actinides.

Synthesis of Novel Aliphatic N-sulfonylamidino Thymine Derivatives by Cu(I)-catalyzed Three-component Coupling Reaction

OpenAIRE

Krstulović, Luka; Ismaili, Hamit; Višnjevac, Aleksandar; Glavaš-Obrovac, Ljubica; Žinić, Biserka

2012-01-01

A series of new aliphatic N-sulfonylamidino thymine derivatives containing nucleobase, N-sulfonyl and amidine pharmacophores in the structure were synthesized by Cu(I)-catalyzed threecomponent coupling of 1-propargyl thymine, benzenesulfonyl azides and amines or ammonium salts. Preliminary in vitro antitumor screening (human cervix adenocarcinoma -HeLa and leukemia cells - Jurkat) revealed promising activities of N,N-diethyl- (2) and N-4-cyanobenzyl- (6) derivatives of 4-acetamido...

Surprisingly Different Reaction Behavior of Alkali and Alkaline Earth Metal Bis(trimethylsilyl)amides toward Bulky N-(2-Pyridylethyl)-N'-(2,6-diisopropylphenyl)pivalamidine.

Science.gov (United States)

Kalden, Diana; Oberheide, Ansgar; Loh, Claas; Görls, Helmar; Krieck, Sven; Westerhausen, Matthias

2016-07-25

N-(2,6-Diisopropylphenyl)-N'-(2-pyridylethyl)pivalamidine (Dipp-N=C(tBu)-N(H)-C2 H4 -Py) (1), reacts with metalation reagents of lithium, magnesium, calcium, and strontium to give the corresponding pivalamidinates [(tmeda)Li{Dipp-N=C(tBu)-N-C2 H4 -Py}] (6), [Mg{Dipp-N=C(tBu)-N-C2 H4 -Py}2 ] (3), and heteroleptic [{(Me3 Si)2 N}Ae{Dipp-N=C(tBu)-N-C2 H4 -Py}], with Ae being Ca (2 a) and Sr (2 b). In contrast to this straightforward deprotonation of the amidine units, the reaction of 1 with the bis(trimethylsilyl)amides of sodium or potassium unexpectedly leads to a β-metalation and an immediate deamidation reaction yielding [(thf)2 Na{Dipp-N=C(tBu)-N(H)}] (4 a) or [(thf)2 K{Dipp-N=C(tBu)-N(H)}] (4 b), respectively, as well as 2-vinylpyridine in both cases. The lithium derivative shows a similar reaction behavior to the alkaline earth metal congeners, underlining the diagonal relationship in the periodic table. Protonation of 4 a or the metathesis reaction of 4 b with CaI2 in tetrahydrofuran yields N-(2,6-diisopropylphenyl)pivalamidine (Dipp-N=C(tBu)-NH2 ) (5), or [(thf)4 Ca{Dipp-N=C(tBu)-N(H)}2 ] (7), respectively. The reaction of AN(SiMe3 )2 (A=Na, K) with less bulky formamidine Dipp-N=C(H)-N(H)-C2 H4 -Py (8) leads to deprotonation of the amidine functionality, and [(thf)Na{Dipp-N=C(H)-N-C2 H4 -Py}]2 (9 a) or [(thf)K{Dipp-N=C(H)-N-C2 H4 -Py}]2 (9 b), respectively, are isolated as dinuclear complexes. From these experiments it is obvious, that β-metalation/deamidation of N-(2-pyridylethyl)amidines requires bases with soft metal ions and also steric pressure. The isomeric forms of all compounds are verified by single-crystal X-ray structure analysis and are maintained in solution. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

(E-N-[Cyclopentyl(morpholin-4-ylmethylidene]-4-fluorobenzenesulfonamide

Directory of Open Access Journals (Sweden)

Ilya Efimov

2016-01-01

Full Text Available The title compound, C16H21FN2O3S, was obtained from the reaction between sulfonyl azide, cyclohexanone and morpholine. The bond lengths at the amidine N—C—N grouping are similar [1.326 (3 and 1.338 (3 Å], indicating significant conjugation. The cyclopentyl moiety displays disorder of one of the methylene groups into two orientations with occupancy coefficients 0.75/0.25. No shortened intermolecular contacts in the crystal are observed.

Amphoteric Borylketenimines: Versatile Intermediates in the Synthesis of Borylated Heterocycles.

Science.gov (United States)

Kaldas, Sherif J; O'Keefe, Kowan T V; Mendoza-Sanchez, Rodrigo; Yudin, Andrei K

2017-07-21

We report the first synthesis of amphoteric borylketenimines from ethynyl N-methyliminodiacetic acid (MIDA) boronate and sulfonyl azides via copper catalysis. In situ trapping of these intermediates with various nucleophiles provided access to novel borylated azetidimines, iminocoumarins, amides, iminooxetanes, and amidines. The described strategy based on borylketenimines offers high levels of chemo- and regioselectivity, enabling the synthesis of unprecedented borylated molecules. This work highlights the unexplored utility of borylketenimines in the synthesis of potentially bioactive molecules. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A straightforward and efficient synthesis of 3-(pyrimidinyl)propanoates from levulinic acid

OpenAIRE

Flores,Alex F. C.; Malavolta,Juliana L.; Souto,Alynne A.; Goularte,Rayane B.; Flores,Darlene C.; Piovesan,Luciana A.

2013-01-01

The cyclocondensation of methyl 7,7,7-trifluoro-4-methoxy-6-oxo-4-heptenoate and methyl 7,7,7-trichloro-4-methoxy-6-oxo-4-heptenoate, derived from levulinic acid with amidines [NH2CONH2, NH2CR(NH) (R = H, Me, Ph, NH2, SMe and 1H-pyrazol-1-yl), 5-amino-3-methyl1H-pyrazol and 2-aminothiazole] into pyrimidine and pyrimidine-like derivatives as a new type of glutamate-like 3-(trihalomethylatedpyrimidinyl)propanoate is reported. Preparation of 3-(trihalomethylatedpyrimidinyl) propanohydrazides is ...

Chemistry of polyhalogenated nitrobutadienes, 10: Synthesis of highly functionalized heterocycles with a rigid 6-amino-3-azabicyclo[3.1.0]hexane moiety

Directory of Open Access Journals (Sweden)

Viktor A. Zapol’skii

2012-04-01

Full Text Available The nitropolychlorobutadienes 3, 4 are valuable building blocks for various amination and successive heterocyclization products. Nucleophilic substitution reactions of the partially protected, bioactive amines 1, 2 with either vinyl, imidoyl or carbonyl chlorides result in the formation of the enamines 11, 12, 13, 16, 25, the amidine 6, and the amides 20, 21, respectively. In the following, cyclization to the highly functionalized pyrazoles 27, 28, pyrimidine 26 and pyridopyrimidine 24 succeeded. Deprotection of 21, 12 and 28 proved to be only partially feasible.

Modification of dispersibility of nanodiamond by grafting of polyoxyethylene and by the introduction of ionic groups onto the surface via radical trapping

International Nuclear Information System (INIS)

Cha, I.; Hashimoto, K.; Fujiki, K.; Yamauchi, T.; Tsubokawa, N.

2014-01-01

To improve the dispersibility of polycrystalline nanodiamond (ND) in solvents, the grafting of polymers and introduction of ionic groups onto ND surface via radical trapping by ND surface were investigated. The grafting of polyoxyethylene (POE) onto ND surface by trapping of POE radicals formed by the thermal decomposition of POE macro azo-initiator (Azo-POE) was examined. The polymer radicals formed by the thermal decomposition of Azo-POE were successfully trapped by ND surface to give POE-grafted ND. The effect of temperature on the grafting of POE onto ND was discussed. In addition, the introduction of cationic protonated amidine groups onto ND was achieved by the trapping of radicals bearing protonated amidine groups formed by thermal decomposition of 2,2′-azobis(2-methylpropionamidine)dihydrochloride (AMPA). The anionic carboxylate groups was introduced onto ND surface by the trapping of the radicals bearing carboxyl groups formed by thermal decomposition of 4,4′-azobis(4-cyonovaleric acid) (ACVA) followed by the treatment with NaOH aqueous solution. The dispersibility of ND in water was remarkably improved by the grafting of POE, based on the steric hindrance of polymer chains and by the introduction of ionic groups, based on the ionic repulsion, onto ND surface. - Highlights: • Grafting of PEG onto nanodiamond was achieved by radical trapping. • Introduction of ionic groups onto nanodiamond was achieved by radical trapping. • Nanodiamond was dispersed by PEG grafting based on steric hindrance of PEG chains. • Nanodiamond was dispersed by introduction of ionic groups based on ionic repulsion

Modification of dispersibility of nanodiamond by grafting of polyoxyethylene and by the introduction of ionic groups onto the surface via radical trapping

Energy Technology Data Exchange (ETDEWEB)

Cha, I. [Graduate School of Science and Technology, Niigata University, 8050, Ikarashi, 2-no-cho, Nishi-ku, Niigata 950-2181 (Japan); Hashimoto, K. [Department of Material Science and Technology, Faculty of Engineering, Niigata University, 8050, Ikarashi, 2-no-cho, Nishi-ku, Niigata 950-218 (Japan); Fujiki, K. [Department of Environmental Science, Niigata Institute of Technology, 1719, Fujihashi, Kashiwazaki, Niigata 945-1195 (Japan); Yamauchi, T. [Graduate School of Science and Technology, Niigata University, 8050, Ikarashi, 2-no-cho, Nishi-ku, Niigata 950-2181 (Japan); Department of Material Science and Technology, Faculty of Engineering, Niigata University, 8050, Ikarashi, 2-no-cho, Nishi-ku, Niigata 950-218 (Japan); Tsubokawa, N., E-mail: ntsuboka@eng.niigata-u.ac.jp [Graduate School of Science and Technology, Niigata University, 8050, Ikarashi, 2-no-cho, Nishi-ku, Niigata 950-2181 (Japan); Department of Material Science and Technology, Faculty of Engineering, Niigata University, 8050, Ikarashi, 2-no-cho, Nishi-ku, Niigata 950-218 (Japan)

2014-02-14

To improve the dispersibility of polycrystalline nanodiamond (ND) in solvents, the grafting of polymers and introduction of ionic groups onto ND surface via radical trapping by ND surface were investigated. The grafting of polyoxyethylene (POE) onto ND surface by trapping of POE radicals formed by the thermal decomposition of POE macro azo-initiator (Azo-POE) was examined. The polymer radicals formed by the thermal decomposition of Azo-POE were successfully trapped by ND surface to give POE-grafted ND. The effect of temperature on the grafting of POE onto ND was discussed. In addition, the introduction of cationic protonated amidine groups onto ND was achieved by the trapping of radicals bearing protonated amidine groups formed by thermal decomposition of 2,2′-azobis(2-methylpropionamidine)dihydrochloride (AMPA). The anionic carboxylate groups was introduced onto ND surface by the trapping of the radicals bearing carboxyl groups formed by thermal decomposition of 4,4′-azobis(4-cyonovaleric acid) (ACVA) followed by the treatment with NaOH aqueous solution. The dispersibility of ND in water was remarkably improved by the grafting of POE, based on the steric hindrance of polymer chains and by the introduction of ionic groups, based on the ionic repulsion, onto ND surface. - Highlights: • Grafting of PEG onto nanodiamond was achieved by radical trapping. • Introduction of ionic groups onto nanodiamond was achieved by radical trapping. • Nanodiamond was dispersed by PEG grafting based on steric hindrance of PEG chains. • Nanodiamond was dispersed by introduction of ionic groups based on ionic repulsion.

α-Oxo-Ketenimines from Isocyanides and α-Haloketones: Synthesis and Divergent Reactivity.

Science.gov (United States)

Mamboury, Mathias; Wang, Qian; Zhu, Jieping

2017-09-18

The palladium-catalyzed reaction of α-haloketones with isocyanides afforded α-oxo-ketenimines through β-hydride elimination of the β-oxo-imidoyl palladium intermediates. Reaction of these relatively stable α-oxo-ketenimines with nucleophiles such as hydrazines, hydrazoic acid, amines, and Grignard reagent afforded pyrazoles, tetrazole, β-keto amidines, and enaminone, respectively, with high chemoselectivity. Whereas amines attack exclusively on the ketenimine functions, the formal [3+2] cycloaddition between N-monosubstituted hydrazines and α-oxo-ketenimines was initiated by nucleophilic addition to the carbonyl group. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Peptidylarginine deiminases: novel drug targets for prevention of neuronal damage following hypoxic ischemic insult (HI) in neonates.

Science.gov (United States)

Lange, Sigrun; Rocha-Ferreira, Eridan; Thei, Laura; Mawjee, Priyanka; Bennett, Kate; Thompson, Paul R; Subramanian, Venkataraman; Nicholas, Anthony P; Peebles, Donald; Hristova, Mariya; Raivich, Gennadij

2014-08-01

Neonatal hypoxic ischaemic (HI) injury frequently causes neural impairment in surviving infants. Our knowledge of the underlying molecular mechanisms is still limited. Protein deimination is a post-translational modification caused by Ca(+2) -regulated peptidylarginine deiminases (PADs), a group of five isozymes that display tissue-specific expression and different preference for target proteins. Protein deimination results in altered protein conformation and function of target proteins, and is associated with neurodegenerative diseases, gene regulation and autoimmunity. In this study, we used the neonatal HI and HI/infection [lipopolysaccharide (LPS) stimulation] murine models to investigate changes in protein deimination. Brains showed increases in deiminated proteins, cell death, activated microglia and neuronal loss in affected brain areas at 48 h after hypoxic ischaemic insult. Upon treatment with the pan-PAD inhibitor Cl-amidine, a significant reduction was seen in microglial activation, cell death and infarct size compared with control saline or LPS-treated animals. Deimination of histone 3, a target protein of the PAD4 isozyme, was increased in hippocampus and cortex specifically upon LPS stimulation and markedly reduced following Cl-amidine treatment. Here, we demonstrate a novel role for PAD enzymes in neural impairment in neonatal HI Encephalopathy, highlighting their role as promising new candidates for drug-directed intervention in neurotrauma. Hypoxic Ischaemic Insult (HI) results in activation of peptidylarginine deiminases (PADs) because of calcium dysregulation. Target proteins undergo irreversible changes of protein bound arginine to citrulline, resulting in protein misfolding. Infection in synergy with HI causes up-regulation of TNFα, nuclear translocation of PAD4 and change in gene regulation as a result of histone deimination. Pharmacological PAD inhibition significantly reduced HI brain damage. © 2014 The Authors. Journal of Neurochemistry

Electrochemical and calorimetric investigation of interaction of novel biscationic anticancer agents with DNA; Investigacao eletroquimica e calorimetrica da interacao de novos agentes antitumorais biscationicos com DNA

Energy Technology Data Exchange (ETDEWEB)

Silva, Lauris Lucia da; Donnici, Claudio Luis; Lopes, Julio Cesar Dias, E-mail: cdonnici@terra.com.br [Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil). Inst. de Ciencias Exatas. Dept. de Quimica; Goulart, Marilia Oliveira Fonseca; Abreu, Fabiane Caxico de; Paula, Francine Santos de [Universidade Federal de Alagoas (UFAL), Maceio, AL (Brazil). Campus A.C. Simoes. Inst. de Quimica e Biotecnologia; Bravo, Carlos E. Salas; Santoro, Marcelo Matos [Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil). Dept. de Bioquimica e Imunologia; Denadai, Angelo Marcio Leite [Centro Federal de Educacao Tecnologica, Timoteo, MG (Brazil). Campus VII; Santos, Alexandre Martins Costa [Universidade Federal do Espirito Santo, Vitoria, ES (Brazil). Dept. de Ciencias Fisiologicas; Montanari, Carlos Alberto [Universidade de Sao Paulo, Sao Carlos, SP (Brazil). Inst. de Quimica

2012-07-01

Biscationic amidines bind in the DNA minor groove and present biological activity against a range of infectious diseases. Two new biscationic compounds (bis-{alpha}-{omega}-S-thioureido, amino and sulfide analogues) were synthesized in good yields and fully characterized, and their interaction with DNA was also investigated. Isothermal titration calorimetry (ITC) was used to measure the thermodynamic properties of binding interactions between DNA and these ligands. A double stranded calf thymus DNA immobilized on an electrode surface was used to study the possible DNA-interacting abilities of these compounds towards dsDNA in situ. A remarkable interaction of these compounds with DNA was demonstrated and their potential application as anticancer agents was furthered. (author)

Synthesis and Spectral Analysis of 3,4,5-trichloro-6-(dibenzo[d,f][1,3]diazepin-5-yl-[1,2]-benzoquinones

Directory of Open Access Journals (Sweden)

Mohsen A. M. Gomaa

2011-01-01

Full Text Available Reaction of N1,N2-di-(4-methoxyphenyl- or N1,N2-di-(4-hydroxyphenyl -amidines (1a-d with 3,4,5,6-tetrachloro-1,2-benzoquinone (2 in ethyl acetate at room temperature led to formation of new 3,4,5-trichloro-6-(2-hydroxy-6-methyldibenzo[d,f][1,3]diazepin-5-yl[1,2]-benzoquinones (3a-d in addition to N-aryl-N'-(6,7,8,9-tetrachloro-4-hydroxydibenzo-[1,4]dioxin-2-ylacetamidines (4a,b. The rational of formation of products 3a-d and 4a,b was discussed and structures were confirmed on the basis of elemental analysis and spectral data.

Zolpidem, A Clinical Hypnotic that Affects Electronic Transfer, Alters Synaptic Activity Through Potential Gaba Receptors in the Nervous System Without Significant Free Radical Generation

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Peter Kovacic

2009-01-01

Full Text Available Zolpidem (trade name Ambien has attracted much interest as a sleep-inducing agent and also in research. Attention has been centered mainly on receptor binding and electrochemistry in the central nervous system which are briefly addressed herein. A novel integrated approach to mode of action is presented. The pathways to be discussed involve basicity, reduction potential, electrostatics, cell signaling, GABA receptor binding, electron transfer (ET, pharmacodynamics, structure activity relationships (SAR and side effects. The highly conjugated pyridinium salt formed by protonation of the amidine moiety is proposed to be the active form acting as an ET agent. Extrapolation of reduction potentials for related compounds supports the premise that zolpidem may act as an ET species in vivo. From recent literature reports, electrostatics is believed to play a significant role in drug action.

A straightforward and efficient synthesis of 3-(pyrimidinyl)propanoates from levulinic acid

International Nuclear Information System (INIS)

Flores, Alex F.C.; Malavolta, Juliana L.; Souto, Alynne A.; Goularte, Rayane B.; Flores, Darlene C.

2013-01-01

The cyclocondensation of methyl 7,7,7-trifluoro-4-methoxy-6-oxo-4-heptenoate and methyl 7,7,7-trichloro-4-methoxy-6-oxo-4-heptenoate, derived from levulinic acid with amidines [NH 2 CONH 2 , NH 2 CR(NH) (R = H, Me, Ph, NH 2 , SMe and 1H-pyrazol-1-yl), 5-amino-3-methyl-1H-pyrazol and 2-aminothiazole] into pyrimidine and pyrimidine-like derivatives as a new type of glutamate-like 3-(trihalomethylatedpyrimidinyl)propanoate is reported. Preparation of 3-(trihalomethylatedpyrimidinyl) propanohydrazides is also described. The synthetic potential of this straightforward protocol was established by the synthesis of fourteen new 3-(pyrimidinyl) propanoates in regular to good yields (38-92%). The structural assignments were based on the analysis of their 1 H and 13 C nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS) data. (author)

Synthesis and reactions with a midines of derivates cycles and of open chain of 2-bromo-3, 4-dioxobutanoic; Sintesis y reacciones con amidinas de derivados ciclicos y de cadena abierta del acido 2-bromo-3, 4-dioxobutanoico

Energy Technology Data Exchange (ETDEWEB)

Ancos, B. de; Delgado, F.; Martin, M.R. [Departamento de Quimica Organica, Facultad de Ciencias, Universidad Autonoma, Madrid (Spain)

1995-12-31

Bromination of enaminoesters 1 and 5, in appropriate conditions, affords in good yield enamines of the corresponding 2-bromo-3.4-dioxobutanoic acid derivatives 2-3 and 6 or dibromocompounds 4 and 6. The open chain enaminoesters (1-3) are more easily hydrolyzed that enaminofuranones 5 and 6. Prolongated treatment of 6 with hydrochloric acid affords the chlorinated enamine 11. The synthesis of 3-Bromo-4-hydroxy-5-methoxyfuran-2(5H)-one 10 can be achieved by bromination of 12, obtained by hydrolysis of 5. The reaction of methyl 3-bromo-4, 4-dimethoxy-3-oxobutanoate with amidines is a good method for the synthesis of 5-bromo-6-(dimethoxymethyl) pyrimidine-4(3H)-ones substituted at 2 position. Under the same conditions the reaction of furanone 10 with benzamide does not lead to the corresponding imidazoline. (Author) 12 refs.

Recent advances in the ruthenium(ii)-catalyzed chelation-assisted C-H olefination of substituted aromatics, alkenes and heteroaromatics with alkenes via the deprotonation pathway.

Science.gov (United States)

Manikandan, Rajendran; Jeganmohan, Masilamani

2017-08-08

The transition-metal-catalyzed chelation-assisted alkenylation at the inert C-H bond of aromatics with alkenes is one of the efficient methods to synthesize substituted vinylarenes in a highly regio- and stereoselective manner. Palladium, rhodium and ruthenium complexes are frequently used as catalysts for this type of transformation. The present review describes the recent advances in the ruthenium-catalyzed chelation-assisted alkenylation at the C-H bond of aromatics, alkenes and heteroaromatics with alkenes via the deprotonation pathway. Several directing groups including 2-pyridyl, carbonyl, amidine, amide, amine, imidate, sulphonic acid, triazole, cyano, oxazolidinone and hydontoin are widely used in the reaction. The scope, limitation and mechanistic investigation of the alkenylation reactions are discussed elaborately. This feature article includes all the reported ruthenium-catalyzed alkenylation reactions via the deprotonation pathway until the end of March 2017.

Hydrogen--deuterium exchanges in nucleosides and nucleotides. A mechanism for exchange of the exocyclic amino hydrogens of adenosine

International Nuclear Information System (INIS)

Cross, D.G.; Brown, A.; Fisher, H.F.

1975-01-01

The pH dependence of the apparent first-order rate constant for the exchange of the exocyclic amino hydrogens of adenosine with deuterium from the solvent was measured by stopped-flow ultraviolet spectroscopy. This dependence shows acid catalysis, base catalysis, and spontaneous exchange at neutral pH values. A study of the effect of several buffers on the rates of exchange reveals both general acid and general base catalytic behavior for the exchange process. We propose a general mechanism for the exchange which requires N-1 protonated adenosine as an intermediate for the acid-catalyzed exchange and amidine anion for the base-catalyzed exchange. In both cases the rate-limiting step is the base-catalyzed abstraction of a proton from the exocyclic amino moiety. Evaluation of the rate constants predicts the equilibrium for the exocyclic amino/imino tautomers to be 6.3 x 10 3 :1. (U.S.)

A straightforward and efficient synthesis of 3-(pyrimidinyl)propanoates from levulinic acid

Energy Technology Data Exchange (ETDEWEB)

Flores, Alex F.C.; Malavolta, Juliana L.; Souto, Alynne A.; Goularte, Rayane B.; Flores, Darlene C., E-mail: alex.fcf@ufsm.br [Universidade Federal de Santa Maria (UFSM/NUQUIMHE), RS (Brazil). Departamento de Quimica. Nucleo de Quimica de Heterociclos

2013-04-15

The cyclocondensation of methyl 7,7,7-trifluoro-4-methoxy-6-oxo-4-heptenoate and methyl 7,7,7-trichloro-4-methoxy-6-oxo-4-heptenoate, derived from levulinic acid with amidines [NH{sub 2}CONH{sub 2}, NH{sub 2}CR(NH) (R = H, Me, Ph, NH{sub 2}, SMe and 1H-pyrazol-1-yl), 5-amino-3-methyl-1H-pyrazol and 2-aminothiazole] into pyrimidine and pyrimidine-like derivatives as a new type of glutamate-like 3-(trihalomethylatedpyrimidinyl)propanoate is reported. Preparation of 3-(trihalomethylatedpyrimidinyl) propanohydrazides is also described. The synthetic potential of this straightforward protocol was established by the synthesis of fourteen new 3-(pyrimidinyl) propanoates in regular to good yields (38-92%). The structural assignments were based on the analysis of their {sup 1}H and {sup 13}C nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS) data. (author)

Recent Advances in the Synthesis and Anticancer Activity of Some Molecules Other Than Nitrogen Containing Heterocyclic Moeities.

Science.gov (United States)

Akhtar, Md Jawaid; Yar, M Shahar; Khan, Ahsan Ahmed; Ali, Zulphikar; Haider, Md Rafi

2017-01-01

The present review article presented a detailed account of the design strategies and the structure activity relationship of different derivatives apart from the nitrogen containing ring. These scaffolds play an important part in the drug discovery which showed anticancer activity against different human cancer cell lines through apoptosis, cell cycle arrest, inhibiting kinases, angiogenesis, disruption of cell migration, modulation of nuclear receptor responsiveness and others. Naphthalenes amides/amidines, furan, podophyllotoxin, platinum compounds, steroids, and urea, which forms the core part or along with other N-heterocyclic rings are enclosed. Some of these compounds e.g. podophyllotoxin and platinum based drugs displayed anticancer activity at nanomolar range. Various substitutions from the earlier and latest information are prerequisite in the drug synthesis process. The review focused on the recent development of these derivatives, design and anticancer properties, thus providing with the most profound knowledge for the development of targeted based anticancer drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Studies on 2-Arylhydrazononitriles: Synthesis of 3-Aryl-2-arylhydrazopropanenitriles and Their Utility as Precursors to 2-Substituted Indoles, 2-Substituted-1,2,3-Triazoles, and 1-Substituted Pyrazolo[4,3-d]pyrimidines

Directory of Open Access Journals (Sweden)

Khaled D. Khalil

2012-10-01

Full Text Available Coupling of 2-benzylmalononitrile with aromatic diazonium salts afforded 3-phenyl-2-arylhydrazonopropanenitriles 4a,b, which were rearranged into 2-cyanoindoles 5a,b upon heating with ZnCl2 in the presence of glacial acetic acid. The produced indole derivatives 5a,b can be successfully used as valuable precursors to synthesize 1,2,4-oxadiazolylindoles 8a,b. The reaction of arylhydrazononitriles 4a,b with hydroxylamine afforded an amidoximes 9a,b that could be cyclized into 1,2,3-triazole-4-amines 10a,b. In addition, 4a,b could be converted into 4-aminopyrazoles 12a,b via condensation with chloroacetonitrile in the presence of triethylamine as a basic catalyst. Finally, compounds 12a,b were refluxed with dimethylformamide dimethylacetal (DMFDMA to afford amidines 13a,b that were readily cyclized to the corresponding pyrazolo[4,3-d]pyrimidines 14a,b when refluxed with ammonium acetate.

An improved synthesis of α-13C glycine and heteronuclear NMR studies of its incorporation into thioredoxin

International Nuclear Information System (INIS)

Wishart, D.S.; Sykes, B.D.; Richards, F.M.

1992-01-01

We present an improved method to easily prepare gram quantities of α- 13 C glycine beginning from K 13 CN. The four step synthesis involves the production of an N, N-diphenyl-cyanoformamidine intermediate through the coupling of cyanide to N, N-diphenylcarbodiimide. Subsequent reduction by LiAlH 4 and hydrolysis of the resulting amidine produces fully enriched α- 13 C labelled glycine with a 45-50% yield. This relatively fast and simple synthesis uses only commonly available compounds and requires no special equipment, making the process easy to perform in any well equipped biochemistry laboratory. We further demonstrate that the product may be used, without extensive purification, to specifically label bacterially expressed proteins (E. coli thioredoxin) through standard biosynthetic procedures. We also show that the 13 C glycine-labelled protein may be readily analyzed using commonly available heteronuclear NMR techniques. Complete assignments for all 9 glycines of native E. coli thoredoxin are presented. (Author)

The Uses of 2-Ethoxy-(4H-3,1-benzoxazin-4-one in the Synthesis of Some Quinazolinone Derivatives of Antimicrobial Activity

Directory of Open Access Journals (Sweden)

Fakhry A. El-Bassiouny

2011-07-01

Full Text Available The behavior of 2-ethoxy-(4H-3,1-benzoxazin-4-one (1 towards nitrogen nucleo-philes, e.g. ethanolamine, aromatic amines (namely: p-toluidine, p-anisidine, p-hydroxyaniline, o-hydroxyaniline, o-bromoaniline, o-phenylenediamine, p-phenylene- diamine, o-tolidinediamine p-aminobenzoic acid, glucosamine hydrochloride,  2-amino- nicotinic acid, 1-naphthalenesulfonic acid hydrazide, n-decanoic acid hydrazide, benzoic acid hydrazide, semicarbazide, aminoacids (e.g. D,L-alanine, L-asparagine, L-arginine and derivatives of 2-aminothiodiazole has been investigated. The behavior of the benzoxazinone towards a selected sulfur nucleophile, L-cysteine, has also been discussed. Formation of an amidine salt as a reaction intermediate has been assumed. The effect of solvent in some reactions has been elucidated. The structures of all the novel quinazoline and quinazolinone derivatives, obtained by heterocyclic ring opening and ring closure were inferred by the IR, MS as well as 1H-NMR spectral analysis. Moreover, the antimicrobial potential of some of the new synthesized derivatives has been evaluated.

Poly[mu2-(N-hydroxypyridine-2-carboxamidine)-mu2-nitrato-silver(I)].

Science.gov (United States)

Cui, Ai-Li; Han, Peng; Yang, Hui-Juan; Wang, Ru-Ji; Kou, Hui-Zhong

2007-12-01

In the title complex, [Ag(NO3)(C6H7N3O)]n or [Ag(NO3)(pyaoxH2)] (pyaoxH2 is N-hydroxypyridine-2-carboxamidine), the Ag+ ion is bridged by the pyaoxH2 ligands and nitrate anions, giving rise to a two-dimensional molecular structure. Each pyaoxH2 ligand coordinates to two Ag+ ions using its pyridyl and carboxamidine N atoms, and the OH and the NH2 groups are uncoordinated. Each nitrate anion uses two O atoms to coordinate to two Ag+ ions. The Ag...Ag separation via the pyaoxH2 bridge is 2.869 (1) A, markedly shorter than that of 6.452 (1) A via the nitrate bridge. The two-dimensional structure is fishscale-like, and can be described as pyaoxH2-bridged Ag2 nodes that are further linked by nitrate anions. Hydrogen bonding between the amidine groups and the nitrate O atoms connects adjacent layers into a three-dimensional network.

Interactions between similar and dissimilar charged interfaces in the presence of multivalent anions.

Science.gov (United States)

Moazzami-Gudarzi, Mohsen; Adam, Pavel; Smith, Alexander M; Trefalt, Gregor; Szilágyi, István; Maroni, Plinio; Borkovec, Michal

2018-04-04

Direct force measurements involving amidine latex (AL) and sulfate latex (SL) particles in aqueous solutions containing multivalent ferrocyanide anions are presented. These measurements feature three different pairs of particles, namely SL-SL, AL-SL, and AL-AL. The force profiles are quantitatively interpreted in terms of the theory by Derjaguin, Landau, Verwey, and Overbeek (DLVO) that is combined with a short-ranged exponential attraction. In monovalent salt solutions, the AL particles are positively charged, while the SL particles are negatively charged. In solutions containing ferrocyanide, the charge of the AL particles is reversed as the concentration is increased. The longer-ranged component of all force profiles is fully compatible with DLVO theory, provided effects of charge regulation are included. At shorter distances, an additional exponential attraction must be introduced, whereby the respective decay length is about 2 nm for the AL-AL pair, and below 1 nm for the SL-SL pair. This non-DLVO force is intermediate for the asymmetric AL-SL pair. These additional forces are probably related to charge fluctuations, patch-charged interactions, or hydrophobic forces.

The first proton sponge-based amino acids: synthesis, acid-base properties and some reactivity.

Science.gov (United States)

Ozeryanskii, Valery A; Gorbacheva, Anastasia Yu; Pozharskii, Alexander F; Vlasenko, Marina P; Tereznikov, Alexander Yu; Chernov'yants, Margarita S

2015-08-21

The first hybrid base constructed from 1,8-bis(dimethylamino)naphthalene (proton sponge or DMAN) and glycine, N-methyl-N-(8-dimethylamino-1-naphthyl)aminoacetic acid, was synthesised in high yield and its hydrobromide was structurally characterised and used to determine the acid-base properties via potentiometric titration. It was found that the basic strength of the DMAN-glycine base (pKa = 11.57, H2O) is on the level of amidine amino acids like arginine and creatine and its structure, zwitterionic vs. neutral, based on the spectroscopic (IR, NMR, mass) and theoretical (DFT) approaches has a strong preference to the zwitterionic form. Unlike glycine, the DMAN-glycine zwitterion is N-chiral and is hydrolytically cleaved with the loss of glycolic acid on heating in DMSO. This reaction together with the mild decarboxylative conversion of proton sponge-based amino acids into 2,3-dihydroperimidinium salts under air-oxygen was monitored with the help of the DMAN-alanine amino acid. The newly devised amino acids are unique as they combine fluorescence, strongly basic and redox-active properties.

Binding cooperativity between a ligand carbonyl group and a hydrophobic side chain can be enhanced by additional H-bonds in a distance dependent manner: A case study with thrombin inhibitors.

Science.gov (United States)

Said, Ahmed M; Hangauer, David G

2015-01-01

One of the underappreciated non-covalent binding factors, which can significantly affect ligand-protein binding affinity, is the cooperativity between ligand functional groups. Using four different series of thrombin inhibitors, we reveal a strong positive cooperativity between an H-bond accepting carbonyl functionality and the adjacent P3 hydrophobic side chain. Adding an H-bond donating amine adjacent to the P3 hydrophobic side chain further increases this positive cooperativity thereby improving the Ki by as much as 546-fold. In contrast, adding an amidine multiple H-bond/salt bridge group in the distal S1 pocket does not affect this cooperativity. An analysis of the crystallographic B-factors of the ligand groups inside the binding site indicates that the strong cooperativity is mainly due to a significant mutual reduction in the residual mobility of the hydrophobic side chain and the H-bonding functionalities that is absent when the separation distance is large. This type of cooperativity is important to encode in binding affinity prediction software, and to consider in SAR studies. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Klebsazolicin inhibits 70S ribosome by obstructing the peptide exit tunnel

Energy Technology Data Exchange (ETDEWEB)

Metelev, Mikhail; Osterman, Ilya A.; Ghilarov, Dmitry; Khabibullina, Nelli F.; Yakimov, Alexander; Shabalin, Konstantin; Utkina, Irina; Travin, Dmitry Y.; Komarova, Ekaterina S.; Serebryakova, Marina; Artamonova, Tatyana; Khodorkovskii, Mikhail; Konevega, Andrey L.; Sergiev, Petr V.; Severinov, Konstantin; Polikanov, Yury S.

2017-08-28

Whereas screening of the small-molecule metabolites produced by most cultivatable microorganisms often results in the rediscovery of known compounds, genome-mining programs allow researchers to harness much greater chemical diversity, and result in the discovery of new molecular scaffolds. Here we report the genome-guided identification of a new antibiotic, klebsazolicin (KLB), from Klebsiella pneumoniae that inhibits the growth of sensitive cells by targeting ribosomes. A ribosomally synthesized post-translationally modified peptide (RiPP), KLB is characterized by the presence of a unique N-terminal amidine ring that is essential for its activity. Biochemical in vitro studies indicate that KLB inhibits ribosomes by interfering with translation elongation. Structural analysis of the ribosome–KLB complex showed that the compound binds in the peptide exit tunnel overlapping with the binding sites of macrolides or streptogramin-B. KLB adopts a compact conformation and largely obstructs the tunnel. Engineered KLB fragments were observed to retain in vitro activity, and thus have the potential to serve as a starting point for the development of new bioactive compounds.

Integration of Bromine and Cyanogen Bromide Generators for the Continuous-Flow Synthesis of Cyclic Guanidines.

Science.gov (United States)

Glotz, Gabriel; Lebl, René; Dallinger, Doris; Kappe, C Oliver

2017-10-23

A continuous-flow process for the in situ on-demand generation of cyanogen bromide (BrCN) from bromine and potassium cyanide that makes use of membrane-separation technology is described. In order to circumvent the handling, storage, and transportation of elemental bromine, a continuous bromine generator using bromate-bromide synproportionation can optionally be attached upstream. Monitoring and quantification of BrCN generation was enabled through the implementation of in-line FTIR technology. With the Br 2 and BrCN generators connected in series, 0.2 mmol BrCN per minute was produced, which corresponds to a 0.8 m solution of BrCN in dichloromethane. The modular Br 2 /BrCN generator was employed for the synthesis of a diverse set of biologically relevant five- and six-membered cyclic amidines and guanidines. The set-up can either be operated in a fully integrated continuous format or, where reactive crystallization is beneficial, in semi-batch mode. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Aryliminopropadienone-C-Amidoketenimine- Amidinoketene-2-Aminoquinolone Cascades and the Ynamine-Isocyanate Reaction.

Science.gov (United States)

Wentrup, Curt; Rao, V. V. Ramana; Frank, Wilhelm; Fulloon, Belinda E.; Moloney, Daniel W. J.; Mosandl, Thomas

1999-05-14

Imidoylketenes 11 and oxoketenimines 12 are generated by flash vacuum thermolysis of Meldrum's acid derivatives 9, pyrrolediones 17 and 18, and triazole 19 and are observed by IR spectroscopy. Ketenimine-3-carboxylic acid esters 12a are isolable at room temperature. Ketenes 11 and ketenimines 12 undergo rapid interconversion in the gas phase, and the ketenes cyclize to 4-quinolones 13. When using an amine leaving group in Meldrum's acid derivatives 9c, the major reaction products are aryliminopropadienones, ArN=C=C=C=O (15). The latter react with 1 equiv of nucleophile to produce ketenimines 12 and with 2 equiv to afford malonic acid imide derivatives 16. N-Arylketenimine-C-carboxamides 12c cyclize to quinolones 13c via the transient amidinoketenes 11c at temperatures of 25-40 degrees C. This implies rapid interconversion of ketenes and ketenimines by a 1,3-shift of the dimethylamino group, even at room temperature. This interconversion explains previously poorly understood outcomes of the ynamine-isocyanate reaction. The solvent dependence of the tautomerism of 4-quinolones/4-quinolinols is discussed. Rotational barriers of NMe(2) groups in amidoketenimines 12c and malonioc amides and amidines 16 (24) are reported.

Synthesis and antibacterial evaluation of new, unsymmetrical triaryl bisamidine compounds

Science.gov (United States)

Nguyen, Son T.; Williams, John D.; Butler, Michelle M.; Ding, Xiaoyuan; Mills, Debra M.; Tashjian, Tommy F.; Panchal, Rekha G.; Weir, Susan K.; Moon, Chaeho; Kim, Hwa-Ok; Marsden, Jeremiah; Peet, Norton P.; Bowlin, Terry L.

2014-01-01

Herein we describe the synthesis and antibacterial evaluation of a new, unsymmetrical triaryl bisamidine compound series, [Am]-[indole]-[linker]-[HetAr/Ar]-[Am], in which [Am] is an amidine or amino group, [linker] is a benzene, thiophene or pyridine ring, and [HetAr/Ar] is a benzimidazole, imidazopyridine, benzofuran, benzothiophene, pyrimidine or benzene ring. When the [HetAr/Ar] unit is a 5,6-bicyclic heterocycle, it is oriented such that the 5-membered ring portion is connected to the [linker] unit and the 6-membered ring portion is connected to the [Am] unit. Among the 34 compounds in this series, compounds with benzofuran as the [HetAr/Ar] unit showed the highest potencies. Introduction of a fluorine atom or a methyl group to the triaryl core led to the more potent analogs. Bisamidines are more active toward bacteria while the monoamidines are more active toward mammalian cells (as indicated by low CC50 values). Importantly, we identified compound P12a (MBX 1887) with a relatively narrow spectrum against bacteria and a very high CC50 value. Compound P12a has been scaled up and is currently undergoing further evaluations for therapeutic applications. PMID:24969013

Effection of UV-LED Illuminant on the Curation of Photolatent-amidine Mixed with Bisphenol A Epoxy Acrylate under Printing Conditions

Directory of Open Access Journals (Sweden)

Duan Huawei

2016-01-01

Full Text Available In order to make photocuring ink or coating cured by UV-LED illuminant, we synthesized (4-((hexahydropyrrolo[1,2-a]pyrimidin-1 (2H-ylmethylphenyl(phenylmethanone(PL -DBN and (4-((octahydropyrimido[1,2-a]azepin-1(2H-ylmethylphenyl(phenylmet hanone(PL -DBU as photoinitiators. Different mass fraction of the photoinitiators was mixed with bisphenol A epoxy acrylate, cured by different wavelengths and power of UV-LED illuminant,and investigated the curing effects of photoinitiators on bisphenol A epoxy acrylate. The results show that the conversion of C=C double bonds of bisphenol A epoxy acrylate will increase as the mass fraction of the photoinitiators or the power of UV-LED illuminant increase. In the same conditions, the curing effect of using 365nm UV-LED illuminant on bisphenol A epoxy acrylate is better than using 395nm UV-LED illuminant. PL-DBU has a better curing effect on the bisphenol A epoxy acrylate rather than PL-DBN. When using the 8W/cm2 of 365nm UV-LED illuminant to cure a mixture of 3% PL-DBU and 97% bisphenol A epoxy acrylate, it will be dry completely in 2 seconds, moreover, the conversion reach 79%.

S-adenosylmethionine decarboxylase inhibitors: new aryl and heteroaryl analogues of methylglyoxal bis(guanylhydrazone).

Science.gov (United States)

Stanek, J; Caravatti, G; Capraro, H G; Furet, P; Mett, H; Schneider, P; Regenass, U

1993-01-08

A series of 3-acylbenzamidine (amidino)hydrazones 7a-h, the corresponding (hetero)aromatic congeners 7i-p, and 3,3'-bis-amidino-biaryls 25a-e were synthesized. The hydrazones 7a-p were prepared by conversion of the corresponding acyl nitriles 1a,c-d,i,n-p to the imido esters 3a,c-d,i and the amidines 5a,c-d,h-i, followed by a reaction with aminoguanidine, or vice versa. Similarly, the biaryl 3,3'-dinitriles 23a-e were converted, via the imino esters 24a-c or the imino thioesters 27d-e, to the diamidines 25a-e. These new products are conformationally constrained analogues of methylglyoxal bis(guanylhydrazone) (MGBG). They are up to 100 times more potent as inhibitors of rat liver S-adenosylmethionine decarboxylase (SMDC) and generally less potent inhibitors of rat small intestine diamine oxidase (DAO) than MGBG. Some of these SAMDC inhibitors, e.g., compounds 7a, 7e, 7i, 25a, and 25d, have shown antiproliferative effects against T24 human bladder carcinoma cells. These products, whose structure-activity relationships are discussed, are of interest as potential anticancer agents and drugs for the treatment of protozoal and Pneumocystis carinii infections.

Reaction of electron-transfer flavoprotein with electron-transfer flavoprotein-ubiquinone oxidoreductase

International Nuclear Information System (INIS)

Beckmann, J.D.; Frerman, F.E.

1985-01-01

The oxidative half-reaction of electron-transfer flavoprotein (ETF), electron transfer from ETF to electron-transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO), is dependent on complementary surface charges on the two proteins. ETF is the positively charged member of the redox pair. The evidence is based on the pH and ionic strength dependencies of the comproportionation of oxidized ETF and ETF hydroquinone catalyzed by ETF-QO and on the effects of chemical modification of ETF on the comproportionation reaction. Acetylation of one and five epsilon-amino groups of lysyl residues results in 3- and 13-fold increases, respectively, in the K/sub m/ of ETF-QO for ETF but no change in V/sub max/. Amidination, which maintains positive charge at modified loci, has no effect on steady-state kinetic constants. These chemical modifications have no effect on the equilibrium constant for equilibration of ETF redox states. The K/sub m/ of ETF-QO for ETF is pH dependent above pH 8.5, suggesting titration of lysyl residues. The ionic strength dependence of TN/KmETF for the reaction follows the limiting Bronsted equation. The ETF-QO-catalyzed comproportionation reaction exhibits a primary deuterium isotope effect in D 2 O, perhaps indicating the participation of solvent water in the electron-transfer reaction

Discovery of imidazopyridines containing isoindoline-1,3-dione framework as a new class of BACE1 inhibitors: Design, synthesis and SAR analysis.

Science.gov (United States)

Azimi, Sara; Zonouzi, Afsaneh; Firuzi, Omidreza; Iraji, Aida; Saeedi, Mina; Mahdavi, Mohammad; Edraki, Najmeh

2017-09-29

Alzheimer's disease is characterized by chronic neurodegeneration leading to dementia. The main cause of neurodegeneration is considered to be the accumulation of amyloid-β. Inhibiting BACE1 is a well-studied approach to lower the burden of amyloid-β aggregates. We designed a series of imidazopyridines-based compounds bearing phthalimide moieties as inhibitors of BACE1. The compounds 8a-o were synthesized by the Groebke-Blackburn-Bienaymé three-component reaction of heteroaromatic amidines, aldehydes and isocyanides. Evaluating the BACE1 inhibitory effects of the synthesized compounds revealed that introducing an aminocyclohexyl moiety in the imidazopyridine core resulted in a significant improvement in its BACE1 inhibitory potential. In this regard, compound 8e was the most potent against BACE1 with an IC 50 value of 2.84 (±0.95) μM. Molecular docking revealed that the nitrogen atom of imidazopyridines and the oxygen atom of the phenoxypropyl linker were involved in hydrogen bound interactions with Asp228 and Asp32 of BACE1 active site, respectively. The phthalimide moiety oriented toward the flap pocket and interacted with phe108, lle110, Trp115, Ile118 through van der Waal's and hydrophobic interactions. These findings demonstrate that imidazopyridines-based compounds bearing phthalimide moiety have the potential to decrease amyloid-β levels and ameliorate the symptoms of Alzheimer's disease. Copyright © 2017. Published by Elsevier Masson SAS.

Chemical composition and acaricide activity of an essential oil from a rare chemotype of Cinnamomum verum Presl on Rhipicephalus microplus (Acari: Ixodidae).

Science.gov (United States)

Monteiro, Ildenice Nogueira; Monteiro, Odair Dos Santos; Costa-Junior, Lívio Martins; da Silva Lima, Aldilene; Andrade, Eloisa Helena de Aguiar; Maia, José Guilherme Soares; Mouchrek Filho, Victor Elias

2017-04-30

The Essential Oils (EOs) from the leaves of species Cinnamomum verum J. Presl are used in the pharmaceutical industry for their numerous biological activities. Currently, the main compound of C. verum EO is eugenol which has acaricidal activity; however, a rare chemotype with benzyl benzoate as the main component can be found. Benzyl benzoate is recognized as an acaricide; however, studies of the C. verum EOs benzyl benzoate chemotype on Rhipicephalus microplus were not reported. The aim of this study was to evaluate the acaricide activity of an EO from a rare chemotype of C. verum, as well as purified benzyl benzoate, against larvae and engorged females of R. microplus resistant to amidines and pyrethroids. The EO was extracted from C. verum leaves and the compounds present were identified using a gas phase chromatograph coupled to a mass spectrometer. Efficacy against R. microplus was assessed by the larval packet and the engorged female immersion tests. A rare chemotype of C. verum was found to produce EOs with benzyl benzoate (65.4%) as the main compound. The C. verum essential oil was 3.3 times more efficient on the R. microplus larvae than was benzyl benzoate. However, no differences were found on the R. microplus engorged females. This is the first report regarding the acaricidal activity of C. verum with chemotype benzyl benzoate, and this compound showed acaricidal activity on R. microplus larvae. Copyright © 2017 Elsevier B.V. All rights reserved.

NETosis Delays Diabetic Wound Healing in Mice and Humans.

Science.gov (United States)

Fadini, Gian Paolo; Menegazzo, Lisa; Rigato, Mauro; Scattolini, Valentina; Poncina, Nicol; Bruttocao, Andrea; Ciciliot, Stefano; Mammano, Fabio; Ciubotaru, Catalin Dacian; Brocco, Enrico; Marescotti, Maria Cristina; Cappellari, Roberta; Arrigoni, Giorgio; Millioni, Renato; Vigili de Kreutzenberg, Saula; Albiero, Mattia; Avogaro, Angelo

2016-04-01

Upon activation, neutrophils undergo histone citrullination by protein arginine deiminase (PAD)4, exocytosis of chromatin and enzymes as neutrophil extracellular traps (NETs), and death. In diabetes, neutrophils are primed to release NETs and die by NETosis. Although this process is a defense against infection, NETosis can damage tissue. Therefore, we examined the effect of NETosis on the healing of diabetic foot ulcers (DFUs). Using proteomics, we found that NET components were enriched in nonhealing human DFUs. In an independent validation cohort, a high concentration of neutrophil elastase in the wound was associated with infection and a subsequent worsening of the ulcer. NET components (elastase, histones, neutrophil gelatinase-associated lipocalin, and proteinase-3) were elevated in the blood of patients with DFUs. Circulating elastase and proteinase-3 were associated with infection, and serum elastase predicted delayed healing. Neutrophils isolated from the blood of DFU patients showed an increased spontaneous NETosis but an impaired inducible NETosis. In mice, skin PAD4 activity was increased by diabetes, and FACS detection of histone citrullination, together with intravital microscopy, showed that NETosis occurred in the bed of excisional wounds. PAD4 inhibition by Cl-amidine reduced NETting neutrophils and rescued wound healing in diabetic mice. Cumulatively, these data suggest that NETosis delays DFU healing. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Replacement of a thiourea with an amidine group in a monofunctional platinum-acridine antitumor agent. Effect on DNA interactions, DNA adduct recognition and repair

Czech Academy of Sciences Publication Activity Database

Kostrhunová, Hana; Malina, Jaroslav; Pickard, A.J.; Štěpánková, Jana; Vojtíšková, Marie; Kašpárková, Jana; Muchová, T.; Rohlfing, M.L.; Bierbach, U.; Brabec, Viktor

2011-01-01

Roč. 8, č. 5 (2011), s. 1941-1954 ISSN 1543-8384 R&D Projects: GA ČR(CZ) GAP205/11/0856 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : platinum * DNA binding * anticancer effects Subject RIV: BO - Biophysics Impact factor: 4.782, year: 2011

Synthesis and structure-activity relationships of a series of increasingly hydrophobic cationic steroid lipofection reagents.

Science.gov (United States)

Gruneich, Jeffrey A; Diamond, Scott L

2007-05-01

The use of cholesterol-based cationic lipids and the ability of glucocorticoids to reduce local inflammatory response to lipoplexes motivated an investigation of structure-activity relationships for cationic steroids. A one-step synthetic scheme using iminothiolane was developed to link spermine to the 21-OH position of steroids via an amidine linkage. Five steroids (cortisol, dexamethasone, corticosterone, 11-deoxycortisol, and 11-deoxycorticosterone) with increasing hydrophobicity of the parent steroid (Log P(ster) from 1.51 to 3.01) were conjugated with spermine, formulated with dioleoylphosphatidylethanolamine (DOPE) at DOPE : steroid mole ratios (R) of R = 0.5 to 2, and then complexed with 1 microg enhanced green fluorescent protein (EGFP) plasmid DNA at charge ratios (CR) = 2 to 24 amines per phosphate (0.5 to 6 steroids per phosphate). The resulting 105 different formulations of the cationic steroid series were used to lipofect bovine aortic endothelial cells. Transgene expression data at either 24 or 48 h post-lipofection for all formulations was collapsed onto master curves when plotted against a single empirical dimensionless parameter, the lipofection index (LI) = CR (Log P(liposome))(Log P(ster)/|DeltaLog P|) [R/(R + 1)] where DeltaLog P = Log P(DOPE)- Log P(ster) and Log P(liposome) is a mole-weighted average of the DOPE/cationic steroid liposome hydrophobicity. For 7 lipofection increased linearly with LI (EGFP approximately 0 for LI 29, thus providing a predictive design rule based on Log P of the hydrophobic moiety of the cationic steroid lipid. Copyright (c) 2007 John Wiley & Sons, Ltd.

Synthesis of metal-fluoride nanoparticles supported on thermally reduced graphite oxide

Directory of Open Access Journals (Sweden)

Alexa Schmitz

2017-11-01

Full Text Available Metal-fluoride nanoparticles, (MFx-NPs with M = Fe, Co, Pr, Eu, supported on different types of thermally reduced graphite oxide (TRGO were obtained by microwave-assisted thermal decomposition of transition-metal amidinates, (M{MeC[N(iPr]2}n or [M(AMDn] with M = Fe(II, Co(II, Pr(III, and tris(2,2,6,6-tetramethyl-3,5-heptanedionatoeuropium, Eu(dpm3, in the presence of TRGO in the ionic liquid (IL 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIm][BF4]. The crystalline phases of the metal fluorides synthesized in [BMIm][BF4] were identified by powder X-ray diffraction (PXRD to be MF2 for M = Fe, Co and MF3 for M = Eu, Pr. The diameters and size distributions of MFx@TRGO were from (6 ± 2 to (102 ± 41 nm. Energy-dispersive X-ray spectroscopy (EDX and X-ray photoelectron spectroscopy (XPS were used for further characterization of the MFx-NPs. Electrochemical investigations of the FeF2-NPs@TRGO as cathode material for lithium-ion batteries were evaluated by galvanostatic charge/discharge profiles. The results indicate that the FeF2-NPs@TRGO as cathode material can present a specific capacity of 500 mAh/g at a current density of 50 mA/g, including a significant interfacial charge storage contribution. The obtained nanomaterials show a good rate capacity as well (220 mAh/g and 130 mAh/g at a current density of 200 and 500 mA/g, respectively.

Synthesis and radiofluorination of putative NMDA receptor ligands

Energy Technology Data Exchange (ETDEWEB)

Kronenberg, U

2011-01-15

In the course of this work on the synthesis of radioligands for the NMDA receptor the authentic standards and labeling precursors of four compounds with an amidine structure was performed. Synthesis of the precursors followed reaction conditions given in the literature and was successful. The imidoesters used for the synthesis were obtained from their nitriles in a Pinner synthesis, while 2-hydroxybenzylamine was synthesized in a reduction of 2-hydroxybenzonitrile using borane as a reducing agent. After a coupling reaction of the amine and the imidoester in DMF using triethylamine as base the precursors were obtained in good yields and purified by crystallization from methanol. The cyclic standard compound was synthesized directly from 2-(bromomethyl)- benzonitrile and 2-hydroxybenzylamine in a ring closing reaction. Similar to the other precursors, crystallization from methanol produced a pure compound. The authentic standards were synthesized starting from salicylaldehyde. In a four step synthesis the desired ortho-fluoroethoxybenzylamine was obtained in good yield. Coupling of the amine with the respective imidoester or in the case of the cyclic compound 2-(bromomethyl)-benzonitrile gave the desired product which was then purified by column chromatography or by crystallization from ethanol and water. For the labeling procedure 1-bromo-2-[{sub 18}F]fluoroethane was synthesized following a previously published pathway starting from 1,2-dibromoethane. An alternative route of radiosynthesis for this prosthetic group was tested using ethyleneglycole- 1,2-ditosylate. The labeling reaction was performed on one of the precursors testing both DMF and DMSO as solvents and using NaOH as base. Yields of N-(2-fluoroethoxybenzyl)- cinnamamidine were about 78 % at 80 C after 30 minutes in DMSO. The desired product can now be synthesized in sufficient yields for in vitro and in vivo evaluation studies. Labeling on the cyclic precursor was attempted utilizing DMSO as solvent

Synthesis and radiofluorination of putative NMDA receptor ligands

International Nuclear Information System (INIS)

Kronenberg, U.

2011-01-01

In the course of this work on the synthesis of radioligands for the NMDA receptor the authentic standards and labeling precursors of four compounds with an amidine structure was performed. Synthesis of the precursors followed reaction conditions given in the literature and was successful. The imidoesters used for the synthesis were obtained from their nitriles in a Pinner synthesis, while 2-hydroxybenzylamine was synthesized in a reduction of 2-hydroxybenzonitrile using borane as a reducing agent. After a coupling reaction of the amine and the imidoester in DMF using triethylamine as base the precursors were obtained in good yields and purified by crystallization from methanol. The cyclic standard compound was synthesized directly from 2-(bromomethyl)- benzonitrile and 2-hydroxybenzylamine in a ring closing reaction. Similar to the other precursors, crystallization from methanol produced a pure compound. The authentic standards were synthesized starting from salicylaldehyde. In a four step synthesis the desired ortho-fluoroethoxybenzylamine was obtained in good yield. Coupling of the amine with the respective imidoester or in the case of the cyclic compound 2-(bromomethyl)-benzonitrile gave the desired product which was then purified by column chromatography or by crystallization from ethanol and water. For the labeling procedure 1-bromo-2-[ 18 F]fluoroethane was synthesized following a previously published pathway starting from 1,2-dibromoethane. An alternative route of radiosynthesis for this prosthetic group was tested using ethyleneglycole- 1,2-ditosylate. The labeling reaction was performed on one of the precursors testing both DMF and DMSO as solvents and using NaOH as base. Yields of N-(2-fluoroethoxybenzyl)- cinnamamidine were about 78 % at 80 C after 30 minutes in DMSO. The desired product can now be synthesized in sufficient yields for in vitro and in vivo evaluation studies. Labeling on the cyclic precursor was attempted utilizing DMSO as solvent, but no

Radiosynthesis of (E)-N-(2-[{sup 11}C]methoxybenzyl)-3-phenyl-acrylamidine, a novel subnanomolar NR2B subtype-selective NMDA receptor antagonist

Energy Technology Data Exchange (ETDEWEB)

Thominiaux, Cyrille [Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, CEA/DSV, 4 place du General Leclerc, F-91401 Orsay (France); Bruin, Beatrice de [Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, CEA/DSV, 4 place du General Leclerc, F-91401 Orsay (France); Bramoulle, Yann [Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, CEA/DSV, 4 place du General Leclerc, F-91401 Orsay (France); Hinnen, Francoise [Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, CEA/DSV, 4 place du General Leclerc, F-91401 Orsay (France); Demphel, Stephane [Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, CEA/DSV, 4 place du General Leclerc, F-91401 Orsay (France); Valette, Heric [Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, CEA/DSV, 4 place du General Leclerc, F-91401 Orsay (France); Bottlaender, Michel [Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, CEA/DSV, 4 place du General Leclerc, F-91401 Orsay (France); Besret, Laurent [Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, CEA/DSV, 4 place du General Leclerc, F-91401 Orsay (France); Departement de Recherche Medicale, URA CEA/CNRS 2210, Service Hospitalier Frederic Joliot, CEA/DSV, 4 Place du General Leclerc, F-91401 Orsay (France); Kassiou, Michael [Department of PET and Nuclear Medicine, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050 (Australia); Department of Pharmacology, University of Sydney, NSW 2006 (Australia); Dolle, Frederic [Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, CEA/DSV, 4 place du General Leclerc, F-91401 Orsay (France)]. E-mail: frederic.dolle@cea.fr

2006-03-15

Recently, a novel series of amidines has been described, exhibiting high NR2B-subtype selective N-methyl-D-aspartate (NMDA) antagonist activity with nanomolar or subnanomolar affinity. Within the styrylamidine subclass (E)-N-(2-methoxybenzyl)-3-phenyl-acrylamidine (1), displayed the highest affinity (Ki=0.7nM versus [{sup 3}H]ifenprodil) and was considered an appropriate candidate for isotopic labelling with carbon-11 (T{sub 1/2}: 20.38min) at its methoxy group for imaging of NMDA receptors with PET. Derivative 1 has been labelled from the corresponding nor-analogue using [{sup 11}C]methyl triflate and the following experimental conditions : (1) trapping at -10{sup o}C of [{sup 11}C]methyl triflate in 300{mu}L of acetone containing 0.6-0.8mg of precursor 5 (2.4-3.2{mu}mol) and 5{mu}L of a 3M solution of NaOH in water (about 5eq.); (2) concentration to dryness of the reaction mixture (at 110{sup o}C, using a helium stream for 1-2min); (3) taking up the residue with 0.5mL of the HPLC mobile phase and (4) purification using semi-preparative HPLC (SymmetryPrep{sup (}R) C-18, Waters, 300x7.8mm). Typically, starting from a 1.5 Ci (55.5GBq) [{sup 11}C]CO{sub 2} production batch, 120-240m Ci (4.44-8.88GBq) of [{sup 11}C]-1 (20-40% decay-corrected radiochemical yield, n=5) was obtained within a total synthesis time of 25-30min. Specific radioactivities ranged from 0.8 to 1.2Ci/{mu}mol (29.6-44.4GBq/{mu}mol) at the end of radiosynthesis. No attempts were made to further optimise these reactions, as sufficient material was obtained to allow for preliminary pharmacological characterisation.

Tracers development for the PET study of nicotinic receptors: [11C]-mecamylamine and [11C]-SIB 1553A. Tritium and carbon-11 radiolabelling of a serine proteinase inhibitor: the t-PAstop

International Nuclear Information System (INIS)

Sobrio, F.

2002-12-01

In order to develop radiotracers for the Positron Emission Tomography (PET), we labelled both the mecamylamine and SIB-1553A with carbon-11 to study the nicotinic cholinergic receptors (nAChRs). The radiosynthesis of [ 11 C]-t-PA stop and the labelling with tritium of one analogue were realized for cerebral ischemia PET studies. The [ 11 C]-mecamylamine, a non-competitive and non-selective nAChRs antagonist was synthesized in 45 min via a N-[ 11 C]-methylation reaction. In the rat brain, the ex vivo studies showed no radio-metabolite 45 min after the injection of [ 11 C]-mecamylamine. The uptake kinetics in the rat brain or in vivo by PET in the anesthetized baboon or in the conscious monkey, reached a plateau around 45-50 min after injection. However, the saturation or displacement experiments did not permit to exhibit nor a significant difference of labelling between the different cerebral regions nor a specific uptake. In consequence, the [ 11 C]-mecamylamine was not an appropriate radioligand for nAChRs PET study. The labelling of [ 11 C]-SIB 1553A, a selective agonist for the nicotinic β4 subunit, required the synthesis in 5 steps (56% overall yield) of precursor for the incorporation of carbon-11. The radiosynthesis was performed in 36 min by a N-[ 11 C]-methylation reaction (yield: 75%). The [ 11 C]-t-PA stop was obtained from [ 11 C]-KCN with yields from 80 to 90%. For the first time with carbon-11, the formation of an amidine group was realized from a nitrile group. The labelling by isotopic exchange of hydrogen by tritium of the t-PA stop did not permit to obtain the [ 3 H]-t-PA stop but a tritiated analogue. This compound will be used to study its vectorization by micro-encapsulation. (author)

Selectivity in ligand binding to uranyl compounds: A synthetic, structural, thermodynamic and computational study

Energy Technology Data Exchange (ETDEWEB)

Arnold, John [Univ. of California, Berkeley, CA (United States)

2015-01-21

The uranyl cation (UO₂²⁺) is the most abundant form of uranium on the planet. It is estimated that 4.5 billion tons of uranium in this form exist in sea water. The ability to bind and extract the uranyl cation from aqueous solution while separating it from other elements would provide a limitless source of nuclear fuel. A large body of research concerns the selective recognition and extraction of uranyl. A stable molecule, the cation has a linear O=U=O geometry. The short U-O bonds (1.78 Å) arise from the combination of uranium 5f/6d and oxygen 2p orbitals. Due to the oxygen moieties being multiply bonded, these sites were not thought to be basic enough for Lewis acidic coordination to be a viable approach to sequestration. The goal of this research is thus to broaden the coordination chemistry of the uranyl ion by studying new ligand systems via synthetic, structural, thermodynamic and computational methods. It is anticipated that this fundamental science will find use beyond actinide separation technologies in areas such as nuclear waste remediation and nuclear materials. The focus of this study is to synthesize uranyl complexes incorporating amidinate and guanidinate ligands. Both synthetic and computational methods are used to investigate novel equatorial ligand coordination and how this affects the basicity of the oxo ligands. Such an understanding will later apply to designing ligands incorporating functionalities that can bind uranyl both equatorially and axially for highly selective sequestration. Efficient and durable chromatography supports for lanthanide separation will be generated by (1) identifying robust peptoid-based ligands capable of binding different lanthanides with variable affinities, and (2) developing practical synthetic methods for the attachment of these ligands to Dowex ion exchange resins.

Selectivity in ligand binding to uranyl compounds: A synthetic, structural, thermodynamic and computational study

International Nuclear Information System (INIS)

Arnold, John

2015-01-01

The uranyl cation (UO 2 2+ ) is the most abundant form of uranium on the planet. It is estimated that 4.5 billion tons of uranium in this form exist in sea water. The ability to bind and extract the uranyl cation from aqueous solution while separating it from other elements would provide a limitless source of nuclear fuel. A large body of research concerns the selective recognition and extraction of uranyl. A stable molecule, the cation has a linear O=U=O geometry. The short U-O bonds (1.78 Å) arise from the combination of uranium 5f/6d and oxygen 2p orbitals. Due to the oxygen moieties being multiply bonded, these sites were not thought to be basic enough for Lewis acidic coordination to be a viable approach to sequestration. The goal of this research is thus to broaden the coordination chemistry of the uranyl ion by studying new ligand systems via synthetic, structural, thermodynamic and computational methods. It is anticipated that this fundamental science will find use beyond actinide separation technologies in areas such as nuclear waste remediation and nuclear materials. The focus of this study is to synthesize uranyl complexes incorporating amidinate and guanidinate ligands. Both synthetic and computational methods are used to investigate novel equatorial ligand coordination and how this affects the basicity of the oxo ligands. Such an understanding will later apply to designing ligands incorporating functionalities that can bind uranyl both equatorially and axially for highly selective sequestration. Efficient and durable chromatography supports for lanthanide separation will be generated by (1) identifying robust peptoid-based ligands capable of binding different lanthanides with variable affinities, and (2) developing practical synthetic methods for the attachment of these ligands to Dowex ion exchange resins.

Tracers development for the PET study of nicotinic receptors: [{sup 11}C]-mecamylamine and [{sup 11}C]-SIB 1553A. Tritium and carbon-11 radiolabelling of a serine proteinase inhibitor: the t-PA{sub stop}; Developpement de traceurs pour l'etude des recepteurs nicotiniques par TEP: la [{sup 11}C]-mecamylamine et le [{sup 11}C]SIB 1553A. Radiomarquages par le tritium et le carbone-11 d'un inhibiteur d'une serine protease: le t-PA{sub stop}

Energy Technology Data Exchange (ETDEWEB)

Sobrio, F.

2002-12-15

In order to develop radiotracers for the Positron Emission Tomography (PET), we labelled both the mecamylamine and SIB-1553A with carbon-11 to study the nicotinic cholinergic receptors (nAChRs). The radiosynthesis of [{sup 11}C]-t-PA{sub stop} and the labelling with tritium of one analogue were realized for cerebral ischemia PET studies. The [{sup 11}C]-mecamylamine, a non-competitive and non-selective nAChRs antagonist was synthesized in 45 min via a N-[{sup 11}C]-methylation reaction. In the rat brain, the ex vivo studies showed no radio-metabolite 45 min after the injection of [{sup 11}C]-mecamylamine. The uptake kinetics in the rat brain or in vivo by PET in the anesthetized baboon or in the conscious monkey, reached a plateau around 45-50 min after injection. However, the saturation or displacement experiments did not permit to exhibit nor a significant difference of labelling between the different cerebral regions nor a specific uptake. In consequence, the [{sup 11}C]-mecamylamine was not an appropriate radioligand for nAChRs PET study. The labelling of [{sup 11}C]-SIB 1553A, a selective agonist for the nicotinic {beta}4 subunit, required the synthesis in 5 steps (56% overall yield) of precursor for the incorporation of carbon-11. The radiosynthesis was performed in 36 min by a N-[{sup 11}C]-methylation reaction (yield: 75%). The [{sup 11}C]-t-PA{sub stop} was obtained from [{sup 11}C]-KCN with yields from 80 to 90%. For the first time with carbon-11, the formation of an amidine group was realized from a nitrile group. The labelling by isotopic exchange of hydrogen by tritium of the t-PA{sub stop} did not permit to obtain the [{sup 3}H]-t-PA{sub stop} but a tritiated analogue. This compound will be used to study its vectorization by micro-encapsulation. (author)

Zolpidem, a clinical hypnotic that affects electronic transfer, alters synaptic activity through potential GABA receptors in the nervous system without significant free radical generation.

Science.gov (United States)

Kovacic, Peter; Somanathan, Ratnasamy

2009-01-01

Zolpidem (trade name Ambien) has attracted much interest as a sleep-inducing agent and also in research. Attention has been centered mainly on receptor binding and electrochemistry in the central nervous system which are briefly addressed herein. A novel integrated approach to mode of action is presented. The pathways to be discussed involve basicity, reduction potential, electrostatics, cell signaling, GABA receptor binding, electron transfer (ET), pharmacodynamics, structure activity relationships (SAR) and side effects. The highly conjugated pyridinium salt formed by protonation of the amidine moiety is proposed to be the active form acting as an ET agent. Extrapolation of reduction potentials for related compounds supports the premise that zolpidem may act as an ET species in vivo. From recent literature reports, electrostatics is believed to play a significant role in drug action. The pyridinium cation displays molecular electrostatic potential which may well play a role energetically or as a bridging mechanism. An SAR analysis points to analogy with other physiologically active xenobiotics, namely benzodiazepines and paraquat in the conjugated iminium category. Inactivity of metabolites indicates that the parent is the active form of zolpidem. Absence of reactive oxygen species and oxidative stress is in line with minor side effects. In contrast, generally, the prior literature contains essentially no discussion of these fundamental biochemical relationships. Pharmacodynamics may play an important role. Concerning behavior at the blood-brain barrier, useful insight can be gained from investigations of the related cationic anesthetics that are structurally related to acetyl choline. Evidently, the neutral form of the drug penetrates the neuronal membrane, with the salt form operating at the receptor. The pathways of zolpidem have several clinical implications since the agent affects sedation, electroencephalographic activity, oxidative metabolites and

Suscetibilidade de Rhipicephalus (Boophilus microplus a carrapaticidas em Mato Grosso do Sul, Brasil Susceptibility of Rhipicephalus (Boophilus microplus to acaricides in Mato Grosso do Sul, Brazil

Directory of Open Access Journals (Sweden)

Alberto Gomes

2011-08-01

demonstrada aos distintos produtos testados sugere que a resistência do carrapato a diferentes classes esteja amplamente disseminada no Estado, motivo pelo qual recomenda-se a realização rotineira de testes de suscetibilidade antes da seleção e aplicação de produtos acaricidas para controle do carrapato.The cattle tick, Rhipicephalus (Boophilus microplus, is one of the most important ectoparasites of bovines, requiring adoption of control measures mainly in Bos taurus herds and its crossbreeds. Its control has becoming increasingly difficult due to selection of resistant populations by commercial products. This study aimed to know the status of cattle tick resistance to acaricides in the state of Mato Grosso do Sul. From October 2003 to October 2006 acaricide bioassays were conducted on cattle ticks from eleven of the most important livestock regions of the state. Adult immersion tests using regular commercial products according to label recommendations were followed by the evaluation of biological parameters. Twelve acaricide products containing one or more of seven active ingredients, from three chemical classes: amidine (amitraz, synthetic pyrethroid (cypermethrin, and organophosphates (chlorfenvinphos, chlorpyriphos, diazinon, dichlorvos, and ethion were tested. Low tick susceptibility was observed in all ranches, with several populations showing virtually no susceptibility to one or more products. Despite the great variation of susceptibility shown by the populations to each acaricide, a gradient of efficacy of these products was observed. Regardless of the acaricide class, the average efficacy of products containing a single active ingredient (19.94%-64.27% was generally lower than that showed by the mixtures, pyrethroid-organophosphate (46.38%-82.68% and between organophosphates (85.28%-97.68%. The mixture containing pyrethroid + OF + synergist + repellent (cypermethrin + chlorpyrifos + citronellal + piperonyl butoxide showed 100% efficacy, although it was

Bulk gold catalyzed oxidation reactions of amines and isocyanides and iron porphyrin catalyzed N-H and O-H bond insertion/cyclization reactions of diamines and aminoalcohols

Energy Technology Data Exchange (ETDEWEB)

Klobukowski, Erik [Iowa State Univ., Ames, IA (United States)

2011-01-01

conditions, it was found that the oxidative dehydrogenation of dibenzylamine to Nbenzylidenebenzylamine, with N-methylmorpholine N-oxide (NMMO), was nearly quantitative (96%) within 24 h. However, the reaction with oxygen was much slower, with only a 52% yield of imine product over the same time period. Moreover, the rate of reaction was found to be influenced by the nature of the amine N-oxide. For example, the use of the weakly basic pyridine N-oxide (PyNO) led to an imine yield of only 6% after 24 h. A comparison of amine N-oxide and O2 was also examined in the oxidation of PhCH{sub 2}OH to PhCHO catalyzed by bulk gold. In this reaction, a 52% yield of the aldehyde was achieved when NMMO was used, while only a 7% product yield was afforded when O{sub 2} was the oxidant after 48 h. The bulk gold-catalyzed oxidative dehydrogenation of cyclic amines generates amidines, which upon treatment with Aerosil and water were found to undergo hydrolysis to produce lactams. Moreover, 5-, 6-, and 7-membered lactams could be prepared through a one-pot reaction of cyclic amines by treatment with oxygen, water, bulk gold, and Aerosil. This method is much more atom economical than industrial processes, does not require corrosive acids, and does not generate undesired byproducts. Additionally, the gold and Aerosil catalysts can be readily separated from the reaction mixture. The second project involved studying iron(III) tetraphenylporphyrin chloride, Fe(TPP)Cl, as a homogeneous catalyst for the generation of carbenes from diazo reagents and their reaction with heteroatom compounds. Fe(TPP)Cl, efficiently catalyzed the insertion of carbenes derived from methyl 2-phenyldiazoacetates into O-H bonds of aliphatic and aromatic alcohols. Fe(TPP)Cl was also found to be an effective catalyst for tandem N-H and O-H insertion/cyclization reactions when 1,2-diamines and 1,2-alcoholamines were treated with diazo reagents. This approach provides a one-pot process for synthesizing piperazinones and