40 CFR 721.1580 - Disubstituted benzene ether, polymer with substituted phenol (generic).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Disubstituted benzene ether, polymer... Significant New Uses for Specific Chemical Substances § 721.1580 Disubstituted benzene ether, polymer with... chemical substance generically identified as disubstituted benzene ether, polymer with substituted phenol...

40 CFR 721.1580 - Disubstituted benzene ether, polymer with substituted phenol (generic).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Disubstituted benzene ether, polymer... Significant New Uses for Specific Chemical Substances § 721.1580 Disubstituted benzene ether, polymer with... chemical substance generically identified as disubstituted benzene ether, polymer with substituted phenol...

40 CFR 721.1580 - Disubstituted benzene ether, polymer with substituted phenol (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Disubstituted benzene ether, polymer... Significant New Uses for Specific Chemical Substances § 721.1580 Disubstituted benzene ether, polymer with... chemical substance generically identified as disubstituted benzene ether, polymer with substituted phenol...

40 CFR 721.1580 - Disubstituted benzene ether, polymer with substituted phenol (generic).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Disubstituted benzene ether, polymer... Significant New Uses for Specific Chemical Substances § 721.1580 Disubstituted benzene ether, polymer with... chemical substance generically identified as disubstituted benzene ether, polymer with substituted phenol...

Simple two-step synthesis of 2,4-disubstituted pyrroles and 3,5-disubstituted pyrrole-2-carbonitriles from enones.

PubMed

Kucukdisli, Murat; Ferenc, Dorota; Heinz, Marcel; Wiebe, Christine; Opatz, Till

2014-01-01

The cyclocondensation of enones with aminoacetonitrile furnishes 3,4-dihydro-2H-pyrrole-2-carbonitriles which can be readily converted to 2,4-disubstituted pyrroles by microwave-induced dehydrocyanation. Alternatively, oxidation of the intermediates produces 3,5-disubstituted pyrrole-2-carbonitriles.

40 CFR 721.10028 - Disubstituted benzene metal salts (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Disubstituted benzene metal salts... Specific Chemical Substances § 721.10028 Disubstituted benzene metal salts (generic). (a) Chemical... as disubstituted benzene metal salts (PMNs P-01-901 and P-01-902) are subject to reporting under this...

40 CFR 721.10028 - Disubstituted benzene metal salts (generic).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Disubstituted benzene metal salts... Specific Chemical Substances § 721.10028 Disubstituted benzene metal salts (generic). (a) Chemical... as disubstituted benzene metal salts (PMNs P-01-901 and P-01-902) are subject to reporting under this...

40 CFR 721.10028 - Disubstituted benzene metal salts (generic).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Disubstituted benzene metal salts... Specific Chemical Substances § 721.10028 Disubstituted benzene metal salts (generic). (a) Chemical... as disubstituted benzene metal salts (PMNs P-01-901 and P-01-902) are subject to reporting under this...

40 CFR 721.10028 - Disubstituted benzene metal salts (generic).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Disubstituted benzene metal salts... Specific Chemical Substances § 721.10028 Disubstituted benzene metal salts (generic). (a) Chemical... as disubstituted benzene metal salts (PMNs P-01-901 and P-01-902) are subject to reporting under this...

40 CFR 721.10028 - Disubstituted benzene metal salts (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Disubstituted benzene metal salts... Specific Chemical Substances § 721.10028 Disubstituted benzene metal salts (generic). (a) Chemical... as disubstituted benzene metal salts (PMNs P-01-901 and P-01-902) are subject to reporting under this...

In situ tetrazole templated chair-like decanuclear azido-cobalt(II) SMM containing both tetra- and octa-hedral Co(II) ions.

PubMed

Zhang, Yuan-Zhu; Gao, Song; Sato, Osamu

2015-01-14

An azido-bridged chair-like decanuclear cluster: [Co(II)10(bzp)8(Metz)2(N3)18]·4MeOH·3H2O (1, bzp = 2-benzoylpyridine and HMetz = 5-methyl-1H-tetrazole) was prepared with in situ tetrazolate anions as templates in a sealed system. 1 containing both octahedral and tetrahedral Co(II) ions exhibited slow relaxation of magnetization with an effective barrier of 26 K under an applied dc field of 1 kOe.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yuan, Bing; Bernstein, Elliot R., E-mail: erb@lamar.colostate.edu

Unimolecular decomposition of nitrogen-rich energetic molecules 1,2-bis(1H-tetrazol-1-yl)ethane (1-DTE), 1,2-bis(1H-tetrazol-5-yl)ethane (5-DET), N,N-bis(1H-tetrazol-5-yl)amine (BTA), and 5,5’-bis(tetrazolyl)hydrazine (BTH) has been explored via 283 nm two photon laser excitation. The maximum absorption wavelength in the UV-vis spectra of all four materials is around 186–222 nm. The N{sub 2} molecule, with a cold rotational temperature (<30 K), is observed as an initial decomposition product from the four molecules, subsequent to UV excitation. Initial decomposition mechanisms for these four electronically excited isolated molecules are explored at the complete active space self-consistent field (CASSCF) level. Potential energy surface calculations at the CASSCF(12,8)/6-31G(d) level illustrate that conical intersectionsmore » play an essential role in the decomposition mechanism. The tetrazole ring opens on the S{sub 1} excited state and through conical intersections (S{sub 1}/S{sub 0}){sub CI}, N{sub 2} product is formed on the ground state potential energy surface without rotational excitation. The tetrazole rings of all four energetic molecules open at the N1—N2 ring bond with the lowest energy barrier: the C—N bond opening has higher energy barrier than that for any of the N—N ring bonds. Therefore, the tetrazole rings open at their N—N bonds to release N{sub 2}. The vibrational temperatures of N{sub 2} product from all four energetic materials are hot based on theoretical calculations. The different groups (CH{sub 2}—CH{sub 2}, NH—NH, and NH) joining the tetrazole rings can cause apparent differences in explosive behavior of 1-DTE, 5-DTE, BTA, and BTH. Conical intersections, non-Born-Oppenheimer interactions, and dynamics are the key features for excited electronic state chemistry of organic molecules, in general, and energetic molecules, in particular.« less

40 CFR 721.984 - Amino-hydroxy sulfonaphthylazo-disubstituted phenyl azo benzene carboxylate salt (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

...-disubstituted phenyl azo benzene carboxylate salt (generic). 721.984 Section 721.984 Protection of Environment...-disubstituted phenyl azo benzene carboxylate salt (generic). (a) Chemical substance and significant new uses...-disubstituted phenyl azo benzene carboxylate salt (PMN P-00-0351) is subject to reporting under this section for...

40 CFR 721.984 - Amino-hydroxy sulfonaphthylazo-disubstituted phenyl azo benzene carboxylate salt (generic).

Code of Federal Regulations, 2011 CFR

2011-07-01

...-disubstituted phenyl azo benzene carboxylate salt (generic). 721.984 Section 721.984 Protection of Environment...-disubstituted phenyl azo benzene carboxylate salt (generic). (a) Chemical substance and significant new uses...-disubstituted phenyl azo benzene carboxylate salt (PMN P-00-0351) is subject to reporting under this section for...

40 CFR 721.984 - Amino-hydroxy sulfonaphthylazo-disubstituted phenyl azo benzene carboxylate salt (generic).

Code of Federal Regulations, 2012 CFR

2012-07-01

...-disubstituted phenyl azo benzene carboxylate salt (generic). 721.984 Section 721.984 Protection of Environment...-disubstituted phenyl azo benzene carboxylate salt (generic). (a) Chemical substance and significant new uses...-disubstituted phenyl azo benzene carboxylate salt (PMN P-00-0351) is subject to reporting under this section for...

40 CFR 721.984 - Amino-hydroxy sulfonaphthylazo-disubstituted phenyl azo benzene carboxylate salt (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

...-disubstituted phenyl azo benzene carboxylate salt (generic). 721.984 Section 721.984 Protection of Environment...-disubstituted phenyl azo benzene carboxylate salt (generic). (a) Chemical substance and significant new uses...-disubstituted phenyl azo benzene carboxylate salt (PMN P-00-0351) is subject to reporting under this section for...

40 CFR 721.984 - Amino-hydroxy sulfonaphthylazo-disubstituted phenyl azo benzene carboxylate salt (generic).

Code of Federal Regulations, 2013 CFR

2013-07-01

...-disubstituted phenyl azo benzene carboxylate salt (generic). 721.984 Section 721.984 Protection of Environment...-disubstituted phenyl azo benzene carboxylate salt (generic). (a) Chemical substance and significant new uses...-disubstituted phenyl azo benzene carboxylate salt (PMN P-00-0351) is subject to reporting under this section for...

Homochiral zinc(II) coordination compounds based on in-situ-generated chiral amino acid-tetrazole ligands: circular dichroism, excitation light-induced tunable photoluminescence, and energetic performance.

PubMed

Wang, Shuai-Hua; Zheng, Fa-Kun; Zhang, Ming-Jian; Liu, Zhi-Fa; Chen, Jun; Xiao, Yu; Wu, A-Qing; Guo, Guo-Cong; Huang, Jin-Shun

2013-09-03

We employed two pairs of new in-situ-generated chiral amino acid-tetrazole ligands in constructing homochiral Zn(II) coordination compounds: [Zn(tzet)]n (1a for (S)-tzet and 1b for (R)-tzet, H2tzet = N-[2-(1H-tetrazol-5-yl)ethyl]tryptophan) and [Zn(tzep)(H2O)2]·H2O (2a for (S)-tzep and 2b for (R)-tzep, H2tzep = N-[2-(1H-tetrazol-5-yl)ethyl]proline), which were hydrothermally synthesized and structurally characterized by single-crystal X-ray diffraction. Structural analysis reveals that 1 features a 2D homochiral framework generated by both tetrazolate and carboxylate bridges in tzet(2-) ligands. The isolated structure of 2 is stabilized by extensive hydrogen bonds, which leads to formation of a supramolecular 2D architecture. The absolute configuration induced at the nitrogen atoms of 1 and 2 is strictly related to the neighboring chiral carbon atoms by hydrogen-bond interactions. To further investigate their chirality, the combined experimental and theoretical analyses of circular dichroism spectra reveal the absolute configurations and nature of the Cotton effects. Solid-state excitation and emission spectra for 1 and 2 at room temperature were investigated with relevant density of states calculation, and tunable photoluminescence emission of 1 under different excitation wavelengths was discussed. As nitrogen-rich tetrazolate compounds, 1 and 2 possess higher enthalpies of combustion and may serve as a new family of promising energetic materials.

Synthesis, Photophysical and Computational Study of Novel Coumarin-based Organic Dyes.

PubMed

Kumbar, Mahadev N; Sannaikar, Madivalagouda S; Shaikh, Saba Kauser J; Kamble, Atulkumar A; Wari, Manjunath N; Inamdar, Sanjeev R; Qiao, Qiquan; Revanna, Bhavya N; Madegowda, Mahendra; Dasappa, Jagadeesh P; Kamble, Ravindra R

2018-03-01

A series of novel coumarin pyrazoline moieties combined with tetrazoles, 3-(1-phenyl-4-(1H-tetrazol-5-yl)-1H-pyrazol-3-yl)-2H-chromen-2-one, 6-chloro-3-(1-phenyl-4-(1H-tetrazol-5-yl)-1H-pyrazol-3-yl)-2H-chromen-2-one, 6-bromo-3-(1-phenyl-4-(1H-tetrazol-5-yl)-1H-pyrazol-3-yl)-2H-chromen-2-one and 6-bromo-3-(1-(4-bromophenyl)-4-(1H-tetrazol-5-yl)-1H pyrazol-3-yl)-2H-chromen-2-one7(a-d), were designed and synthesized. Single crystal X-ray diffraction and their interactions were studied by Hirshfeld surface analysis. Thermal stabilities and electrochemical properties of these compounds were examined from differential scanning calorimetry (DSC), thermogravimetric (TGA) and cyclic voltammetric (CV) studies. Their spectroscopic properties were analyzed in various alcohols and general solvents by UV-Vis absorption, fluorescence and time-resolved spectroscopy. In addition, the ground and excited state electronic properties were investigated using density functional theory (DFT). The calculated highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) and energy band gap (E g ) values have revealed the effect of substitution of halogens. The substitution has equally affected the ground and excited states of 7(a-d) compounds. The solvatochromism on absorption, fluorescence spectra and fluorescence lifetimes of these compounds was investigated. All these results showed the chromen-2-one of pyrazoline tetrazole derivatives could play an important role in photonic and electronic devices. © 2017 The American Society of Photobiology.

Calcium oxalate crystal growth modification; investigations with confocal Raman microscopy

NASA Astrophysics Data System (ADS)

McMulkin, Calum J.; Massi, Massimiliano; Jones, Franca

2017-06-01

Confocal Raman Microscopy (CRM) in combination with a photophysical investigation has been employed to give insight into the interaction between calcium oxalate monohydrate (COM) and a series of tetrazole containing crystal growth modifier's (CGM's), in conjunction with characterisation of morphological changes using scanning electron and optical microscopy. The tetrazole CGM's were found to interact by surface adsorption with minimal morphological changes to the COM crystals however, significant interactions via chemisorption were observed; it was discovered that the chemisorption is sufficiently strong for aggregation of the tetrazole species to occur within the crystal during crystallisation.

Metal-organic coordination architectures of tetrazole heterocycle ligands bearing acetate groups: Synthesis, characterization and magnetic properties

NASA Astrophysics Data System (ADS)

Hu, Bo-Wen; Zheng, Xiang-Yu; Ding, Cheng

2015-12-01

Two new coordination complexes with tetrazole heterocycle ligands bearing acetate groups, [Co(L)2]n (1) and [Co3(L)4(N3)2·2MeOH]n (2) (L=tetrazole-1-acetate) have been synthesized and structurally characterized. Single crystal structure analysis shows that the cobalt-complex 1 has the 3D 3,6-connected (42.6)2(44.62.88.10)-ant topology. By introducing azide in this system, complex 2 forms the 2D network containing the [Co3] units. And the magnetic properties of 1 and 2 have been studied.

40 CFR 721.10050 - Disubstituted-N′- hydroxy-benzenecarboximidamide (generic).

Code of Federal Regulations, 2011 CFR

2011-07-01

... Specific Chemical Substances § 721.10050 Disubstituted-N′- hydroxy-benzenecarboximidamide (generic). (a... generically as disubstituted-N′- hydroxy-benzenecarboximidamide (PMN P-02-929) is subject to reporting under...

40 CFR 721.10050 - Disubstituted-N′- hydroxy-benzenecarboximidamide (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

... Specific Chemical Substances § 721.10050 Disubstituted-N′- hydroxy-benzenecarboximidamide (generic). (a... generically as disubstituted-N′- hydroxy-benzenecarboximidamide (PMN P-02-929) is subject to reporting under...

A new synthesis of carboxyterfenadine (fexofenadine) and its bioisosteric tetrazole analogs.

PubMed

Di Giacomo, B; Coletta, D; Natalini, B; Ni, M H; Pellicciari, R

1999-09-30

A new synthesis of carboxyterfenadine (4), based on the conversion of a alpha-halo-alkylarylketone into the corresponding substituted 2-arylalkanoic ester, is described. The enantioselective synthesis of its two bioisosteric tetrazole analogs together with preliminary biological results are reported.

Preparation of bis-(1(2)H-tetrazol-5-yl)-amine monohydrate

DOEpatents

Naud, Darren L [Los Alamos, NM; Hiskey, Michael A [Los Alamos, NM

2003-05-27

A process of preparing bis-(1(2)H-tetrazol-5-yl)-amine monohydrate is provided including combining a dicyanamide salt, an azide salt and water to form a first reaction mixture, adding a solution of a first strong acid characterized as having a pKa of less than about 1 to said first reaction mixture over a period of time characterized as providing a controlled reaction rate so as to gradually form hydrazoic acid without loss of significant quantities of hydrazoic acid from the solution while heating the first reaction mixture at temperatures greater than about 65.degree. C., heating the resultant reaction mixture at temperatures greater than about 65.degree. C. for a period of time sufficient to substantially completely form a reaction product, treating the reaction product with a solution of a second strong acid to form a product of bis-(1(2)H-tetrazol-5-yl)-amine monohydrate, and, recovering the bis-(1(2)H-tetrazol-5-yl)-amine monohydrate product.

Synthesis and antimicrobial activity of new 1-[(tetrazol-5-yl)methyl] indole derivatives, their 1,2,4-triazole thioglycosides and acyclic analogs.

PubMed

El-Sayed, Weal A; Abdel Megeid, Randa E; Abbas, Hebat-Allah S

2011-07-01

New 1-[(tetrazol-5-yl)methyl]indole derivatives, their acyclic nucleoside analogs and the corresponding glycoside derivatives were synthesized. Furthermore, the [)(1,2,4-triazol-3-yl)methyl])-2H-tetrazole derivative as well as the corresponding thioglucoside were prepared. The synthesized compounds were tested for their antimicrobial activity against Aspergillus Niger, Penicillium sp, Candida albican, Bacillus subtilis, Streptococcus lacti, Escherichia coli, Pseudomonas sp., and streptomyces sp. Compounds 3, 5 and 19b exhibited potent antibacterial activity and compounds 4, 5 and 10 exhibited high activities against the tested fungi compared with fusidic acid.

5-(Methylthio)tetrazoles as Versatile Synthons in the Stereoselective Synthesis of Polycyclic Pyrazolines via Photoinduced Intramolecular Nitrile Imine–Alkene 1,3-Dipolar Cycloaddition

PubMed Central

Pla, Daniel; Tan, Derek S.; Gin, David Y.

2014-01-01

A key thioether substituent in readily accessible 2-alkyl-5-(methylthio)tetrazoles enables facile photoinduced denitrogenation and intramolecular nitrile imine 1,3-dipolar cycloaddition to afford a wide range of polycyclic pyrazoline products with excellent diastereoselectivity. The methylthio group red-shifts the UV absorbance of the tetrazole, obviating the requirement in all previous substrate systems for at least one aryl substituent, and can subsequently be converted into a variety of other functionalities. This synthetic platform has been applied to the concise total syntheses of the alkaloid natural products (±)-newbouldine and withasomnine. PMID:25114776

Synthesis and biochemical evaluation of triazole/tetrazole-containing sulfonamides against thrombin and related serine proteases

PubMed Central

Siles, Rogelio; Kawasaki, Yuko; Ross, Patrick; Freire, Ernesto

2011-01-01

A small library of 25 triazole/tetrazole-based sulfonamides have been synthesized and further evaluated for their inhibitory activity against thrombin, trypsin, tryptase and chymase. In general, the triazole-based sulfonamides inhibited thrombin more efficiently than the tetrazole counterparts. Particularly, compound 26 showed strong thrombin inhibition (Ki =880 nM) and significant selectivity against other human related serine proteases like trypsin (Ki =729 µM). Thrombin binding affinity of the same compound was determined by ITC and demonstrated that the binding of this new triazole-based scaffold is enthalpically driven, making it a good candidate for further development. PMID:21807511

40 CFR 721.2060 - Disubstituted benzenedicarboxylic acid (generic).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Disubstituted benzenedicarboxylic acid (generic). 721.2060 Section 721.2060 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.2060 Disubstituted benzenedicarboxylic acid (generic). (a) Chemical...

40 CFR 721.2060 - Disubstituted benzenedicarboxylic acid (generic).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Disubstituted benzenedicarboxylic acid (generic). 721.2060 Section 721.2060 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.2060 Disubstituted benzenedicarboxylic acid (generic). (a) Chemical...

40 CFR 721.2060 - Disubstituted benzenedicarboxylic acid (generic).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Disubstituted benzenedicarboxylic acid (generic). 721.2060 Section 721.2060 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.2060 Disubstituted benzenedicarboxylic acid (generic). (a) Chemical...

40 CFR 721.2060 - Disubstituted benzenedicarboxylic acid (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Disubstituted benzenedicarboxylic acid (generic). 721.2060 Section 721.2060 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.2060 Disubstituted benzenedicarboxylic acid (generic). (a) Chemical...

40 CFR 721.2060 - Disubstituted benzenedicarboxylic acid (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Disubstituted benzenedicarboxylic acid (generic). 721.2060 Section 721.2060 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.2060 Disubstituted benzenedicarboxylic acid (generic). (a) Chemical...

40 CFR 721.10098 - Disubstituted benzoic acid, alkali metal salt (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

... metal salt (generic). 721.10098 Section 721.10098 Protection of Environment ENVIRONMENTAL PROTECTION... New Uses for Specific Chemical Substances § 721.10098 Disubstituted benzoic acid, alkali metal salt... identified generically as disubstituted benzoic acid, alkali metal salt (PMN P-03-643) is subject to...

40 CFR 721.10098 - Disubstituted benzoic acid, alkali metal salt (generic).

Code of Federal Regulations, 2011 CFR

2011-07-01

... metal salt (generic). 721.10098 Section 721.10098 Protection of Environment ENVIRONMENTAL PROTECTION... New Uses for Specific Chemical Substances § 721.10098 Disubstituted benzoic acid, alkali metal salt... identified generically as disubstituted benzoic acid, alkali metal salt (PMN P-03-643) is subject to...

Undergraduate Organic Experiment: Tetrazole Formation by Microwave Heated (3 + 2) Cycloaddition in Aqueous Solution

ERIC Educational Resources Information Center

DeFrancesco, Heather; Dudley, Joshua; Coca, Adiel

2018-01-01

An undergraduate experiment for the organic laboratory is described that utilizes microwave heating to prepare 5- substituted 1H-tetrazole derivatives through a (3 + 2) cycloaddition between aryl nitriles and sodium azide. The reaction mixture is analyzed by thin layer chromatography. The products are purified through an acid-base extraction and…

Quantum-Mechanical Studies on Chemical Reactivity and Ballistic Chemistry. VII. Semiempirical Molecular Orbital Calculations and Experimental Studies on Relative Chemical Reactivities of Isomeric Tetrazole Derivatives, and their Relationship to the Explosive Properties of some Tetrazole Derivatives

DTIC Science & Technology

1981-10-01

factor of about 20) than the methyl protons of the isomeric 2-phenyl compound-^6. Furthermore, when N-(4-dimethylaminophenyl) nitrones are reacted...34Tetrazoles from N-(4-Dimethylaminophenyl) nitrones and Hydrogen Azide", J. Heteroayol. Chem., 14, 757 (1977). 17 Further examples of...r—» , M < =< e 40 X rH u 03 ■l-J ■P u 0 6 H o u u 1— cd +J 1= c S B ■H u a> ft X U-l D W HJ -J H) o 0 Kl O < ■H a TS

Preparation of 3,5-disubstituted pyrazoles and isoxazoles from terminal alkynes, aldehydes, hydrazines, and hydroxylamine.

PubMed

Harigae, Ryo; Moriyama, Katsuhiko; Togo, Hideo

2014-03-07

The reaction of terminal alkynes with n-BuLi, and then with aldehydes, followed by the treatment with molecular iodine, and subsequently hydrazines or hydroxylamine provided the corresponding 3,5-disubstituted pyrazoles or isoxazoles in good yields with high regioselectivity, through the formations of propargyl secondary alkoxides and α-alkynyl ketones. The present reactions are one-pot preparation of 3,5-disubstituted pyrazoles from terminal alkynes, aldehydes, molecular iodine, and hydrazines, and 3,5-disubstituted isoxazoles from terminal alkynes, aldehydes, molecular iodine, and hydroxylamine.

A facile and regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles using click chemistry

EPA Science Inventory

The reaction of α-tosyloxy ketones, sodium azide and terminal alkynes in presence of copper(I) in aqueous polyethylene glycol afforded regioselectively 1,4-disubstituted 1,2,3-triazoles in good yield at ambient temperature. The one-pot exclusive formation of 1,4-disubstituted 1,2...

Conversion of Arylboronic Acids to Tetrazoles Catalyzed by ONO Pincer-Type Palladium Complex.

PubMed

Vignesh, Arumugam; Bhuvanesh, Nattamai S P; Dharmaraj, Nallasamy

2017-01-20

A convenient synthesis of a library of tetrazoles through a novel and operationally simple protocol effecting the direct conversion of arylboronic acids catalyzed by a new ONO pincer-type Pd(II) complex under mild reaction conditions using the readily available reagents is reported. The palladium complex was reused up to four cycles in an open-flask condition.

Palladium/IzQO-Catalyzed Coordination-Insertion Copolymerization of Ethylene and 1,1-Disubstituted Ethylenes Bearing a Polar Functional Group.

PubMed

Yasuda, Hina; Nakano, Ryo; Ito, Shingo; Nozaki, Kyoko

2018-02-07

Coordination-insertion copolymerization of ethylene with 1,1-disubstituted ethylenes bearing a polar functional group, such as methyl methacrylate (MMA), is a long-standing challenge in catalytic polymerization. The major obstacle for this process is the huge difference in reactivity of ethylene versus 1,1-disubstituted ethylenes toward both coordination and insertion. Herein we report the copolymerization of ethylene and 1,1-disubstituted ethylenes by using an imidazo[1,5-a]quinolin-9-olate-1-ylidene-supported palladium catalyst. Various types of 1,1-disubstituted ethylenes were successfully incorporated into the polyethylene chain. In-depth characterization of the obtained copolymers and mechanistic inferences drawn from stoichiometric reactions of alkylpalladium complexes with methyl methacrylate and ethylene indicate that the copolymerization proceeds by the same coordination-insertion mechanism that has been postulated for ethylene.

Mechanistic studies on the phosphoramidite coupling reaction in oligonucleotide synthesis. I. Evidence for nucleophilic catalysis by tetrazole and rate variations with the phosphorus substituents.

PubMed Central

Dahl, B H; Nielsen, J; Dahl, O

1987-01-01

Tetrazole catalyzed reactions of a series of phosphoramidites, 5'-O-DMTdT-3'-O-P(OR1)NR2(2) (1a-h), with 3'-O-SiButPh2-6-N-benzoyl-dA (2a) in acetonitrile solution have been studied. It is found that the coupling rate depends very much on whether tetrazole is added before or after 2a, and that dialkylammonium tetrazolide salts are inhibitors. These and other facts are evidence that the reactions are subjected to nucleophilic catalysis by tetrazole, in addition to acid catalysis. The rate variations with phosphorus substituents of 1a-h are NEt2 greater than NPri2 greater than N(CH2CH2)O greater than NMePh, and OMe greater than OCH2CH2CN greater than OCHMeCH2CN greater than OCMe2CH2CN much greater than OC6H4Cl. The inhibitor properties of dialkylammonium tetrazolides have practical consequences for the efficiency of DNA syntheses, when in situ prepared phosphoramidites are used; the same would apply for segmented, simultaneous syntheses or syntheses where recycling is performed. PMID:3822837

Polymer composites containing nanotubes

NASA Technical Reports Server (NTRS)

Bley, Richard A. (Inventor)

2008-01-01

The present invention relates to polymer composite materials containing carbon nanotubes, particularly to those containing singled-walled nanotubes. The invention provides a polymer composite comprising one or more base polymers, one or more functionalized m-phenylenevinylene-2,5-disubstituted-p-phenylenevinylene polymers and carbon nanotubes. The invention also relates to functionalized m-phenylenevinylene-2,5-disubstituted-p-phenylenevinylene polymers, particularly to m-phenylenevinylene-2,5-disubstituted-p-phenylenevinylene polymers having side chain functionalization, and more particularly to m-phenylenevinylene-2,5-disubstituted-p-phenylenevinylene polymers having olefin side chains and alkyl epoxy side chains. The invention further relates to methods of making polymer composites comprising carbon nanotubes.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yuan, Bing; Bernstein, Elliot R., E-mail: erb@Colostate.edu

Unimolecular decomposition of nitrogen-rich energetic salt molecules bis(ammonium)5,5′-bistetrazolate (NH{sub 4}){sub 2}BT and bis(triaminoguanidinium) 5,5′-azotetrazolate TAGzT, has been explored via 283 nm laser excitation. The N{sub 2} molecule, with a cold rotational temperature (<30 K), is observed as an initial decomposition product, subsequent to UV excitation. Initial decomposition mechanisms for the two electronically excited salt molecules are explored at the complete active space self-consistent field (CASSCF) level. Potential energy surface calculations at the CASSCF(12,8)/6-31G(d) ((NH{sub 4}){sub 2}BT) and ONIOM (CASSCF/6-31G(d):UFF) (TAGzT) levels illustrate that conical intersections play an essential role in the decomposition mechanism as they provide non-adiabatic, ultrafast radiationless internalmore » conversion between upper and lower electronic states. The tetrazole ring opens on the S{sub 1} excited state surface and, through conical intersections (S{sub 1}/S{sub 0}){sub CI}, N{sub 2} product is formed on the ground state potential energy surface without rotational excitation. The tetrazole rings open at the N2—N3 ring bond with the lowest energy barrier: the C—N ring bond opening has a higher energy barrier than that for any of the N—N ring bonds: this is consistent with findings for other nitrogen-rich neutral organic energetic materials. TAGzT can produce N{sub 2} either by the opening of tetrazole ring or from the N=N group linking its two tetrazole rings. Nonetheless, opening of a tetrazole ring has a much lower energy barrier. Vibrational temperatures of N{sub 2} products are hot based on theoretical predictions. Energy barriers for opening of the tetrazole ring for all the nitrogen-rich energetic materials studied thus far, including both neutral organic molecules and salts, are in the range from 0.31 to 2.71 eV. Energy of the final molecular structure of these systems with dissociated N{sub 2} product is in the range from −1.86 to 3.11 eV. The main difference between energetic salts and neutral nitrogen-rich energetic material is that energetic salts usually have lower excitation energy.« less

Effect of counter-ion on packing and crystal density of 5,5'-(3,3'-bi[1,2,4-oxadiazole]-5,5'-diyl)bis(1 H -tetrazol-1-olate) with five different cations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giles, Ian D.; DeHope, Alan J.; Zuckerman, Nathaniel B.

In energetic materials, the crystal density is an important parameter that affects the performance of the material. When making ionic energetic materials, the choice of counter-ion can have detrimental or beneficial effects on the packing, and therefore the density, of the resulting energetic crystal. Presented herein are a series of five ionic energetic crystals, all containing the dianion 5,5′-(3,3′-bi[1,2,4-oxadiazole]-5,5′-diyl)bis(1 H -tetrazol-1-olate), with the following cations: hydrazinium ( 1 ) (2N 2 H 5 + ·C 6 N 12 O 4 2− ), hydroxylammonium ( 2 ) 2NH 4 O + ·C 6 N 12 O 4 2− [Pagoria et al..more » (2017). Chem. Heterocycl. Compd , 53 , 760–778; included for comparison], dimethylammonium ( 3 ) (2C 2 H 8 N + ·C 6 N 12 O 4 2− ), 5-amino-1 H -tetrazol-4-ium ( 4 ) (2CH 4 N 5 + ·C 6 N 12 O 4 2− ·4H 2 O), and aminoguanidinium ( 5 ) (2CH 7 N 4 + ·C 6 N 12 O 4 2− ). Both the supramolecular interactions and the sterics of the cation play a role in the density of the resulting crystals, which range from 1.544 to 1.873 Mg m −1 . In 5 , the tetrazolate ring is disordered over two positions [occupancy ratio 0.907 (5):0.093 (5)] due to a 180° rotation in the terminal tetrazole rings.« less

Effect of counter-ion on packing and crystal density of 5,5'-(3,3'-bi[1,2,4-oxadiazole]-5,5'-diyl)bis(1 H -tetrazol-1-olate) with five different cations

DOE PAGES

Giles, Ian D.; DeHope, Alan J.; Zuckerman, Nathaniel B.; ...

2018-03-09

In energetic materials, the crystal density is an important parameter that affects the performance of the material. When making ionic energetic materials, the choice of counter-ion can have detrimental or beneficial effects on the packing, and therefore the density, of the resulting energetic crystal. Presented herein are a series of five ionic energetic crystals, all containing the dianion 5,5′-(3,3′-bi[1,2,4-oxadiazole]-5,5′-diyl)bis(1 H -tetrazol-1-olate), with the following cations: hydrazinium ( 1 ) (2N 2 H 5 + ·C 6 N 12 O 4 2− ), hydroxylammonium ( 2 ) 2NH 4 O + ·C 6 N 12 O 4 2− [Pagoria et al..more » (2017). Chem. Heterocycl. Compd , 53 , 760–778; included for comparison], dimethylammonium ( 3 ) (2C 2 H 8 N + ·C 6 N 12 O 4 2− ), 5-amino-1 H -tetrazol-4-ium ( 4 ) (2CH 4 N 5 + ·C 6 N 12 O 4 2− ·4H 2 O), and aminoguanidinium ( 5 ) (2CH 7 N 4 + ·C 6 N 12 O 4 2− ). Both the supramolecular interactions and the sterics of the cation play a role in the density of the resulting crystals, which range from 1.544 to 1.873 Mg m −1 . In 5 , the tetrazolate ring is disordered over two positions [occupancy ratio 0.907 (5):0.093 (5)] due to a 180° rotation in the terminal tetrazole rings.« less

Steering the azido-tetrazole equilibrium of 4-azidopyrimidines via substituent variation - implications for drug design and azide-alkyne cycloadditions.

PubMed

Thomann, A; Zapp, J; Hutter, M; Empting, M; Hartmann, R W

2015-11-21

This paper focuses on an interesting constitutional isomerism called azido-tetrazole equilibrium which is observed in azido-substituted N-heterocycles. We present a systematic investigation of substituent effects on the isomer ratio within a 2-substituted 4-azidopyrimidine model scaffold. NMR- and IR-spectroscopy as well as X-ray crystallography were employed for thorough analysis and characterization of synthesized derivatives. On the basis of this data, we demonstrate the possibility to steer this valence tautomerism towards the isomer of choice by means of substituent variation. We show that the tetrazole form can act as an efficient disguise for the corresponding azido group masking its well known reactivity in azide-alkyne cycloadditions (ACCs). In copper(I)-catalyzed AAC reactions, substituent-stabilized tetrazoles displayed a highly decreased or even abolished reactivity whereas azides and compounds in the equilibrium were directly converted. By use of an acid sensitive derivative, we provide, to our knowledge, the first experimental basis for a possible exploitation of this dynamic isomerism as a pH-dependent azide-protecting motif for selective SPAAC conjugations in aqueous media. Finally, we demonstrate the applicability and efficiency of stabilized tetrazolo[1,5-c]pyrimidines for Fragment-Based Drug Design (FBDD) in the field of quorum sensing inhibitors.

Analgesic Activity of Some 1,2,4-Triazole Heterocycles Clubbed with Pyrazole, Tetrazole, Isoxazole and Pyrimidine

PubMed Central

Gajanan Khanage, Shantaram; Raju, Appala; Baban Mohite, Popat; Bhanudas Pandhare, Ramdas

2013-01-01

Purpose: In the present study in vivo analgesic activity of some previously synthesized 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and pyrimidine ring have been evaluated. Methods: Acetic acid induced writhing method and Hot plate method has been described to study analgesic activity of some 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and pyrimidine as a pharmacological active lead. Results: Thirty six different derivatives containing 1,2,4-triazole ring were subjected to study their in vivo analgesic activity. Chloro, nitro and methoxy, hydroxy and bromo substituted derivatives showed excellent analgesic activity and dimethylamino, furan and phenyl substituted derivatives showed moderate analgesic activity in both of the methods. Compounds IIIa, IIId, IIIf, IIIi, IIIj, IVa, IVb, IVd, IVf, IVh, IVj IV3a and IIj were found to be superior analgesic agents after screening by Acetic acid induced writhing method. Compounds IIIb, IIId, IIIf, IIIh, IIIj, IVa, IVb, IVd, IVf, IVh, IVi, IV3c, IV3e and IIj were showed analgesic potential after screening of Hot plate method. Conclusion: All tested compounds containing 1,2,4-triazole were found to be promising analgesic agents, for this activity pyrazole, tetrazole, isoxazole and pyrimidine leads might be supported. PMID:24312806

Design and synthesis of carbazole carboxamides as promising inhibitors of Bruton’s tyrosine kinase (BTK) and Janus kinase 2 (JAK2)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Qingjie; Batt, Douglas G.; Lippy, Jonathan S.

Four series of disubstituted carbazole-1-carboxamides were designed and synthesised as inhibitors of Bruton’s tyrosine kinase (BTK). 4,7- and 4,6-disubstituted carbazole-1-carboxamides were potent and selective inhibitors of BTK, while 3,7- and 3,6-disubstituted carbazole-1-carboxamides were potent and selective inhibitors of Janus kinase 2 (JAK2).

Synthesis of 1,2,4-Triazoles via Oxidative Heterocyclization: Selective C-N Bond Over C-S Bond Formation.

PubMed

Gogoi, Anupal; Guin, Srimanta; Rajamanickam, Suresh; Rout, Saroj Kumar; Patel, Bhisma K

2015-09-18

The higher propensity of C-N over C-S bond forming ability was demonstrated, through formal C-H functionalization during the construction of 4,5-disubstituted 1,2,4-triazole-3-thiones from arylidenearylthiosemicarbazides catalyzed by Cu(II). However, steric factors imparted by the o-disubstituted substrates tend to change the reaction path giving thiodiazole as the major or an exclusive product. Upon prolonging the reaction time, the in situ generated thiones are transformed to 4,5-disubstituted 1,2,4-triazoles via a desulfurization process. Two classes of heterocycles viz. 4,5-disubstituted 1,2,4-triazole-3-thiones and 4,5-disubstituted 1,2,4-triazoles can be synthesized from arylidenearylthiosemicarbazides by simply adjusting the reaction time. Desulfurization of 1,2,4-triazole-3-thiones is assisted by thiophilic Cu to provide 1,2,4-triazoles with concomitant formation of CuS and polynuclear sulfur anions as confirmed from scanning electron microscope and energy dispersive X-ray spectroscopy measurements. A one-pot synthesis of an antimicrobial compound has been successfully achieved following this strategy.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Lei; Bai, Yu; Min, Yu-Ting

Three different tetrazole-carboxylate ligands, monotetrazole-carboxylate H{sub 2}tza (H{sub 2}tza=1,5-tetrazole-diacetic acid), Hpztza (Hpztza=5-(2-pyrazinyl)tetrazole-2(1-methyl)acetic acid), ditetrazole-carboxylate H{sub 2}tzpha (H{sub 2}tzpha=1,3-di(tetrazole-5-yl)benzene-N2,N2′-diacetic acid) have been chosen to react with CdCl{sub 2}·6H{sub 2}O, resulting in the formation of three new compounds [Cd{sub 2}(tza){sub 2}] (1), [Cd(pztza){sub 2}] (2) and [Cd(tzpha)(CH{sub 3}OH){sub 2}] (3). The coordinate sites of the three ligands are major influenced by the different substituted group of tetrazole ring. These compounds have been characterized by elemental analysis, IR and single crystal X-ray diffraction. Compound 1 displays a complex 3D structure; compound 2 shows a 3D network and compound 3 features a 2D layermore » network. Furthermore, the luminescence properties investigated at room temperature in the solid state showed excellent ligand-centered luminescence. The obvious enhancement in luminescence makes these compounds potential materials for optical use. The differential scanning calorimetry (DSC) and thermogravimetric-differential thermogravimetric (TG-DTG) analyses were applied to evaluate the thermal decomposition behavior of such compounds, showing that compounds 2 and 3 can be used as potential energetic materials. The relevant thermodynamic parameters ΔH, ΔS and ΔG were calculated as well. - Graphical abstract: H{sub 2}tza, Hpztza and H{sub 2}tzpha have been prepared. Three novel Cd (II)compounds were synthesized by reactions of CdCl{sub 2}·6H{sub 2}O, namely three dimensional [Cd{sub 2}(tza){sub 2}] (1), three dimensional [Cd(pztza){sub 2}] (2), and two dimensional [Cd(tzpha)(CH{sub 3}O){sub 2}] (3). The luminescences were investigated. Furthermore, the DSC show compounds 1 and 3 can be used as potential explosive materials.« less

Synthesis of enantiopure trans-2,5-disubstituted trifluoromethylpyrrolidines and (2S,5R)-5-trifluoromethylproline.

PubMed

Lubin, Hodney; Pytkowicz, Julien; Chaume, Grégory; Sizun-Thomé, Gwenaëlle; Brigaud, Thierry

2015-03-06

Enantiopure trans-2,5-disubstituted trifluoromethylpyrrolidines were prepared on a several gram scale starting from a readily available chiral fluorinated oxazolidine (Fox). A pure oxazolopyrrolidine intermediate could be obtained after an efficient separation by selective diastereomer destruction. The addition of various Grignard reagents on this oxazolopyrrolidine provided disubstituted pyrrolidines with moderate to complete trans diastereoselectivity. The highly valuable compound (2S,5R)-5-trifluoromethylproline could be synthesized from the same oxazolopyrrolidine intermediate via a Strecker-type reaction.

Novel quinazoline ring synthesis by cycloaddition of N-arylketenimines with N,N-disubstituted cyanamides.

PubMed

Shimizu, Masao; Oishi, Akihiro; Taguchi, Yoichi; Gama, Yasuo; Shibuya, Isao

2002-03-01

The reaction of N-aryl-substituted ketenimines with N,N-disubstituted cyanamides or (MeS)2C=N-CN under high pressure afforded 4-(N,N-disubstituted amino) or 4-(MeS)2C=N-substituted quinazoline derivatives, respectively. These products were formed by [4+2] cycloaddition between the aza-diene moieties of the N-arylsubstituted ketenimines and cyano groups. A 4-(unsubstituted amino)quinazoline derivative was synthesized by hydrolysis of the latter product.

5-(1-Aryl-3-(thiophen-2-yl)-1H-pyrazol-4-yl)-1H-tetrazoles: Synthesis, structural characterization, Hirshfeld analysis, anti-inflammatory and anti-bacterial studies

NASA Astrophysics Data System (ADS)

Kumbar, Mahadev N.; Kamble, Ravindra R.; Dasappa, Jagadeesh Prasad; Bayannavar, Praveen K.; Khamees, Hussien Ahmed; Mahendra, M.; Joshi, Shrinivas D.; Dodamani, Suneel; Rasal, V. P.; Jalalpure, Sunil

2018-05-01

A series of novel 5-(1-aryl-3-(thiophen-2-yl)-1H-pyrazol-4-yl)-1H-tetrazoles 7(h-s) were designed and synthesized. Structural characterization was done by spectral and single crystal X-ray studies. The intermolecular interactions of compound 7n were quantified and visualized using Hirshfeld surface analysis. Structures of newly synthesized compounds were docked into active site of COX-2 enzyme PDB:

Carboxylic acid isosteres improve the activity of ring-fused 2-pyridones that inhibit pilus biogenesis in E. coli

PubMed Central

Åberg, Veronica; Das, Pralay; Chorell, Erik; Hedenström, Mattias; Pinkner, Jerome S.; Hultgren, Scott J.; Almqvist, Fredrik

2009-01-01

Ring-fused 2-pyridones, termed pilicides, are small synthetic compounds that inhibit pilus assembly in uropathogenic E. coli. Their biological activity is clearly dependent upon a carboxylic acid functionality. Here we present the synthesis and biological evaluation of carboxylic acid isosteres, including e.g. tetrazoles, acyl sulfonamides and hydroxamic acids, of two lead 2-pyridones. Two independent biological evaluations show that acyl sulfonamides and tetrazoles significantly improve pilicide activity against uropathogenic E. coli. PMID:18499455

An x-ray diffraction study of some mesoionic 2,3-diphenyltetrazoles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luboradzki, R.; Kozminski, W.; Stefaniak, L.

1993-02-01

An X-my diffraction study is reported for four molecules of mesoionic 2,3-diphenyltetrazoles. The results confirm a dipolar [open quotes]mesoionic[close quotes] structure, aromatic character of the tetrazole ring and no conjugation between the phenyl and tetrazole rings. The geometry of the exocyclic group is discussed in detail. The molecular parameters of the compounds investigated are correlated with [sup 13]C and [sup 15]N nmr data. The results obtained are compared with similar structures which have already been studied.

Synthesis and biological evaluation of some N-(3-(1H-tetrazol-5-yl) phenyl)acetamide derivatives as novel non-carboxylic PTP1B inhibitors designed through bioisosteric modulation.

PubMed

Maheshwari, Neelesh; Karthikeyan, Chandrabose; Bhadada, Shraddha V; Sahi, Chandan; Verma, Amit K; Hari Narayana Moorthy, N S; Trivedi, Piyush

2018-06-08

Described herein is the synthesis and biological evaluation of a series of non-carboxylic inhibitors of Protein Tyrosine Phosphatase 1B designed using bioisosteric replacement strategy. Six N-(3-(1H-tetrazol-5-yl)phenyl)acetamide derivatives designed employing the aforementioned strategy were synthesized and screened for PTP1B inhibitory activity. Among the synthesized compounds, compound NM-03 exhibited the most potent inhibitory activity with IC 50 value of 4.48 µM. Docking studies with NM-03 revealed the key interactions with desired amino acids in the binding site of PTP1B. Furthermore, compound NM-03 also elicited good in vivo activity. Taken together, the results of this study establish N-(3-(1H-tetrazole-5-yl)phenyl)-2-(benzo[d]oxazol-2-ylthio)acetamide (NM-03) as a valuable lead molecule with great potential for PTP1B inhibitor development targeting diabetes. Copyright © 2018 Elsevier Inc. All rights reserved.

Conjugation in multi-tetrazole derivatives: a new design direction for energetic materials.

PubMed

Sun, Shuyang; Lu, Ming

2018-06-23

Multi-tetrazole derivatives with conjugated structures were designed and investigated in this study. Using quantum chemistry methods, the crystal structures, electrostatic potentials (ESPs), multicenter bond orders, HOMO-LUMO energy gaps, and detonation properties of the derivatives were calculated. As expected, these molecules with conjugated structures showed low energies of their crystal structures, molecular layering in their crystals, high average ESPs, high multicenter bond order values, and enhanced detonation properties. The derivative 1,2-di(1H-tetrazol-5-yl)diazene (N2) was predicted to have the best density (1.87 g/cm 3 ), detonation velocity (9006 m/s), and detonation pressure (36.8 GPa) of the designed molecules, while its total crystal energy was low, suggesting that it is relatively stable. Its sensitivity was also low, as the molecular stacking that occurs in its crystal allows external forces to be dissipated into movements of crystal layers. Finally, its multicenter bond order was high, indicating a highly conjugated structure.

Proline-catalysed asymmetric amination of alpha,alpha-disubstituted aldehydes: synthesis of configurationally stable enantioenriched alpha-aminoaldehydes.

PubMed

Vogt, Henning; Vanderheiden, Sylvia; Bräse, Stefan

2003-10-07

Proline-catalysed amination of alpha,alpha-disubstituted racemic aldehydes with azodicarboxylates proceeds smoothly to give configurationally stable scalemic aldehydes and oxazolidinones in up to 86% ee.

Pauson-Khand adducts of N-Boc-propargylamine: a new approach to 4,5-disubstituted cyclopentenones.

PubMed

Aiguabella, Nuria; Pesquer, Albert; Verdaguer, Xavier; Riera, Antoni

2013-06-07

A new approach to the synthesis of 4,5-disubstituted cyclopentenones is described. The strategy is based on the Pauson-Khand (PK) reaction of norbornadiene and N-Boc-propargylamine as an alkyne with a masked leaving group, which can be eliminated at will. This approach to the synthesis of 4,5-disubstituted cyclopentenones overcomes the problem of using the alkylation to introduce the α side chain. As an example, prostane 13-epi-12-oxo-phytodienoic acid (13-epi-12-oxo-PDA) methyl ester was synthesized.

Discovery of (pyridin-4-yl)-2H-tetrazole as a novel scaffold to identify highly selective matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis.

PubMed

Schnute, Mark E; O'Brien, Patrick M; Nahra, Joe; Morris, Mark; Howard Roark, W; Hanau, Cathleen E; Ruminski, Peter G; Scholten, Jeffrey A; Fletcher, Theresa R; Hamper, Bruce C; Carroll, Jeffery N; Patt, William C; Shieh, Huey S; Collins, Brandon; Pavlovsky, Alexander G; Palmquist, Katherine E; Aston, Karl W; Hitchcock, Jeffrey; Rogers, Michael D; McDonald, Joseph; Johnson, Adam R; Munie, Grace E; Wittwer, Arthur J; Man, Chiu-Fai; Settle, Steven L; Nemirovskiy, Olga; Vickery, Lillian E; Agawal, Arun; Dyer, Richard D; Sunyer, Teresa

2010-01-15

Potent, highly selective and orally-bioavailable MMP-13 inhibitors have been identified based upon a (pyridin-4-yl)-2H-tetrazole scaffold. Co-crystal structure analysis revealed that the inhibitors bind at the S(1)(') active site pocket and are not ligands for the catalytic zinc atom. Compound 29b demonstrated reduction of cartilage degradation biomarker (TIINE) levels associated with cartilage protection in a preclinical rat osteoarthritis model. Copyright 2009 Elsevier Ltd. All rights reserved.

Microwave-Assisted Piloty-Robinson Synthesis of 3,4-Disubstituted Pyrroles

PubMed Central

Milgram, Benjamin C.; Eskildsen, Katrine; Richter, Steven M.; Scheidt, W. Robert; Scheidt, Karl A.

2007-01-01

The synthesis of N-acyl 3,4-disubstituted pyrroles can be accomplished directly from hydrazine and an aldehyde via a Piloty-Robinson pyrrole synthesis. The use of microwave radiation for the cyclization and pyrrole formation greatly reduces the time necessary for this process and facilitates moderate to good yields from hydrazine for the corresponding 3,4-disubstituted products (5–12). By simple hydrolysis, the free N–H pyrroles can be accessed after the Piloty-Robinson reaction and then used directly in the synthesis of octaethylporphyrin (H2OEP, 14) and octaethyltetraphenylporphyrin (H2OETPP, 15). PMID:17432915

Enantio- and Diastereoselective Cyclopropanation of 1-Alkenylboronates: Synthesis of 1-Boryl-2,3-Disubstituted Cyclopropanes.

PubMed

Carreras, Javier; Caballero, Ana; Pérez, Pedro J

2018-02-23

A novel, highly enantio- and diastereoselective synthesis of 1-boryl-2,3-disubstituted cyclopropanes has been developed by means of the cyclopropanation of alkenylboronates with ethyl diazoacetate in the presence of catalytic amounts of a chiral copper(I) complex. The products can also be directly accessed from alkynes through an operationally simple, sequential hydroboration-cyclopropanation protocol. The resulting enantioenriched 1-boryl-2,3-disubstituted cyclopropanes are versatile synthetic intermediates that undergo further transformations at the carbon-boron bond. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Syntheses, crystal structures and characterization of nitrogen-rich salts based on bis (1H-tetrazol-5-yl) methanone oxime

NASA Astrophysics Data System (ADS)

Lin, Xinyu; Guo, Weiming; Zhang, Tianhe; Huang, Jingru; Tong, Yi; Zhang, Tonglai

2017-08-01

Two nitrogen-rich energetic salts (NH4)2(bto) (1) and (NH3OH)2(bto)·H2O (2) [H2bto = Bis (1H-tetrazol-5-yl) methanone oxime] were synthesized by an improved method in which water was used as solvent. These compounds were characterized by FT-IR spectroscopy, elemental analysis and single crystal X-ray diffraction. Their crystal structures were confirmed to belong to monoclinic system with space group P21 for 1 and Pc for 2, respectively. The detailed thermal behaviours were investigated by using differential scanning calorimetry (DSC) and thermogravimetric method (TG) (decomposition temperature >250 °C). The enthalpies of formation were calculated through the experimental values of combustion enthalpy. In addition, the sensitivities toward impact and friction were tested with standard methods, and those results indicated that two compounds are all insensitive (impact >40 J and friction >360 N). In short, both of the compounds show potential usages as energetic materials. The improved process opens a door for exploring nitrogen-rich salts based on Bis (1H-tetrazol-5-yl) methanone oxime.

Molecular Modelling of the H2 -Adsorptive Properties of Tetrazolate-Based Metal-Organic Frameworks: From the Cluster Approach to Periodic Simulations.

PubMed

Brea, Oriana; Luna, Alberto; Díaz, Cristina; Corral, Inés

2018-06-05

Hydrogen has been proposed as a long-term non-fossil fuel to be used in a future ideal carbon-neutral energetic economy. However, its low volumetric energy density hinders its storage and transportation. Metal-organic frameworks (MOFs) represent very promising materials for this purpose due to their very extended surface areas. Azolates, in particular tetrazolates, are - together with carboxylate functionalities - very common organic linkers connecting metallic secondary building units in MOFs. This study addresses, from a theoretical perspective, the H 2 adsorptive properties of tetrazolate linkers at the molecular level, following a size-progressive approach. Specifically, we have investigated how the physisorption energies and geometries are affected when changing the environment of the linker by considering the azolates in the gas phase, immersed in a finite cluster, or being part of an infinite extended crystal material. Furthermore, we also study the H 2 adsorptive capacity of these linkers within the cluster model. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

40 CFR 721.10097 - Disubstituted benzenesulfonic acid, alkali metal salt (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

..., alkali metal salt (generic). 721.10097 Section 721.10097 Protection of Environment ENVIRONMENTAL... metal salt (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as disubstituted benzenesulfonic acid, alkali metal salt (PMN P...

40 CFR 721.10097 - Disubstituted benzenesulfonic acid, alkali metal salt (generic).

Code of Federal Regulations, 2011 CFR

2011-07-01

..., alkali metal salt (generic). 721.10097 Section 721.10097 Protection of Environment ENVIRONMENTAL... metal salt (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as disubstituted benzenesulfonic acid, alkali metal salt (PMN P...

Mesoporous Fluorinated Metal-Organic Frameworks with Exceptional Adsorption of Fluorocarbons and CFCs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Teng-Hao; Popov, Ilya; Kaveevivitchai, Watchareeya

2016-02-08

Two mesoporous fluorinated metal–organic frameworks (MOFs) were synthesized from extensively fluorinated tritopic carboxylate- and tetrazolate-based ligands. The tetrazolate-based framework MOFF-5 has an accessible surface area of 2445 m 2g -1, the highest among fluorinated MOFs. Crystals of MOFF-5 adsorb hydrocarbons, fluorocarbons, and chlorofluorocarbons (CFCs)—the latter two being ozone-depleting substances and potent greenhouse species—with weight capacities of up to 225%. The material exhibits an apparent preference for the adsorption of non-spherical molecules, binding unusually low amounts of both tetrafluoromethane and sulfur hexafluoride.

Ferric Hydrogensulfate [Fe(HSO4)3] As a Reusable Heterogeneous Catalyst for the Synthesis of 5-Substituted-1H-Tetrazoles and Amides

PubMed Central

Eshghi, Hossein; Seyedi, Seyed Mohammad; Zarei, Elaheh Rahimi

2011-01-01

Ferric hydrogensulfate catalyzed the synthesis of 5-substituted 1H-tetrazoles via [2 + 3] cycloaddition of nitriles and sodium azide. This method has the advantages of high yields, simple methodology, and easy workup. The catalyst can be recovered by simple filtration and reused delivering good yields. Also, ferric hydrogensulfate catalyzed the hydrolysis of nitriles to primary amides under aqueous conditions. Various aliphatic and aromatic nitriles converted to the corresponding amides in good yields without any contamination with carboxylic acids. PMID:24052817

Asymmetric synthesis of all-carbon benzylic quaternary stereocenters via Cu-catalyzed conjugate addition of dialkylzinc reagents to 5-(1-arylalkylidene) Meldrum's acids.

PubMed

Fillion, Eric; Wilsily, Ashraf

2006-03-08

The asymmetric synthesis of all-carbon benzylic quaternary stereocenters has been successfully achieved through copper-catalyzed addition of dialkylzinc reagents to 5-(1-arylalkylidene) and 5-(dihydroindenylidene) Meldrum's acids in the presence of phosphoramidite ligand. The resulting benzyl-substituted Meldrum's acids and 1,1-disubstituted indanes were obtained in good yields and up to 99% ee. The significance of substituting the position para, meta, and ortho to the electrophilic benzylic center was highlighted. A benzyl Meldrum's acid product was further transformed to a 3,3-disubstituted 1-indanone and a beta,beta-disubstituted pentanoic acid.

40 CFR 721.8850 - Disubstituted halogenated pyridinol.

Code of Federal Regulations, 2011 CFR

2011-07-01

... SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.8850 Disubstituted halogenated pyridinol. (a) Chemical substances and significant new uses... pyridinol (PMN P-88-1274) is subject to reporting under this section for the significant new uses described...

40 CFR 721.8850 - Disubstituted halogenated pyridinol.

Code of Federal Regulations, 2012 CFR

2012-07-01

... SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.8850 Disubstituted halogenated pyridinol. (a) Chemical substances and significant new uses... pyridinol (PMN P-88-1274) is subject to reporting under this section for the significant new uses described...

40 CFR 721.8850 - Disubstituted halogenated pyridinol.

Code of Federal Regulations, 2013 CFR

2013-07-01

... SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.8850 Disubstituted halogenated pyridinol. (a) Chemical substances and significant new uses... pyridinol (PMN P-88-1274) is subject to reporting under this section for the significant new uses described...

40 CFR 721.8850 - Disubstituted halogenated pyridinol.

Code of Federal Regulations, 2014 CFR

2014-07-01

... SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.8850 Disubstituted halogenated pyridinol. (a) Chemical substances and significant new uses... pyridinol (PMN P-88-1274) is subject to reporting under this section for the significant new uses described...

40 CFR 721.8850 - Disubstituted halogenated pyridinol.

Code of Federal Regulations, 2010 CFR

2010-07-01

... SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.8850 Disubstituted halogenated pyridinol. (a) Chemical substances and significant new uses... pyridinol (PMN P-88-1274) is subject to reporting under this section for the significant new uses described...

1,2-Disubstituted Alkenes as Migratory Insertion Participants in Zn(II)-Promoted Metalloamination/Cyclization of N,N-Dimethylhydrazinoalkenes.

PubMed

Sunsdahl, Bryce; Mickelsen, Ky; Zabawa, Sean; Anderson, Bryon K; Livinghouse, Tom

2016-11-04

Diethylzinc-mediated metalloamination/cyclization of unsaturated N,N-dimethylhydrazines has been extended to the use of 1,2-disubstituted alkenes as N-Zn migratory insertion acceptors. Representative 2-arylethenes and vinylcyclopropanes readily serve as reaction participants in metalloamination/cyclization-allylation cascades.

40 CFR 721.4720 - Disubstituted phenoxazine, chlorometalate salt.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Disubstituted phenoxazine, chlorometalate salt. 721.4720 Section 721.4720 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.4720...

Synthesis of 6-amino-5-cyano-1,4-disubstituted-2(1H)-pyrimidinones via copper-(I)-catalyzed alkyne-azide 'click chemistry' and their reactivity.

PubMed

Najahi, Ennaji; Sudor, Jan; Chabchoub, Fakher; Nepveu, Françoise; Zribi, Fethi; Duval, Romain

2010-12-03

In this paper we present the room temperature synthesis of a novel serie of 1,4-disubstituted-1,2,3-triazoles 4a-l by employing the (3+2) cycloaddition reaction of pyrimidinones containing alkyne functions with different model azides in the presence of copper sulphate and sodium ascorbate. To obtain the final triazoles, we also synthesized the major precursors 6-amino-5-cyano-1,4-disubstituted-2(1H)-pyrimidinones 3a-r from ethyl 2,2-dicyanovinylcarbamate derivatives 2a-c and various primary aromatic amines containing an alkyne group. The triazoles were prepared in good to very good yields.

Replacement of the double bond of antitubulin chalcones with triazoles and tetrazoles: Synthesis and biological evaluation.

PubMed

Mesenzani, Ornella; Massarotti, Alberto; Giustiniano, Mariateresa; Pirali, Tracey; Bevilacqua, Valentina; Caldarelli, Antonio; Canonico, Pierluigi; Sorba, Giovanni; Novellino, Ettore; Genazzani, Armando A; Tron, Gian Cesare

2011-01-15

In the chalcone scaffold, it is thought that the double bond is an important structural linker but it is likely not essential for the interaction with tubulin. Yet, it may be a potential site of metabolic degradation and interaction with biological nucleophiles. In this letter, we have replaced this olefinic portion of chalcones with two metabolically stable and chemically inert heterocyclic rings, namely triazole or tetrazole. Yet, our biologic data suggest that, unlike in other antitubulinic structures, the olephinic ring might not be merely a structural linker. Copyright © 2010 Elsevier Ltd. All rights reserved.

Smart tetrazole-based antibacterial nanoparticles as multifunctional drug carriers for cancer combination therapy.

PubMed

Zakerzadeh, Elham; Salehi, Roya; Mahkam, Mehrdad

2017-12-01

Due to multidrug resistance of cancer tissues and immune-suppression of cancerous patients during chemotherapy in one hand and the use of tetrazole derivatives in medicine because of its anticancer, antifungal, and antiviral properties, on the other, we were encouraged to design novel smart antibacterial nanocomposites-based polymer of tetrazole as dual anticancer drug delivery systems. The structures of nanocomposites characterized by FTIR, 1 H NMR, FESEM-EDX, and TGA analyzes and antibacterial activity of smart carriers were evaluated by determination of minimum inhibitory concentration (MIC) values against some bacteria and fungi. Then, the pH-responsive manner of both nanocomposites was proved by checking their release profiles at pH of the physiological environment (pH 7.4) and pH of tumor tissues (mildly acidic). Finally, the potential antitumoral activity of these nanocomposite systems against MCF7 cell lines was evaluated by MTT assay and cell cycle studies. The results demonstrated that the novel developed nanocomposites not only meet our expectations about simultaneous release of two anticancer drugs according to the predicted profile but also showed antibacterial and anticancer properties in vitro experimental. Moreover, it was proved that these carriers have tremendous potential in multifunctional drug delivery in cancer therapy.

Synthesis of 3,3-disubstituted oxindoles by visible-light-mediated radical reactions of aryl diazonium salts with N-arylacrylamides.

PubMed

Fu, Weijun; Xu, Fengjuan; Fu, Yuqin; Zhu, Mei; Yu, Jiaqi; Xu, Chen; Zou, Dapeng

2013-12-06

A mild and efficient visible-light-mediated diarylation of N-arylacrylamides with aryl diazonium salts under mild conditions has been developed. This method provides convenient access to a variety of useful 3,3-disubstituted oxindoles by constructing two C-C bonds in one step.

Complexation and Structure Elucidation of the Axial Conformers of Mono- and (±)-trans-1,2-Disubstituted Cyclohexanes by Enantiopure Alleno-Acetylenic Cage Receptors.

PubMed

Gropp, Cornelius; Trapp, Nils

2018-04-25

Single crystal X-ray diffraction is a powerful method to unambiguously characterize the structure of molecules with atomic resolution. Herein, we review the molecular recognition of the (di)axial conformers of Mono- and (±)-trans-1,2-disubstituted cyclohexanes by enantiopure alleno-acetylenic cage receptors in solution and in the solid state. Single crystals of the host-guest complexes suitable for X-ray diffraction allow for the first time to study the dihedral angles of a series of Mono- and (±)-trans-1,2-disubstituted cyclohexanes in their (di)axial chair conformation. Theoretical studies indicate negligible influence of the host structure on the guest conformation, suggesting that the structural information obtained from the host-guest complexes give insight into the innate structures of Mono- and (±)-trans-1,2-disubstituted cyclohexanes. Strong deviation of the dihedral angles a,a(X-C(1)-C(2)-X) from the idealized 180° are observed, accompanied by substantial flattening of the ring dihedral angles ρ(X-C(1)-C(2)-C(3)).

Hydrogen-bond-driven electrophilic activation for selectivity control: scope and limitations of fluorous alcohol-promoted selective formation of 1,2-disubstituted benzimidazoles and mechanistic insight for rationale of selectivity.

PubMed

Chebolu, Rajesh; Kommi, Damodara N; Kumar, Dinesh; Bollineni, Narendra; Chakraborti, Asit K

2012-11-16

Hydrogen-bond-driven electrophilic activation for selectivity control during competitive formation of 1,2-disubstituted and 2-substituted benzimidazoles from o-phenylenediamine and aldehydes is reported. The fluorous alcohols trifluoroethanol and hexafluoro-2-propanol efficiently promote the cyclocondensation of o-phenylenediamine with aldehydes to afford selectively the 1,2-disubstituted benzimidazoles at rt in short times. A mechanistic insight is invoked by NMR, mass spectrometry, and chemical studies to rationalize the selectivity. The ability of the fluorous alcohols in promoting the reaction and controlling the selectivity can be envisaged from their better hydrogen bond donor (HBD) abilities compared to that of the other organic solvents as well as of water. Due to the better HBD values, the fluorous alcohols efficiently promote the initial bisimine formation by electrophilic activation of the aldehyde carbonyl. Subsequently the hydrogen-bond-mediated activation of the in situ-formed bisimine triggers the rearrangement via 1,3-hydride shift to form the 1,2-disubstituted benzimidazoles.

Novel axially disubstituted non-aggregated silicon phthalocyanines.

PubMed

Bıyıklıoğlu, Zekeriya; Cakır, Dilek

2012-12-01

This paper describes the synthesis, spectroscopic characterization of a range of new axially-disubstituted silicon phthalocyanines with 2-[2-(dimethylamino)ethoxy] or 2-[2-(1,4,7,10,13-pentaoxa-16-azacyclooctadecan-16-yl)ethoxy] groups as axial ligands. 2-[2-(Dimethylamino)ethoxy]ethanol 2, 2-[2-(1,4,7,10,13-pentaoxa-16-azacyclooctadecan-16-yl)ethoxy]ethanol 4 are reacted with silicon phthalocyanine 1, to give an axially-disubstituted silicon phthalocyanines 3 and 5. Axially-disubstituted silicon phthalocyanine complexes were synthesized at the first time. Newly synthesized silicon phthalocyanines were characterized by UV-Vis, IR, (1)H NMR, (13)C NMR spectroscopy, ESI mass spectrometry. These new silicon(IV) phthalocyanines 3 and 5 showed excellent solubility in organic solvents such as CHCl(3), CH(2)Cl(2), acetone, DMF, DMSO, THF, EtOAc. The aggregation behavior of these compounds were investigated in different concentrations of DMSO. The effect of solvents on absorption spectra were studied in various organic solvents. The thermal stabilities of the silicon(IV) phthalocyanines 3 and 5 were determined by thermogravimetric analysis. Copyright © 2012 Elsevier B.V. All rights reserved.

Unexpected formation of 1-[4-chloromethylphenyl]-5-[4-(methylsulfonyl)benzyl]-1H-tetrazole and 1-[4-chloromethylphenyl]-5-[4-(aminosulfonyl)phenyl]-1H-tetrazole: Crystal structure, bioassay screening and molecular docking studies

NASA Astrophysics Data System (ADS)

Jawabrah Al-Hourani, Baker; Ali, Basem F.; Judeh, Zaher; El-Barghouthi, Musa I.; Al-Awaida, Wajdy; Snobar, Yasmin; El Soubani, Fatima; Matalka, Khalid; Wuest, Frank

2018-07-01

During the cyclization reaction of benzyl alcohol containing amides, using NaN3 and SiCl4, additional unique chlorination development was observed to yield the novel azoles 1-[4-chloromethylphenyl]-5-[4-(methylsulfonyl)benzyl]-1H-tetrazole (3a) and 1-[4-chloromethylphenyl]-5-[4-(aminosulfonyl)phenyl]-1H-tetrazole (3b). Control experiments showed that the SiCl4 or SiCl3N3 has the major role for such functional group transformation in such a clean reaction and quantitative yield. Their molecular structures have been ascertained using the X-ray crystallography technique in addition to the spectroscopic analyses. Both compounds 3a and 3b crystallize in the monoclinic space group P21/c. The cell parameters of azole 3a are a = 22.3827 (8), Å, b = 5.1602 (2) Å, c = 13.4994 (5) Å3, β = 95.2352 (14)°, V = 1552.67 (10) Å3, and Z = 4. While the cell parameters of azole 3b are a = 20.582 (2), Å, b = 5.8947 (7) Å, c = 13.0796 (16) Å3, β = 104.376 (4)°, V = 1537.2 (3) Å3, and Z = 4. The central tetrazole ring of both compounds is planar and bears (4-chloromethylphenyl) at position one (N-1) of the central moiety. However, the substituents 4-(methylsulfonyl)phenyl and 4-(aminosulfonyl)phenyl of azoles 3a and 3b, respectively, are attached to the C-5 of the same central unit. The phenyl rings at N-1, (C2sbnd C7) and C9sbnd C14 in (3a); (C2sbnd C7) and (C8sbnd C14) in (3b) are inclined compared to the tetrazole ring with dihedral angles of 21.74° and 83.94° in 3a and 25.85° and 65.13° in 3b. The two phenyl rings, at N-1 and C-5, are rotated against each other by 87.73° (in 3a) and 72.21° (in 3b). In the crystal, intermolecular interactions between molecules of 3a,b are dominated by Csbnd H⋯O and Csbnd H⋯N hydrogen bonds. Additional Cl…π interactions add extra supramolecularity. All intermolecular interaction motifs consolidate a three dimensional network lattice. The molecular docking studies were carried out to understand the interaction of compounds 3a and 3b within the active site of the cyclooxygenase-2 enzyme, followed by a comparison study with the celecoxib drug as a reference compound. The in vitro bioassay screenings of azoles 3a and 3b showed that both compounds have poor selectivity and weak inhibition potency toward cyclooxygenase-2 enzyme.

Fusion of disubstituted benzenes.

PubMed

Martin, E; Yalkowsky, S H; Wells, J E

1979-05-01

The entropy of fusion of 84 disubstituted benzenes was essentially constant and independent of the participation of the compounds in intramolecular or intermolecular hydrogen bonding. It was also independent of the shapes, sizes, and dipole moments of the rigid molecules studied. While the entropy of fusion was independent of these parameters, the melting point and the heat of fusion showed a direct dependence on molecular properties.

ZINClick: a database of 16 million novel, patentable, and readily synthesizable 1,4-disubstituted triazoles.

PubMed

Massarotti, Alberto; Brunco, Angelo; Sorba, Giovanni; Tron, Gian Cesare

2014-02-24

Since Professors Sharpless, Finn, and Kolb first introduced the concept of "click reactions" in 2001 as powerful tools in drug discovery, 1,4-disubstituted-1,2,3-triazoles have become important in medicinal chemistry due to the simultaneous discovery by Sharpless, Fokin, and Meldal of a perfect click 1,3-dipolar cycloaddition reaction between azides and alkynes catalyzed by copper salts. Because of their chemical features, these triazoles are proposed to be aggressive pharmacophores that participate in drug-receptor interactions while maintaining an excellent chemical and metabolic profile. Surprisingly, no virtual libraries of 1,4-disubstituted-1,2,3-triazoles have been generated for the systematic investigation of the click-chemical space. In this manuscript, a database of triazoles called ZINClick is generated from literature-reported alkynes and azides that can be synthesized within three steps from commercially available products. This combinatorial database contains over 16 million 1,4-disubstituted-1,2,3-triazoles that are easily synthesizable, new, and patentable! The structural diversity of ZINClick ( http://www.symech.it/ZINClick ) will be explored. ZINClick will also be compared to other available databases, and its application during the design of novel bioactive molecules containing triazole nuclei will be discussed.

Two new Cu{sup I} compounds with zwitterionic tetrazolate ligand: In situ synthesis, crystal structures, luminescence and photocatalytic properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Jian-Yong; Xing, Yuan-Yuan; Wang, Qing-Wei

2015-12-15

Two 2D new Cu(I) coordination polymers, namely [Cu{sub 2}(mpTZ){sub 2}Br{sub 2}]·H{sub 2}O (1), and [Cu{sub 2}(mpTZ){sub 2}N{sub 3}]ClO{sub 4} (2) (mpTZ=N-methyl-4-pyridinium tetrazolate) have been synthesized under solvothermal conditions, in which the mpTZ ligands and Cu{sup I} ions were obtained through in situ [2+3] cycloaddition reaction and reduction reaction of Cu{sup II} salts, respectively. Both compounds have been structural characterized by single crystal X-ray diffraction, FT-IR, PXRD and EA. Compound 1 exhibits a 2D neutral coordination network, in which the Cu{sup I} ions are bridged by η{sub 3}−1, 2, 4-tetrazolate into 2D sheet. In compound 2, the Cu{sup I} ions aremore » linked by azide (in µ{sub 3}−1, 1, 3 bridging mode) and tetrazolate (in η{sub 3}−1, 2, 3 bridging mode) anions into 2D positively charged sheet, extended along the bc plane. Both compounds 1 and 2 exhibit intense bluish green luminescence in the solid state. Photocatalytic performances of the two compounds for the degradation of methylene blue (MB) under visible light were also investigated and the MB degradation in the presence of 1 was nearly complete (99%) after 150 min. - Graphical abstract: Two Cu{sup I}CPs have been solvothermally synthesized through the in situ [2+3] cycloaddition and metal reduction reaction. Both compounds exhibit intense luminescence and high photocatalytic degradation under visible light. - Highlights: • Two new Cu{sup I}-based CPs are solvothermally synthesized through in situ [2+3] cycloaddition reaction and metal reduction reaction. • Both compounds exhibit strong luminescence and photocatalytic degradation of methylene blue (MB) under visible light. • The MB degradation in the presence of 1 is nearly complete (99%) after 150 min.« less

New metal-organic complexes based on bis(tetrazole) ligands: Synthesis, structures and properties

NASA Astrophysics Data System (ADS)

Du, Ceng-Ceng; Fan, Jian-Zhong; Wang, Xin-Fang; Zhou, Sheng-Bin; Wang, Duo-Zhi

2017-04-01

In this paper, a series of new complexes, [Zn2(HL1)2(H2O)4]·H2O (1), [Co2(HL1)2]·TEA (2), [Co3(HL1)2(H2L1)2(H2O)4]n (3), [Cu(HL1)(H2O)2]n (4), {[Cu5(HL2)2(OH)4(ClO4)2]·4H2O}n (5) and [Cu2(L3)]n (6) were successfully prepared by utilizing three bis(tetrazole) ligands [bis-(1H-tetrazol-5-ylmethyl)-amine (H3L1), bis-(1H-tetrazol-5-ylethyl)-amine (H3L2) and 1,5-bis(5-tetrazolo)-3-thiapentane (H2L3)], all of which have been characterized by elemental analyses, FT-IR spectroscopy, powder X-ray diffraction (PXRD), thermogravimetric analyses as well as single-crystal X-ray diffraction analyses showing different dimensionalities (0D, 1D and 3D). Complexes 1 and 2 are 0D structures, 1 shows a dinuclear structure, 2 displays two crystallographically different mononuclear structures, 1 and 2 are further assembled to form 3D supramolecular framework and 2D supramolecular network by hydrogen-bonding interactions, respectively. Complexes 3, 4 and 5 are 1D structures, 3 features a mononuclear unit and a 1D chain, which are arranged into 3D supramolecular architecture by hydrogen-bonding interactions, 4 presents a zigzag chain, 5 shows an infinite chain structure constructed from pentanuclear Cu(II) subunits and ClO4- anions. Complex 6 exhibits a 3D coordination framework based on cyclic [Cu4(L3)2] dimmer subunits as nodes possessing an 8-connected network topology with the point symbol {424·64}. Further, semiconductor behaviors, the solid-state luminescent properties of the complexes 1-3 and 6 were measured and studied seriously at room temperature.

A set of new transition metal-based coordination complexes dependent upon Hpztza ligand (Hpztza=2-(5-(pyrazin-2-yl)-2H-tetrazol-2-yl) acetic acid)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang Jie; Shen Lei; Yang Gaowen, E-mail: ygwsx@126.com

2012-02-15

Reaction of MCl{sub 2}{center_dot}4H{sub 2}O (M=Zn, Cd, Mn, Co, Ni) with 2-(5-(pyrazin-2-yl)-2H-tetrazol-2-yl) acetic acid (Hpztza) yielded a set of new M(II)/pztza complexes, [Cd(pztza){sub 2}(H{sub 2}O){sub 6}]{center_dot}3H{sub 2}O{center_dot}(Hpztza) (1), [M(pztza){sub 2}(H{sub 2}O){sub 2}; M=Cd(2), Zn(7), Mn(9)], [Cd(pztza){sub 2}]{center_dot}2(CH{sub 3}OH) (3), [Co(pztza){sub 2}(H{sub 2}O){sub 2}]{center_dot}6H{sub 2}O (4), [Co(pztza)(H{sub 2}O)Cl] (6) and [M(pztza){sub 2}(H{sub 2}O){sub 2}]{center_dot}2H{sub 2}O [M=Co(5), Zn(8), Ni(10)]. These compounds were structurally characterized by elemental analysis, IR spectroscopy and X-ray single-crystal diffraction. Complex 1 featured a mononuclear structure, complexes 4, 5, 7, 8, 10 showed 1D chains and complexes 2, 3, 6, 9 displayed 2D layer structures. Furthermore, the luminescence propertiesmore » of 1-10 were investigated at room temperature in the solid state. - Graphical abstract: Ten new coordination polymers with 2-(5-(pyrazin-2-yl)-2H-tetrazol-2-yl) acetic acid (Hpztza) ligand have been synthesized and their structures have been characterized. All of the complexes show photoluminescence at room temperature. Highlights: Black-Right-Pointing-Pointer Ten novel transition metal-based coordination complexes with 2-(5-(pyrazin-2-yl)-2H-tetrazol-2-yl) acetic acid (Hpztza) are reported. Black-Right-Pointing-Pointer Complexes 1-10 are described as mononuclear structure, 1D and 2D frameworks with diverse architecture. Black-Right-Pointing-Pointer Six coordination complexes show emission at room temperature in the solid state.« less

Discovery of 3,5-disubstituted-1H-pyrrolo[2,3-b]pyridines as potent inhibitors of the insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patnaik, Samarjit; Stevens, Kirk L.; Gerding, Roseanne

2009-07-23

Exploration of the SAR around a series of 3,5-disubstituted-1H-pyrrolo[2,3-b]pyridines led to the discovery of novel pyrrolopyridine inhibitors of the IGF-1R tyrosine kinase. Several compounds demonstrated nanomolar potency in enzyme and cellular mechanistic assays.

Biting deterrence and insecticidal activity of hydrazide–hydrazones and their corresponding 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazoles against Aedes aegypti

USDA-ARS?s Scientific Manuscript database

BACKGROUND: Hydrazones are important compounds for drug design and they have also good insecticidal activity. In this study, A series of hydrazide–hydrazones (1-10) and 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazoles (11-20) were investigated for their biting deterrent and insecticidal act...

Revisiting the Nucleotide and Aminoglycoside Substrate Specificity of the Bifunctional Aminoglycoside Acetyltransferase(6′)-Ie/Aminoglycoside Phosphotransferase(2″)-Ia Enzyme*

PubMed Central

Frase, Hilary; Toth, Marta; Vakulenko, Sergei B.

2012-01-01

The bifunctional aminoglycoside-modifying enzyme aminoglycoside acetyltransferase(6′)-Ie/aminoglycoside phosphotransferase(2″)-Ia, or AAC(6′)-Ie/APH(2″)-Ia, is the major source of aminoglycoside resistance in Gram-positive bacterial pathogens. In previous studies, using ATP as the cosubstrate, it was reported that the APH(2″)-Ia domain of this enzyme is unique among aminoglycoside phosphotransferases, having the ability to inactivate an unusually broad spectrum of aminoglycosides, including 4,6- and 4,5-disubstituted and atypical. We recently demonstrated that GTP, and not ATP, is the preferred cosubstrate of this enzyme. We now show, using competition assays between ATP and GTP, that GTP is the exclusive phosphate donor at intracellular nucleotide levels. In light of these findings, we reevaluated the substrate profile of the phosphotransferase domain of this clinically important enzyme. Steady-state kinetic characterization using the phosphate donor GTP demonstrates that AAC(6′)-Ie/APH(2″)-Ia phosphorylates 4,6-disubstituted aminoglycosides with high efficiency (kcat/Km = 105-107 m−1 s−1). Despite this proficiency, no resistance is conferred to some of these antibiotics by the enzyme in vivo. We now show that phosphorylation of 4,5-disubstituted and atypical aminoglycosides are negligible and thus these antibiotics are not substrates. Instead, these aminoglycosides tend to stimulate an intrinsic GTPase activity of the enzyme. Taken together, our data show that the bifunctional enzyme efficiently phosphorylates only 4,6-disubstituted antibiotics; however, phosphorylation does not necessarily result in bacterial resistance. Hence, the APH(2″)-Ia domain of the bifunctional AAC(6′)-Ie/APH(2″)-Ia enzyme is a bona fide GTP-dependent kinase with a narrow substrate profile, including only 4,6-disubstituted aminoglycosides. PMID:23115238

One step N-glycosylation by filamentous fungi biofilm in bioreactor of a new phosphodiesterase-3 inhibitor tetrazole.

PubMed

de Melo Souza, Paula L; Arruda, Evilanna L; Pazini, Francine; Menegatti, Ricardo; Vaz, Boniek G; Lião, Luciano M; de Oliveira, Valéria

2016-07-01

An efficient and rapid process for N-glycosylation of 5-(1-(3-fluorophenyl)-1H-pyrazol-4-yl)-2H-tetrazole-LQFM 021 (1), a new synthetic derivative of pyrazole with phosphodiesterase-3 (PDE-3) inhibitory action, vasorelaxant activity and low toxicity catalyzed by filamentous fungi biofilm in bioreactor was successfully developed. A maximum N-glycosyl yield of 68% was obtained with Cunninghamella echinulata ATCC 9244 biofilm in bioreactor with conditions of 25mgml(-1) of 1 in PDSM medium at 28°C for 96h. After extraction with ethyl acetate, the derivative was identified by Ultrahigh Resolution Mass Spectrometry and (1)H-(13)C HSQC/HMBC. Copyright © 2016 Elsevier Ltd. All rights reserved.

One-pot synthesis of novel 1-(1H-tetrazol-5-yl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine derivatives via an Ugi-azide 4CR process.

PubMed

Ghandi, Mehdi; Salahi, Saleh; Taheri, Abuzar; Abbasi, Alireza

2018-05-01

A facile one-pot method has been developed for the synthesis of novel pyrrolo[2,1-a]pyrazine scaffolds. A variety of 1-(1H-tetrazol-5-yl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine derivatives were obtained in moderate to high yields in methanol using a one-pot four-component condensation of 1-(2-bromoethyl)-1H-pyrrole-2-carbaldehyde, amine, isocyanide and sodium azide at room temperature. These reactions presumably proceed via a domino imine formation, intramolecular annulation and Ugi-azide reaction. Unambiguous assignment of the molecular structures was carried out by single-crystal X-ray diffraction.

Non-aggregated axially disubstituted silicon phthalocyanines bearing electropolymerizable ligands and their aggregation, electropolymerizaton and thermal properties.

PubMed

Biyiklioglu, Zekeriya; Bas, Huseyin; Alp, Hakan

2015-08-21

A novel series of axially disubstituted silicon(iv) phthalocyanines bearing electropolymerizable ligands were designed and synthesized for the first time. The silicon(iv) phthalocyanines were characterized by various spectroscopic techniques as well as elemental analysis. The aggregation behavior of the SiPcs were examined in different solvents and at different concentrations in chloroform. In all the studied solvents and concentrations, the SiPcs were non-aggregated. The thermal behavior of the silicon(iv) phthalocyanines was also studied. The electropolymerization properties of the silicon(iv) phthalocyanines were investigated by cyclic and square wave voltammetry. This study is the first example of the electropolymerization of axially disubstituted silicon phthalocyanines. The type of axial ligand on the phthalocyanine ring did not show any effect on the absorption and thermal properties but influenced the electropolymerization of the phthalocyanines.

Synthesis and biological activity of hydrazide hydrazones and their corresponding 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazoles

USDA-ARS?s Scientific Manuscript database

Various new 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazoles (11-20) were prepared by the reaction of aryl substituted hydrazones of 4-fluorobenzoic acid hydrazide (1-10) with acetic anhydride. The structures of the newly synthesized compounds 11-20, were confirmed by UV, IR and 1H NMR spec...

Electropolymerizable peripherally tetra-{2-[3-(diethylamino)phenoxy]ethoxy} substituted as well as axially (4-phenylpiperazin-1-yl)propanoxy-disubstituted silicon phthalocyanines and their electrochemistry.

PubMed

Biyiklioglu, Zekeriya; Alp, Hakan

2015-11-21

A novel type of peripherally tetra-substituted as well as axially disubstituted silicon(iv) phthalocyanine containing electropolymerizable ligands was designed and synthesized for the first time. Axial bis-hydroxy silicon phthalocyanine 2 was prepared from 2(3),9(10),16(17),23(24)-tetrakis-{2-[3-(diethylamino)phenoxy]ethoxy}phthalocyanine 1 in dichloromethane by using 1.8-diazabicyclo[5.4.0]undec-7-ene (DBU) and trichlorosilane. Peripherally tetra and axially di-substituted silicon phthalocyanine 4 was synthesized from 2(3),9(10),16(17),23(24)-tetrakis-{2-[3-(diethylamino)phenoxy]ethoxy}silicon(iv)phthalocyanine dihydroxide 2 with 1-(3-chloropropyl)-4-phenylpiperazine 3 in toluene in the presence of NaH at 120 °C. These complexes were fully characterized by various spectroscopy techniques such as (1)H-NMR, (13)C-NMR, IR, UV-Vis, and MALDI-TOF spectroscopy and elemental analysis as well. Electropolymerization properties of silicon(IV) phthalocyanine complexes were investigated by cyclic and square wave voltammetry. Electrochemical studies reveal that silicon(IV) phthalocyanine complexes were electropolymerized on the working electrode during the anodic potential scan. This study is the first example of electropolymerization of both peripherally tetra and axially di-substituted silicon phthalocyanines on the same molecule.

Stereocontrolled Alkylative Construction of Quaternary Carbon Centers

PubMed Central

Kummer, David A.; Chain, William J.; Morales, Marvin R.; Quiroga, Olga; Myers, Andrew G.

2009-01-01

Protocols for the stereodefined formation of α,α-disubstituted enolates of pseudoephedrine amides are presented followed by the implementation of these in diastereoselective alkylation reactions. Direct alkylation of α,α-disubstituted pseudoephedrine amide substrates is demonstrated to be both efficient and diastereoselective across a range of substrates, as exemplified by alkylation of the diastereomeric pseudoephedrine α-methylbutyramides, where both substrates are found to undergo stereospecific replacement of the α-C-H bond with α-C-alkyl, with retention of stereochemistry. This is shown to arise by sequential stereospecific enolization and alkylation reactions, with the alkyl halide attacking a common π-face of the E- and Z-enolates, proposed to be that opposite the pseudoephedrine alkoxide side-chain. Pseudoephedrine α-phenylbutyramides are found to undergo highly stereoselective but not stereospecific α-alkylation reactions, which evidence suggests is due to facile enolate isomerization. Also, we show that α, α-disubstituted pseudoephedrine amide enolates can be generated in a highly stereocontrolled fashion by conjugate addition of an alkyllithium reagent to the s-cis-conformer of an α-alkyl-α,β-unsaturated pseudoephedrine amide, providing α,α-disubstituted enolate substrates that undergo alkylation in the same sense as those formed by direct deprotonation. Methods are presented to transform the α-quaternary pseudoephedrine amide products into optically active carboxylic acids, ketones, primary alcohols, and aldehydes. PMID:18788739

Synthesis of Novel 1,4- Dihydropyridine Derivatives Bearing Biphenyl-2'-Tetrazole Substitution as Potential Dual Angiotensin II Receptors and Calcium Channel Blockers

PubMed Central

Shahbazi Mojarrad, Javid; Zamani, Zahra; Nazemiyeh, Hossein; Ghasemi, Saeed; Asgari, Davoud

2011-01-01

Introduction: We report the synthesis of novel 1,4-dihydropyridine derivatives containing biphenyl-2'-tetrazole moieties. We hypothesized that merging the key structural elements present in an AT1 receptor antagonist with key structural elements in 1,4-dihydropyridine calcium channel blockers would yield novel analogs with potential dual activity for both receptors. This strategy led to the design and synthesis of dialkyl 1,4-dihydro-2,6-dimethyl-4-[2-n-alkyl-1-[2΄-(1H-tetrazole-5-yl) biphenyl -4-yl] methyl] imidazole-4(or 5)-yl]- 3, 5-pyridinedicarboxylate analogs. Methods: These compounds were obtained by two methods starting from biphenyltetrazolyl-4-(or 5)-imidazolecarboxaldehyde intermediates employing in classical Hantzsch condensation reaction. In the first method, triphenylmethyl protecting group of 4- or 5-carboxaldehyde intermediate was first removed in acidic media and then classical Hantzsch reaction was employed in order to obtain the final products. In the second method, without further deprotection process, protected 4- or 5-carboxaldehyde intermediate directly was used in Hantzsch reaction. Results: The second method was more efficient than the first method since the deprotection and ring closure reaction occurs simultaneously in one pot. Conclusion: Eight novel dihydropridines analogs were synthesized using classic Hantzsch condensation reaction. Chemical structures of the compounds were characterized by 1H NMR, infrared and mass spectroscopy. PMID:24312750

α-Carbamoylsulfides as N-Carbamoylimine Precursors in the Visible Light Photoredox-Catalyzed Synthesis of α,α-Disubstituted Amines.

PubMed

Lebée, Clément; Languet, Morgan; Allain, Clémence; Masson, Géraldine

2016-03-18

A general and practical photoredox-promoted addition of nucleophiles to N-acylimines generated in situ from α-amidosulfides using Ru(bpy)3(PF6)2 as the photocatalyst is reported. The broad scope of the reaction toward various nucleophiles and amidosulfide derivatives was explored. This novel protocol provides a rapid, mild, and efficient access to valuable α,α-disubstituted amines in respectable yields.

Planar conjugated polymers containing 9,10-disubstituted phenanthrene units for efficient polymer solar cells.

PubMed

Li, Guangwu; Kang, Chong; Li, Cuihong; Lu, Zhen; Zhang, Jicheng; Gong, Xue; Zhao, Guangyao; Dong, Huanli; Hu, Wenping; Bo, Zhishan

2014-06-01

Four novel conjugated polymers (P1-4) with 9,10-disubstituted phenanthrene (PhA) as the donor unit and 5,6-bis(octyloxy)benzothiadiazole as the acceptor unit are synthesized and characterized. These polymers are of medium bandgaps (2.0 eV), low-lying HOMO energy levels (below -5.3 eV), and high hole mobilities (in the range of 3.6 × 10(-3) to 0.02 cm(2) V(-1) s(-1) ). Bulk heterojunction (BHJ) polymer solar cells (PSCs) with P1-4:PC71 BM blends as the active layer and an alcohol-soluble fullerene derivative (FN-C60) as the interfacial layer between the active layer and cathode give the best power conversion efficiency (PCE) of 4.24%, indicating that 9,10-disubstituted PhA are potential donor materials for high-efficiency BHJ PSCs. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chirality and numbering of substituted tropane alkaloids.

PubMed

Humam, Munir; Shoul, Tarik; Jeannerat, Damien; Muñoz, Orlando; Christen, Philippe

2011-08-25

The strict application of IUPAC rules for the numbering of tropane alkaloids is not always applied by authors and there is hence a lot of confusion in the literature. In most cases, the notation of 3, 6/7-disubstituted derivatives has been chosen arbitrarily, based on NMR and MS data, without taking into account the absolute configuration of these two carbons. This paper discusses the problem and the relevance of CD and NMR to determine molecular configurations. We report on the use of (1)H-NMR anisochrony (Δδ) induced by the Mosher's chiral auxiliary reagents (R)-(-)- and (S)-(+)-α-methoxy-α-trifluoromethyl-phenylacetyl chlorides (MTPA-Cl), to determine the absolute configuration of (3R,6R)-3α-hydroxy-6β-senecioyloxytropane, a disubstituted tropane alkaloid isolated from the aerial parts of Schizanthus grahamii (Solanaceae). These analytical tools should help future works in correctly assigning the configuration of additional 3, 6/7 disubstituted tropane derivatives.

Halogenated Alkyltetrazoles for the Rational Design of FeII Spin-Crossover Materials: Fine-Tuning of the Ligand Size.

PubMed

Müller, Danny; Knoll, Christian; Seifried, Marco; Welch, Jan M; Giester, Gerald; Reissner, Michael; Weinberger, Peter

2018-04-06

1-(3-Halopropyl)-1H-tetrazoles and their corresponding Fe II spin-crossover complexes have been investigated in a combined experimental and theoretical study. Halogen substitution was found to positively influence the spin transition, shifting the transition temperature about 70 K towards room temperature. Halogens located at the ω position were found to be too far away from the coordinating tetrazole moiety to have an electronic impact on the spin transition. The subtle variation of the steric demand of the ligand in a highly comparable series was found to have a comparatively large impact on the spin-transition behavior, which highlights the sensitivity of the effect to subtle structural changes. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Discovery of 1,5-Disubstituted Pyridones: A New Class of Positive Allosteric Modulators of the Metabotropic Glutamate 2 Receptor

PubMed Central

2010-01-01

A series of 1,5-disubstituted pyridones was identified as positive allosteric modulators (PAMs) of the metabotropic glutamate receptor 2 (mGluR2) via high throughput screening (HTS). Subsequent SAR exploration led to the identification of several compounds with improved in vitro activity. Lead compound 8 was further profiled and found to attenuate the increase in PCP induced locomotor activity in mice. PMID:22778815

Excited-State Conformational/Electronic Responses of Saddle-Shaped N,N'-Disubstituted-Dihydrodibenzo[a,c]phenazines: Wide-Tuning Emission from Red to Deep Blue and White Light Combination.

PubMed

Zhang, Zhiyun; Wu, Yu-Sin; Tang, Kuo-Chun; Chen, Chi-Lin; Ho, Jr-Wei; Su, Jianhua; Tian, He; Chou, Pi-Tai

2015-07-08

A tailored strategy is utilized to modify 5,10-dimethylphenazine (DMP) to donor-acceptor type N,N'-disubstituted-dihydrodibenzo[a,c]phenazines. The representative compounds DMAC (N,N'-dimethyl), DPAC (N,N'-diphenyl), and FlPAC (N-phenyl-N'-fluorenyl) reveal significant nonplanar distortions (i.e., a saddle shape) and remarkably large Stokes-shifted emission independent of the solvent polarity. For DPAC and FlPAC with higher steric hindrance on the N,N'-substituents, normal Stokes-shifted emission also appears, for which the peak wavelength reveals solvent-polarity dependence. These unique photophysical behaviors are rationalized by electronic configuration coupled conformation changes en route to the geometry planarization in the excited state. This proposed mechanism is different from the symmetry rule imposed to explain the anomalously long-wavelength emission for DMP and is firmly supported by polarity-, viscosity-, and temperature-dependent steady-state and nanosecond time-resolved spectroscopy. Together with femtosecond early dynamics and computational simulation of the reaction energy surfaces, the results lead us to establish a sequential, three-step kinetics. Upon electronic excitation of N,N'-disubstituted-dihydrodibenzo[a,c]phenazines, intramolecular charge-transfer takes place, followed by the combination of polarization stabilization and skeletal motion toward the planarization, i.e., elongation of the π-delocalization over the benzo[a,c]phenazines moiety. Along the planarization, DPAC and FlPAC encounter steric hindrance raised by the N,N'-disubstitutes, resulting in a local minimum state, i.e., the intermediate. The combination of initial charge-transfer state, intermediate, and the final planarization state renders the full spectrum of interest and significance in their anomalous photophysics. Depending on rigidity, the N,N'-disubstituted-dihydrodibenzo[a,c]phenazines exhibit multiple emissions, which can be widely tuned from red to deep blue and even to white light generation upon optimization of the surrounding media.

Poly(ethylene glycol)s as grinding additives in the mechanochemical preparation of highly functionalized 3,5-disubstituted hydantoins.

PubMed

Mascitti, Andrea; Lupacchini, Massimiliano; Guerra, Ruben; Taydakov, Ilya; Tonucci, Lucia; d'Alessandro, Nicola; Lamaty, Frederic; Martinez, Jean; Colacino, Evelina

2017-01-01

The mechanochemical preparation of highly functionalized 3,5-disubstituted hydantoins was investigated in the presence of various poly(ethylene) glycols (PEGs), as safe grinding assisting agents (liquid-assisted grinding, LAG). A comparative study under dry-grinding conditions was also performed. The results showed that the cyclization reaction was influenced by the amount of the PEG grinding agents. In general, cleaner reaction profiles were observed in the presence of PEGs, compared to dry-grinding procedures.

Poly(ethylene glycol)s as grinding additives in the mechanochemical preparation of highly functionalized 3,5-disubstituted hydantoins

PubMed Central

Guerra, Ruben; Taydakov, Ilya; Tonucci, Lucia; d’Alessandro, Nicola; Lamaty, Frederic; Martinez, Jean

2017-01-01

The mechanochemical preparation of highly functionalized 3,5-disubstituted hydantoins was investigated in the presence of various poly(ethylene) glycols (PEGs), as safe grinding assisting agents (liquid-assisted grinding, LAG). A comparative study under dry-grinding conditions was also performed. The results showed that the cyclization reaction was influenced by the amount of the PEG grinding agents. In general, cleaner reaction profiles were observed in the presence of PEGs, compared to dry-grinding procedures. PMID:28179944

Scaffold hopping identifies 6,8-disubstituted purines as novel anaplastic lymphoma kinase inhibitors.

PubMed

Schlütke, Laura; Immer, Markus; Preu, Lutz; Totzke, Frank; Schächtele, Christoph; Kubbutat, Michael H G; Kunick, Conrad

2018-05-01

Rearrangements of anaplastic lymphoma kinase (ALK) are associated with several cancer diseases. Due to resistance development against existing ALK-inhibitors, new, structurally unrelated inhibitors are required. By a scaffold hopping strategy, 6,8-disubstituted purines were designed as analogues of similar ALK-inhibiting thieno[3,2-d]pyrimidines. While the new title compounds indeed inhibited ALK and several ALK mutants in submicromolar concentrations, they retained poor water solubility. Copyright © 2017 Elsevier B.V. All rights reserved.

Formation of Cyclopenta[c]pyridine Derivatives from 2,5-Disubstituted Pyrroles and 1,4-Dibromo-1,3-butadienes via Pyrrole-Ring One-Carbon Expansion.

PubMed

Yin, Jianhao; Ye, Qingyu; Hao, Wei; Du, Shuaijing; Gu, Yucheng; Zhang, Wen-Xiong; Xi, Zhenfeng

2017-01-06

Reactions between 1,4-dibromo-1,3-butadienes and 2,5-disubstituted pyrroles afforded cyclopenta[c]pyridine derivatives in high yield, catalyzed by palladium and a cyclopentadiene-phosphine ligand (L1). Insertion of one terminal carbon of the butadienyl skeleton into one C═C double bond in the pyrrole ring resulted in ring expansion, along with a 1,2-shift of an alkyl or an aryl substituent on the butadienes.

Assembly of N,N-disubstituted hydrazines and 1-aryl-1H-indazoles via copper-catalyzed coupling reactions.

PubMed

Xiong, Xiaodong; Jiang, Yongwen; Ma, Dawei

2012-05-18

CuI-catalyzed coupling of N-acyl-N'-substituted hydrazines with aryl iodides takes place at 60-90 °C to afford N-acyl-N',N'-disubstituted hydrazines regioselectively and thereby gives a facile method for assembling N,N-diaryl hydrazines. N-Acyl-N'-substituted hydrazines can also react with 2-bromoarylcarbonylic compounds at 60-125 °C under the catalysis of CuI/4-hydroxy-l-proline to provide 1-aryl-1H-indazoles.

Synthesis of Triazole Derivatives of Levoglucosenone As Promising Anticancer Agents: Effective Exploration of the Chemical Space through retro-aza-Michael//aza-Michael Isomerizations.

PubMed

Tsai, Yi-Hsuan; Borini Etichetti, Carla M; Di Benedetto, Carolina; Girardini, Javier E; Martins, Felipe Terra; Spanevello, Rolando A; Suárez, Alejandra G; Sarotti, Ariel M

2018-04-06

The design and synthesis of biomass-derived triazoles and the in vitro evaluation as potential anticancer agents are described. The discovery of base-catalyzed retro-aza-Michael//aza-Michael isomerizations allowed the exploration of the chemical space by affording novel types of triazoles, difficult to obtain otherwise. Following this strategy, 2,4-disubstituted 1,2,3-triazoles could be efficiently obtained from the corresponding 1,4-disubstituted analogues.

Bifunctional 3D porous Cu(I) metal-organic framework with gas sorption and luminescent properties

NASA Astrophysics Data System (ADS)

Xing, Guang'en; Zhang, Yan; Cao, Xiulian

2017-10-01

A new Cu(I) metal-organic framework, namely [Cu(L)]2n·n(H2O) (1 HL = 5-(4-Pyridyl)-1H-tetrazole), has been successfully synthesized via the solvothermal reactions of CuI and 5-(4-Pyridyl)-1H-tetrazole ligand, and further characterized by elemental analysis, powder X-ray diffraction analysis, thermal analysis and single crystal X-ray structural analysis. The L- ligand displays a μ4-N2, N3, N4, N5 coordination mode bridging Cu(I) ions into a 3D porous framework with the opened 1D channels filled by the lattice water molecules. Gas sorption investigations indicated that compound 1 can selectively adsorb CO2 over N2 at 298 K, and luminescent properties investigations revealed that compound 1 features luminescent sensing function for nitrobenzene.

Liquid chromatographic determination of 9-methyl-3-(1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-one in human plasma with fluorescence detection.

PubMed

Cheng, H; Pittman, K A; Dandekar, K A

1987-12-01

A simple and sensitive assay for quantitating 9-methyl-3-(1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-one (1; BMY 26517) in human plasma was developed using high-performance liquid chromatography with fluorescence detection. The method involves precipitation of protein and reversed-phase chromatography. The method is linear in the range of 4.3-429 ng/mL of 1, and the limit of detection is 0.4 ng/mL. The day-to-day precision values of this method at 25.7 and 386 ng/mL are 2.1 and 2.6%, respectively. The day-to-day accuracy values at these concentrations are 99.7 and 99.8%, respectively. The recovery of 1 is 98.3%.

Regioselective and stereoselective route to N2-β-tetrazolyl unnatural nucleosides via SN2 reaction at the anomeric center of Hoffer's chlorosugar.

PubMed

Bag, Subhendu Sekhar; Talukdar, Sangita; Anjali, S J

2016-04-15

We are reporting a regioselective and stereoselective route to N2-β-tetrazolyl aromatic donor/acceptor unnatural nucleosides as new class of possible DNA base analogs. The SN2 substitution reaction at the anomeric center of Hoffer's chlorosugar with various 5-substituted aromatic tetrazoles in THF in presence of K2CO3 proceeds with regioselectivity at N2-tetrazoles and stereoselectivity at α-chlorosugar with very good yield. The stereoelectronic and steric effects play a crucial role for the observed outcome which is also supported from a theoretical (DFT) study. The methodology is simple, eco-compatible and the tetrazolyl unnatural nucleosides might find applications in decorating DNA for various biotechnological and DNA based material science applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tetrazole amphiphile inducing growth of conducting polymers hierarchical nanostructures and their electromagnetic absorption properties

NASA Astrophysics Data System (ADS)

Xie, Aming; Sun, Mengxiao; Zhang, Kun; Xia, Yilu; Wu, Fan

2018-05-01

Conducting polymers (CPs) at nano scales endow materials with special optical, electrical, and magnetic properties. The crucial factor to construct and regulate the micro-structures of CPs is the inducing reagent, particular in its chemical structure, such active sites, self-assembling properties. In this paper, we design and synthesize an amphiphile bearing tetrazole moiety on its skeleton, and use this amphiphile as an inducing reagent to prepare and regulate the micro-structures of a series of CPs including polypyrrole, polyaniline, poly(3,4-ethylenedioxythiophene) and poly(p-phenylenediamine). Because of the unique electric properties of CPs and size effect, we next explored the electromagnetic absorption performances of these CPs nanostructures. A synergetic combination of electric loss and magnetic loss is used to explain the absorption mechanism of these CPs nano-structures.

Immobilization of 5-aminopyridine-2-tetrazole on cross-linked polystyrene for the preparation of a new adsorbent to remove heavy metal ions from aqueous solution.

PubMed

Zhang, Yu; Chen, Youning; Wang, Chaozhan; Wei, Yinmao

2014-07-15

Novel 5-aminopyridine-2-tetrazole-functionalized polystyrene resin (APTZ-PS) was prepared by anchoring 5-aminopyridine-2-carbonitrile onto chloromethylated polystyrene beads (CMPS) and subsequently using the cyano-tetrazole conversion reaction. The APTZ-PS resin was characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and specific surface area and pore size analyses. The adsorption experiments of the prepared resin for heavy metal ions were conducted by batch methods. The effects of the experimental conditions, such as pH, contact time and initial metal ion concentration on the adsorption properties of Cu(II), Pb(II) and Hg(II) were investigated. The results showed that the resin possessed perfect adsorption capacities for Cu(II), Pb(II) and Hg(II), and the selectivity was different from the commonly used iminodiacetic acid-chelating resin. The sorption kinetics of the three metal ions followed the pseudo-second-order equation. The adsorption isotherms for Cu(II) and Pb(II) could be better fitted by the Langmuir model than the Freundlich model, whereas the Freundlich model was the best for the Hg(II) ion. Even after five consecutive adsorption-desorption cycles, no obvious change in the adsorption capacity of the resin was found, which implied that the APTZ-PS resin was suitable for the efficient removal of heavy metal ions from aqueous solution. Copyright © 2014 Elsevier B.V. All rights reserved.

The coordination- and photochemistry of copper(i) complexes: variation of N^N ligands from imidazole to tetrazole.

PubMed

Bergmann, Larissa; Braun, Carolin; Nieger, Martin; Bräse, Stefan

2018-01-02

The prediction of coordination modes is of high importance when structure-property relationships are discussed. Herein, the coordination chemistry of copper(i) with pyridine-amines with a varying number of coordinating N-atoms, namely pyridine-benzimidazole, -triazole and -tetrazole, or their deprotonated analogues, and different phosphines was systematically studied and the photoluminescence properties of all synthesized complexes examined and related to DFT data. Each complex was characterized by single-crystal X-ray analysis and elemental analysis, and a set of prediction rules derived for the coordination chemistry of copper(i) with these ligands. A mononuclear cationic coordination motif was found for PPh 3 or DPEPhos with all N^N ligands, which exhibits blue to green luminescence of MLCT character d(Cu) → π*(pyridine-amine ligand) with quantum yields up to 46%. With the deprotonated N^N ligands, mononuclear neutral complexes were only expected with DPEPhos. The emission's nature of this complex type is strongly dependent on the electronic effects of the N^N ligand and was characterized as (ML + IL)CT transition. In contrast to the high quantum yields up to 78% for the tetrazolate complexes (as reported before), the triazolate and imidazolate based complexes show much lower emission efficiencies below 10%. Besides the mononuclear copper(i) complexes, cluster-type complexes were obtained, which show moderate luminescence in the blue to green region of the visible spectrum (469-505 nm).

Combinatorial Effects of Aromatic 1,3-Disubstituted Ureas and Fluoride on In vitro Inhibition of Streptococcus mutans Biofilm Formation.

PubMed

Kaur, Gurmeet; Balamurugan, P; Uma Maheswari, C; Anitha, A; Princy, S Adline

2016-01-01

Dental caries occur as a result of disequilibrium between acid producing pathogenic bacteria and alkali generating commensal bacteria within a dental biofilm (dental plaque). Streptococcus mutans has been reported as a primary cariogenic pathogen associated with dental caries. Emergence of multidrug resistant as well as fluoride resistant strains of S. mutans due to over use of various antibiotics are a rising problem and prompted the researchers worldwide to search for alternative therapies. In this perspective, the present study was aimed to screen selective inhibitors against ComA, a bacteriocin associated ABC transporter, involved in the quorum sensing of S. mutans. In light of our present in silico findings, 1,3-disubstituted urea derivatives which had better affinity to ComA were chemically synthesized in the present study for in vitro evaluation of S. mutans biofilm inhibition. The results revealed that 1,3-disubstituted urea derivatives showed good biofilm inhibition. In addition, synthesized compounds exhibited potent synergy with a very low concentration of fluoride (31.25-62.5 ppm) in inhibiting the biofilm formation of S. mutans without affecting the bacterial growth. Further, the results were supported by confocal laser scanning microscopy. On the whole, from our experimental results we conclude that the combinatorial application of fluoride and disubstituted ureas has a potential synergistic effect which has a promising approach in combating multidrug resistant and fluoride resistant S. mutans in dental caries management.

A Novel High-Density Phase and Amorphization of Nitrogen-Rich 1H-Tetrazole (CH2N4) under High Pressure

PubMed Central

Li, Wenbo; Huang, Xiaoli; Bao, Kuo; Zhao, Zhonglong; Huang, Yanping; Wang, Lu; Wu, Gang; Zhou, Bo; Duan, Defang; Li, Fangfei; Zhou, Qiang; Liu, Bingbing; Cui, Tian

2017-01-01

The high-pressure behaviors of nitrogen-rich 1H-tetrazole (CH2N4) have been investigated by in situ synchrotron X-ray diffraction (XRD) and Raman scattering up to 75 GPa. A first crystalline-to-crystalline phase transition is observed and identified above ~3 GPa with a large volume collapse (∼18% at 4.4 GPa) from phase I to phase II. The new phase II forms a dimer-like structure, belonging to P1 space group. Then, a crystalline-to-amorphous phase transition takes place over a large pressure range of 13.8 to 50 GPa, which is accompanied by an interphase region approaching paracrystalline state. When decompression from 75 GPa to ambient conditions, the final product keeps an irreversible amorphous state. Our ultraviolet (UV) absorption spectrum suggests the final product exhibits an increase in molecular conjugation. PMID:28218236

Synthesis and characterization of a multifunctional inorganic-organic hybrid mixed-valence copper(I/II) coordination polymer: {[CuCN][Cu(isonic)2]}n

NASA Astrophysics Data System (ADS)

Liu, Dong-Sheng; Chen, Wen-Tong; Ye, Guang-Ming; Zhang, Jing; Sui, Yan

2017-12-01

A new multifunctional mixed-valence copper(I/II) coordination polymer, {[CuCN][Cu(isonic)2]}n(1) (Hisonic = isonicotinic acid), was synthesized by treating isonicotinic acid and 5-amino-tetrazolate (Hatz = 5-amino-tetrazolate) with copper(II) salts under hydrothermal conditions, and characterized by elemental analysis, infrared spectroscopy, and single crystal X-ray diffraction, respectively. The X-ray diffraction analysis reveals that compound exhibit noncentrosymmetric polar packing arrangement. It is three-dimensional (3D) framework with (3,5)-connected 'seh-3' topological network constructed from metal organic framework {[Cu(isonic)2]}n and the inorganic linear chain{Cu(CN)}n subunits. A remarkable feature of 1 is the rhombic open channels that are occupied by a linear chain of {Cu(CN)}n. Impressively compound 1 displays not only a second harmonic generation (SHG) response, but also a ferroelectric behavior and magnetic properties.

Substituted 3-((Z)-2-(4-nitrophenyl)-2-(1H-tetrazol-5-yl) vinyl)-4H-chromen-4-ones as novel anti-MRSA agents: synthesis, SAR, and in-vitro assessment.

PubMed

Diwakar, Santosh D; Bhagwat, Sachin S; Shingare, Murlidhar S; Gill, Charansing H

2008-08-15

In search for a new antibacterial agent with improved antimicrobial spectrum and potency, we designed and synthesized a series of novel 3-((Z)-2-(4-nitrophenyl)-2-(1H-tetrazol-5-yl) vinyl)-4H-chromen-4-ones 7a-h by convergent synthesis approach. All the synthesized compounds were assayed for their in-vitro antibacterial activities against gram-negative and gram-positive bacteria. The preliminary structure-activity relationship, to elucidate the essential structure requirements for the antimicrobial activity that results into anti-MRSA (methicillin-resistant S. aureus) potential, has been described. Amongst the synthesized compounds 7d, 7e, 7f and 7h were found to possess activity against methicillin-resistant S. aureus in addition to the activity against other bacterial strains such as E. faecalis, S. pneumoniae, and E. coli.

N-Acetonitrile Functionalized Nitropyrazoles: Precursors to Insensitive Asymmetric N-Methylene-C Linked Azoles.

PubMed

Kumar, Dheeraj; Imler, Gregory H; Parrish, Damon A; Shreeve, Jean'ne M

2017-06-12

Properties of energetic compounds obtained by linking energetic pyrazoles to tetrazoles by means of N-methylene-C bridges can be fine-tuned. Reactions of pyrazole derivatives with chloroacetonitrile followed by conversion of the cyano group to tetrazole using click reactions in the presence of zinc chloride result in asymmetric N-methylene-C bridged azole-based energetic compounds. All the compounds were thoroughly characterized by IR and NMR [ 1 H, 13 C { 1 H}, 15 N] spectroscopy, elemental analysis, and differential scanning calorimetry (DSC), and for two compounds, further supported by single-crystal X-ray diffraction studies. Heats of formation and detonation performances were calculated using Gaussian 03 and EXPLO5 v6.01 programs, respectively. Initial studies show that this new approach is promising for synthesizing less sensitive energetic compounds with fine-tuned properties. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Novel High-Density Phase and Amorphization of Nitrogen-Rich 1H-Tetrazole (CH2N4) under High Pressure.

PubMed

Li, Wenbo; Huang, Xiaoli; Bao, Kuo; Zhao, Zhonglong; Huang, Yanping; Wang, Lu; Wu, Gang; Zhou, Bo; Duan, Defang; Li, Fangfei; Zhou, Qiang; Liu, Bingbing; Cui, Tian

2017-02-20

The high-pressure behaviors of nitrogen-rich 1H-tetrazole (CH 2 N 4 ) have been investigated by in situ synchrotron X-ray diffraction (XRD) and Raman scattering up to 75 GPa. A first crystalline-to-crystalline phase transition is observed and identified above ~3 GPa with a large volume collapse (∼18% at 4.4 GPa) from phase I to phase II. The new phase II forms a dimer-like structure, belonging to P1 space group. Then, a crystalline-to-amorphous phase transition takes place over a large pressure range of 13.8 to 50 GPa, which is accompanied by an interphase region approaching paracrystalline state. When decompression from 75 GPa to ambient conditions, the final product keeps an irreversible amorphous state. Our ultraviolet (UV) absorption spectrum suggests the final product exhibits an increase in molecular conjugation.

Synthesis, characterization and theoretical studies of 5-(benzylthio)-1-cylopentyl-1H-tetrazole

NASA Astrophysics Data System (ADS)

Saglam, S.; Disli, A.; Erdogdu, Y.; Marchewka, M. K.; Kanagathara, N.; Bay, B.; Güllüoğlu, M. T.

2015-01-01

In this study, 5-(benzylthio)-1-cylopentyl-1H-tetrazole (5B1C1HT) have been synthesized. Boiling points of the obtained compound have been determined and it has been characterized by FT-IR, 1H NMR, 13C-APT and LC-MS spectroscopy techniques. The FT-IR, 1H NMR and 13C-APT spectral measurements of the 5B1C1HT compound and complete assignment of the vibrational bands observed in spectra has been discussed. The spectra were interpreted with the aid of normal coordinate analysis following full structure optimization and force field calculations based on Density Functional Theory (DFT) at 6-311++G**, cc-pVDZ and cc-pVTZ basis sets. The optimized geometry with 6-311++G** basis sets were used to determine the total energy distribution, harmonic vibrational frequencies, IR intensities.

Synthesis, characterization and theoretical studies of 5-(benzylthio)-1-cylopentyl-1H-tetrazole.

PubMed

Saglam, S; Disli, A; Erdogdu, Y; Marchewka, M K; Kanagathara, N; Bay, B; Güllüoğlu, M T

2015-01-25

In this study, 5-(benzylthio)-1-cylopentyl-1H-tetrazole (5B1C1HT) have been synthesized. Boiling points of the obtained compound have been determined and it has been characterized by FT-IR, (1)H NMR, (13)C-APT and LC-MS spectroscopy techniques. The FT-IR, (1)H NMR and (13)C-APT spectral measurements of the 5B1C1HT compound and complete assignment of the vibrational bands observed in spectra has been discussed. The spectra were interpreted with the aid of normal coordinate analysis following full structure optimization and force field calculations based on Density Functional Theory (DFT) at 6-311++G(**), cc-pVDZ and cc-pVTZ basis sets. The optimized geometry with 6-311++G(**) basis sets were used to determine the total energy distribution, harmonic vibrational frequencies, IR intensities. Copyright © 2014 Elsevier B.V. All rights reserved.

A Bioinspired Catalytic Aerobic Oxidative C–H Functionalization of Primary Aliphatic Amines: Synthesis of 1,2-Disubstituted Benzimidazoles

PubMed Central

Nguyen, Khac Minh Huy; Largeron, Martine

2015-01-01

Aerobic oxidative C–H functionalization of primary aliphatic amines has been accomplished with a biomimetic cooperative catalytic system to furnish 1,2-disubstituted benzimidazoles that play an important role as drug discovery targets. This one-pot atom-economical multistep process, which proceeds under mild conditions, with ambient air and equimolar amounts of each coupling partner, constitutes a convenient environmentally friendly strategy to functionalize non-activated aliphatic amines that remain challenging substrates for non-enzymatic catalytic aerobic systems. PMID:26206475

Design, Synthesis, and Evaluation of Novel 2,6-Disubstituted Phenol Derivatives as General Anesthetics.

PubMed

Qin, Linlin; Ren, Lei; Wan, Songlin; Liu, Guoliang; Luo, Xinfeng; Liu, Zhenhong; Li, Fangqiong; Yu, Yan; Liu, Jianyu; Wei, Yonggang

2017-05-11

A novel series of optically active 2,6-disubstituted alkylphenols with improved anesthetic profiles compared to widely used propofol were synthesized. The incorporation of the cyclopropyl group not only increased the steric effect but also introduced stereoselective effects over their anesthetic properties. Compounds 1, 2, and 6 were selected as potential candidates for further preclinical development including studies of their water-soluble prodrugs. Clinical studies of candidate compound 6 (Haisco HSK3486) as a general anesthetic are being performed in Australia and China.

Efficient and highly enantioselective construction of trifluoromethylated quaternary stereogenic centers via high-pressure mediated organocatalytic conjugate addition of nitromethane to β,β-disubstituted enones.

PubMed

Kwiatkowski, Piotr; Cholewiak, Agnieszka; Kasztelan, Adrian

2014-11-21

A very effective high-pressure-induced acceleration of asymmetric organocatalytic conjugate addition of nitromethane to sterically congested β,β-disubstituted β-CF3 enones has been developed. A combination of pressure (8-10 kbar) and noncovalent catalysis with low-loading of chiral tertiary amine-thioureas (0.5-3 mol %) is shown to provide very efficient access to a wide range of γ-nitroketones containing trifluoromethylated all-carbon quaternary stereogenic centers in the β-position (80-97%, 92-98% ee).

Gold(I)-Catalysed Hydroarylation of 1,3-Disubstituted Allenes with Efficient Axial-to-Point Chirality Transfer.

PubMed

Sutherland, Daniel R; Kinsman, Luke; Angiolini, Stuart M; Rosair, Georgina M; Lee, Ai-Lan

2018-05-11

Hydroarylation of enantioenriched 1,3-disubstituted allenes has the potential to proceed with axial-to-point chirality transfer to yield enantioenriched allylated (hetero)aryl compounds. However, the gold-catalysed intermolecular reaction was previously reported to occur with no chirality transfer owing to competing allene racemisation. Herein, we describe the development of the first intermolecular hydroarylations of allenes to proceed with efficient chirality transfer and summarise some of the key criteria for achieving high regio- and stereoselectivity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Crystal structures of (Z)-5-[2-(benzo[b]thio-phen-2-yl)-1-(3,5-di-meth-oxy-phen-yl)ethen-yl]-1H-tetra-zole and (Z)-5-[2-(benzo[b]thio-phen-3-yl)-1-(3,4,5-tri-meth-oxy-phen-yl)ethen-yl]-1H-tetra-zole.

PubMed

Penthala, Narsimha Reddy; Yadlapalli, Jaishankar K B; Parkin, Sean; Crooks, Peter A

2016-05-01

(Z)-5-[2-(Benzo[b]thio-phen-2-yl)-1-(3,5-di-meth-oxy-phen-yl)ethen-yl]-1H-tetrazole methanol monosolvate, C19H16N4O2S·CH3OH, (I), was prepared by the reaction of (Z)-3-(benzo[b]thio-phen-2-yl)-2-(3,5-di-meth-oxy-phen-yl)acrylo-nitrile with tri-butyl-tin azide via a [3 + 2]cyclo-addition azide condensation reaction. The structurally related compound (Z)-5-[2-(benzo[b]thio-phen-3-yl)-1-(3,4,5-tri-meth-oxy-phen-yl)ethen-yl]-1H-tetra-zole, C20H18N4O3S, (II), was prepared by the reaction of (Z)-3-(benzo[b]thio-phen-3-yl)-2-(3,4,5-tri-meth-oxy-phen-yl)acrylo-nitrile with tri-butyl-tin azide. Crystals of (I) have two mol-ecules in the asymmetric unit (Z' = 2), whereas crystals of (II) have Z' = 1. The benzo-thio-phene rings in (I) and (II) are almost planar, with r.m.s deviations from the mean plane of 0.0084 and 0.0037 Å in (I) and 0.0084 Å in (II). The tetra-zole rings of (I) and (II) make dihedral angles with the mean planes of the benzo-thio-phene rings of 88.81 (13) and 88.92 (13)° in (I), and 60.94 (6)° in (II). The di-meth-oxy-phenyl and tri-meth-oxy-phenyl rings make dihedral angles with the benzo-thio-phene rings of 23.91 (8) and 24.99 (8)° in (I) and 84.47 (3)° in (II). In both structures, mol-ecules are linked into hydrogen-bonded chains. In (I), these chains involve both tetra-zole and methanol, and are parallel to the b axis. In (II), mol-ecules are linked into chains parallel to the a axis by N-H⋯N hydrogen bonds between adjacent tetra-zole rings.

Synthesis, antimycobacterial and cytotoxic activity of α,β-unsaturated amides and 2,4-disubstituted oxazoline derivatives.

PubMed

Avalos-Alanís, Francisco G; Hernández-Fernández, Eugenio; Carranza-Rosales, Pilar; López-Cortina, Susana; Hernández-Fernández, Jorge; Ordóñez, Mario; Guzmán-Delgado, Nancy E; Morales-Vargas, Alejandro; Velázquez-Moreno, Víctor M; Santiago-Mauricio, María G

2017-02-15

The synthesis of six α,β,-unsaturated amides and six 2,4-disubstituted oxazolines derivatives and their evaluation against two Mycobacterium tuberculosis strains (sensitive H37Rv and a resistant clinical isolate) is reported. 2,4-Disubstituted oxazolines (S)-3b,d,e were the most active in the sensitive strain with a MIC of 14.2, 13.6 and 10.8μM, respectively, and the compounds (S)-3d,f were the most active against resistant strain with a MIC of 6.8 and 7.4μM. The ex-vivo evaluation of hepatotoxicity on precision-cut rat liver slices was also tested for the α,β-unsaturated amides (S)-2b and (S)-2d,f and for the oxazolines (S)-3b and (S)-3d,f at different concentrations (5, 15 and 30μg/mL). The results indicate that these compounds possess promising antimycobacterial activity and at the same time are not hepatotoxic. These findings open the possibility for development of new drugs against tuberculosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Metallosupramolecular Architectures Formed with Ferrocene-Linked Bis-Bidentate Ligands: Synthesis, Structures, and Electrochemical Studies.

PubMed

Findlay, James A; McAdam, C John; Sutton, Joshua J; Preston, Dan; Gordon, Keith C; Crowley, James D

2018-04-02

The self-assembly of ligands of different geometries with metal ions gives rise to metallosupramolecular architectures of differing structural types. The rotational flexibility of ferrocene allows for conformational diversity, and, as such, self-assembly processes with 1,1'-disubstituted ferrocene ligands could lead to a variety of interesting architectures. Herein, we report a small family of three bis-bidentate 1,1'-disubstituted ferrocene ligands, functionalized with either 2,2'-bipyridine or 2-pyridyl-1,2,3-triazole chelating units. The self-assembly of these ligands with the (usually) four-coordinate, diamagnetic metal ions Cu(I), Ag(I), and Pd(II) was examined using a range of techniques including 1 H and DOSY NMR spectroscopies, high-resolution electrospray ionization mass spectrometry, X-ray crystallography, and density functional theory calculations. Additionally, the electrochemical properties of these redox-active metallosupramolecular assemblies were examined using cyclic voltammetry and differential pulse voltammetry. The copper(I) complexes of the 1,1'-disubstituted ferrocene ligands were found to be coordination polymers, while the silver(I) and palladium(II) complexes formed discrete [1 + 1] or [2 + 2] metallomacrocyclic architectures.

Synthesis of 2-Aryl- and 2-Vinylpyrrolidines via Copper-Catalyzed Coupling of Styrenes and Dienes with Potassium β-Aminoethyl Trifluoroborates.

PubMed

Um, Chanchamnan; Chemler, Sherry R

2016-05-20

2-Arylpyrrolidines occur frequently in bioactive compounds, and thus, methods to access them from readily available reagents are valuable. We report a copper-catalyzed intermolecular carboamination of vinylarenes with potassium N-carbamoyl-β-aminoethyltrifluoroborates. The reaction occurs with terminal, 1,2-disubstituted, and 1,1-disubstituted vinylarenes bearing a number of functional groups. 1,3-Dienes are also good substrates, and their reactions give 2-vinylpyrrolidines. Radical clock mechanistic experiments are consistent with the presence of carbon radical intermediates and do not support participation of carbocations.

Gold-catalysed oxyarylation of styrenes and mono- and gem-disubstituted olefins facilitated by an iodine(III) oxidant.

PubMed

Ball, Liam T; Lloyd-Jones, Guy C; Russell, Christopher A

2012-03-05

1-Hydroxy-1,2-benziodoxol-3(1H)-one (IBA) is an efficient terminal oxidant for gold-catalysed, three-component oxyarylation reactions. The use of this iodine(III) reagent expands the scope of oxyarylation to include styrenes and gem-disubstituted olefins, substrates that are incompatible with the previously reported Selectfluor-based methodology. Diverse arylsilane coupling partners can be employed, and in benzotrifluoride, homocoupling is substantially reduced. In addition, the IBA-derived co-products can be recovered and recycled. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Use of 2,5-dimethyl-2,5-hexane diamine as a curing agent for epoxy resins

DOEpatents

Rinde, J.A.; Newey, H.A.

1981-02-24

Primary diamines are disclosed of the formula shown in a diagram wherein R is a straight chain saturated hydrocarbon of 2 to 4 carbons, a disubstituted benzene ring, or disubstituted dibenzomethane for use as a curing agent for epoxy resins. These curing agents can be used to form epoxy resin mixtures useful in filament winding and pre-impregnated fiber molding and in formulating film adhesives, powder coatings and molding powders. The epoxy mixtures form for such uses as room temperature non-reacting, intermediate stable state which has a latent cross-linking capability.

Use of 2,5-dimethyl-2,5-hexane diamine as a curing agent for epoxy resins

DOEpatents

Rinde, James A. [Livermore, CA; Newey, Herbert A. [Lafayette, CA

1981-02-24

Primary diamines of the formula ##STR1## wherein R is a straight chain saturated hydrocarbon of 2 to 4 carbons, a disubstituted benzene ring, or disubstituted dibenzo methane for use as a curing agent for epoxy resins. These curing agents can be used to form epoxy resin mixtures useful in filament winding and pre-impregnated fiber molding and in formulating film adhesives, powder coatings and molding powders. The epoxy mixtures form for such uses as room temperature non-reacting, intermediate stable state which has a latent cross-linking capability.

Synthesis and antitumor screening of new 1,7-diphenyl-3-(1,3-disubstituted-1H-pyrazole-4-carbonyl)-[1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones.

PubMed

Shawali, Ahmad S; Sherif, Sherif M; Darwish, Manal A A; El-merzabani, Mahmoud M

2010-01-01

A new series of 3-(1,3-disubstituted-1H-pyrazole-4-carbonyl)-1,7-diphenyl-[1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones 4 was prepared by reaction of the enaminone 2 with hydrazonoyl halides 3. The preliminary screening for antitumor activity of the synthesized compounds was carried out against Ehrlich Ascites Carcinoma tumor cells. The results revealed that the studied compounds 4 have low or no antitumor activity towards EAC tumor cells.

Enantioselective synthesis of 2,2-disubstituted terminal epoxides via catalytic asymmetric Corey-Chaykovsky epoxidation of ketones.

PubMed

Sone, Toshihiko; Yamaguchi, Akitake; Matsunaga, Shigeki; Shibasaki, Masakatsu

2012-02-07

Catalytic asymmetric Corey-Chaykovsky epoxidation of various ketones with dimethyloxosulfonium methylide using a heterobimetallic La-Li(3)-BINOL complex (LLB) is described. The reaction proceeded smoothly at room temperature in the presence of achiral phosphine oxide additives, and 2,2-disubstituted terminal epoxides were obtained in high enantioselectivity (97%-91% ee) and yield ( > 99%-88%) from a broad range of methyl ketones with 1-5 mol% catalyst loading. Enantioselectivity was strongly dependent on the steric hindrance, and other ketones, such as ethyl ketones and propyl ketones resulted in slightly lower enantioselectivity (88%-67% ee).

MOF-253-Pd(OAc) 2 : a recyclable MOF for transition-metal catalysis in water

DOE PAGES

Van Zeeland, Ryan; Li, Xinle; Huang, Wenyu; ...

2016-06-06

We report palladium(II)-functionalized MOF-253 (MOF-253-Pd(OAc) 2) as a recyclable catalyst to form all-carbon quaternary centers via conjugate additions of arylboronic acids to β,β-disubstituted enones in aqueous media. We demonstrate MOF-253-Pd(OAc) 2 can be reused 8 times to form ketone products in yields above 75% while maintaining its crystallinity. Additions of a range of stereoelectronically diverse arylboronic acids to a variety of β,β-disubstituted enones catalyzed by MOF-253-Pd(OAc) 2 occur in modest-to-high yields (34–95%).

Consistent assignment of the vibrations of symmetric and asymmetric meta-disubstituted benzenes

NASA Astrophysics Data System (ADS)

Kemp, David J.; Tuttle, William D.; Jones, Florence M. S.; Gardner, Adrian M.; Andrejeva, Anna; Wakefield, Jonathan C. A.; Wright, Timothy G.

2018-04-01

The assignment of vibrational structure in spectra gives valuable insights into geometric and electronic structure changes upon electronic excitation or ionization; particularly when such information is available for families of molecules. We give a description of the phenyl-ring-localized vibrational modes of the ground (S0) electronic states of sets of meta-disubstituted benzene molecules including both symmetrically- and asymmetrically-substituted cases. As in our earlier work on monosubstituted benzenes (Gardner and Wright, 2011), para-disubstituted benzenes (Andrejeva et al., 2016), and ortho-disubstituted benzenes (Tuttle et al., 2018), we conclude that the use of the commonly-used Wilson or Varsányi mode labels, which are based on the vibrational motions of benzene itself, is misleading and ambiguous. Instead, we label the phenyl-ring-localized modes consistently based upon the Mulliken (Herzberg) method for the modes of meta-difluorobenzene (mDFB) under Cs symmetry, since we wish the labelling scheme to cover both symmetrically- and asymmetrically-substituted molecules. By studying the vibrational wavenumbers obtained from the same force-field while varying the mass of the substituent, we are able to follow the evolving modes across a wide range of molecules and hence provide consistent assignments. We assign the vibrations of the following sets of molecules: the symmetric meta-dihalobenzenes, meta-xylene and resorcinol (meta-dihydroxybenzene); and the asymmetric meta-dihalobenzenes, meta-halotoluenes, meta-halophenols and meta-cresol. In the symmetrically-substituted species, we find two pairs of in-phase and out-of-phase carbon-substituent stretches, and this motion persists in asymmetrically-substituted molecules for heavier substituents; however, when at least one of the substituents is light, then we find that these evolve into localized carbon-substituent stretches.

Dietary alkaloid sequestration in a poison frog: an experimental test of alkaloid uptake in Melanophryniscus stelzneri (Bufonidae).

PubMed

Hantak, Maggie M; Grant, Taran; Reinsch, Sherri; McGinnity, Dale; Loring, Marjorie; Toyooka, Naoki; Saporito, Ralph A

2013-12-01

Several lineages of brightly colored anurans independently evolved the ability to secrete alkaloid-containing defensive chemicals from granular glands in the skin. These species, collectively referred to as 'poison frogs,' form a polyphyletic assemblage that includes some species of Dendrobatidae, Mantellidae, Myobatrachidae, Bufonidae, and Eleutherodactylidae. The ability to sequester alkaloids from dietary arthropods has been demonstrated experimentally in most poison frog lineages but not in bufonid or eleutherodactylid poison frogs. As with other poison frogs, species of the genus Melanophryniscus (Bufonidae) consume large numbers of mites and ants, suggesting they might also sequester defensive alkaloids from dietary sources. To test this hypothesis, fruit flies dusted with alkaloid/nutritional supplement powder were fed to individual Melanophryniscus stelzneri in two experiments. In the first experiment, the alkaloids 5,8-disubstituted indolizidine 235B' and decahydroquinoline were administered to three individuals for 104 days. In the second experiment, the alkaloids 3,5-disubstituted indolizidine 239Q and decahydroquinoline were given to three frogs for 153 days. Control frogs were fed fruit flies dusted only with nutritional supplement. Gas chromatography/mass spectrometry analyses revealed that skin secretions of all experimental frogs contained alkaloids, whereas those of all control frogs lacked alkaloids. Uptake of decahydroquinoline was greater than uptake of 5,8-disubstituted indolizidine, and uptake of 3,5-disubstituted indolizidine was greater than uptake of decahydroquinoline, suggesting greater uptake efficiency of certain alkaloids. Frogs in the second experiment accumulated a greater amount of alkaloid, which corresponds to the longer duration and greater number of alkaloid-dusted fruit flies that were consumed. These findings provide the first experimental evidence that bufonid poison frogs sequester alkaloid-based defenses from dietary sources.

Insights into the Quorum Sensing Regulon of the Acidophilic Acidithiobacillus ferrooxidans Revealed by Transcriptomic in the Presence of an Acyl Homoserine Lactone Superagonist Analog

PubMed Central

Mamani, Sigde; Moinier, Danielle; Denis, Yann; Soulère, Laurent; Queneau, Yves; Talla, Emmanuel; Bonnefoy, Violaine; Guiliani, Nicolas

2016-01-01

While a functional quorum sensing system has been identified in the acidophilic chemolithoautotrophic Acidithiobacillus ferrooxidans ATCC 23270T and shown to modulate cell adhesion to solid substrates, nothing is known about the genes it regulates. To address the question of how quorum sensing controls biofilm formation in A. ferrooxidansT, the transcriptome of this organism in conditions in which quorum sensing response is stimulated by a synthetic superagonist AHL (N-acyl homoserine lactones) analog has been studied. First, the effect on biofilm formation of a synthetic AHL tetrazolic analog, tetrazole 9c, known for its agonistic QS activity, was assessed by fluorescence and electron microscopy. A fast adherence of A. ferrooxidansT cells on sulfur coupons was observed. Then, tetrazole 9c was used in DNA microarray experiments that allowed the identification of genes regulated by quorum sensing signaling, and more particularly, those involved in early biofilm formation. Interestingly, afeI gene, encoding the AHL synthase, but not the A. ferrooxidans quorum sensing transcriptional regulator AfeR encoding gene, was shown to be regulated by quorum sensing. Data indicated that quorum sensing network represents at least 4.5% (141 genes) of the ATCC 23270T genome of which 42.5% (60 genes) are related to biofilm formation. Finally, AfeR was shown to bind specifically to the regulatory region of the afeI gene at the level of the palindromic sequence predicted to be the AfeR binding site. Our results give new insights on the response of A. ferrooxidans to quorum sensing and on biofilm biogenesis. PMID:27683573

Reassessment of the Unique Mode of Binding between Angiotensin II Type 1 Receptor and Their Blockers

PubMed Central

Matsuo, Yoshino; Saku, Keijiro; Karnik, Sadashiva S.

2013-01-01

While the molecular structures of angiotensin II (Ang II) type 1 (AT1) receptor blockers (ARBs) are very similar, they are also slightly different. Although each ARB has been shown to exhibit a unique mode of binding to AT1 receptor, different positions of the AT1 receptor have been analyzed and computational modeling has been performed using different crystal structures for the receptor as a template and different kinds of software. Therefore, we systematically analyzed the critical positions of the AT1 receptor, Tyr113, Tyr184, Lys199, His256 and Gln257 using a mutagenesis study, and subsequently performed computational modeling of the binding of ARBs to AT1 receptor using CXCR4 receptor as a new template and a single version of software. The interactions between Tyr113 in the AT1 receptor and the hydroxyl group of olmesartan, between Lys199 and carboxyl or tetrazole groups, and between His256 or Gln257 and the tetrazole group were studied. The common structure, a tetrazole group, of most ARBs similarly bind to Lys199, His256 and Gln257 of AT1 receptor. Lys199 in the AT1 receptor binds to the carboxyl group of EXP3174, candesartan and azilsartan, whereas oxygen in the amidecarbonyl group of valsartan may bind to Lys199. The benzimidazole portion of telmisartan may bind to a lipophilic pocket that includes Tyr113. On the other hand, the n-butyl group of irbesartan may bind to Tyr113. In conclusion, we confirmed that the slightly different structures of ARBs may be critical for binding to AT1 receptor and for the formation of unique modes of binding. PMID:24260317

Insights into the Quorum Sensing Regulon of the Acidophilic Acidithiobacillus ferrooxidans Revealed by Transcriptomic in the Presence of an Acyl Homoserine Lactone Superagonist Analog.

PubMed

Mamani, Sigde; Moinier, Danielle; Denis, Yann; Soulère, Laurent; Queneau, Yves; Talla, Emmanuel; Bonnefoy, Violaine; Guiliani, Nicolas

2016-01-01

While a functional quorum sensing system has been identified in the acidophilic chemolithoautotrophic Acidithiobacillus ferrooxidans ATCC 23270(T) and shown to modulate cell adhesion to solid substrates, nothing is known about the genes it regulates. To address the question of how quorum sensing controls biofilm formation in A. ferrooxidans (T), the transcriptome of this organism in conditions in which quorum sensing response is stimulated by a synthetic superagonist AHL (N-acyl homoserine lactones) analog has been studied. First, the effect on biofilm formation of a synthetic AHL tetrazolic analog, tetrazole 9c, known for its agonistic QS activity, was assessed by fluorescence and electron microscopy. A fast adherence of A. ferrooxidans (T) cells on sulfur coupons was observed. Then, tetrazole 9c was used in DNA microarray experiments that allowed the identification of genes regulated by quorum sensing signaling, and more particularly, those involved in early biofilm formation. Interestingly, afeI gene, encoding the AHL synthase, but not the A. ferrooxidans quorum sensing transcriptional regulator AfeR encoding gene, was shown to be regulated by quorum sensing. Data indicated that quorum sensing network represents at least 4.5% (141 genes) of the ATCC 23270(T) genome of which 42.5% (60 genes) are related to biofilm formation. Finally, AfeR was shown to bind specifically to the regulatory region of the afeI gene at the level of the palindromic sequence predicted to be the AfeR binding site. Our results give new insights on the response of A. ferrooxidans to quorum sensing and on biofilm biogenesis.

Construction of three lanthanide metal-organic frameworks: Synthesis, structure, magnetic properties and highly selective sensing of metal ions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Xiu-Mei, E-mail: zhangxiumeilb@126.com; Li, Peng; Gao, Wei

Three lanthanide metal-organic frameworks (Ln-MOFs), [Ln(TZI)(H{sub 2}O){sub 4}]·3H{sub 2}O (Ln=Gd (1) and Tb (2) and Dy (3), H{sub 3}TZI=5-(1H-tetrazol-5-yl)isophthalic acid), have been synthesized under hydrothermal conditions. Single crystal X-ray diffraction reveals that 1–3 are isostructural and display a 1D double chain based on dinuclear motifs with (μ-COO){sub 2} double bridges. Magnetic studies indicate antiferromagnetic interactions in 1, ferromagnetic interactions in 2 and 3. Furthermore, compound 3 displays a slow relaxation behavior. Compound 2 exhibits intense characteristic green emission of Tb(III) ions in the solid state, which can be observed by the naked eye under UV light. Interestingly, 2 can selectivelymore » sense Pb{sup 2+} and Fe{sup 3+} ions through luminescence enhancement and quenching, respectively. The luminescence quenching mechanisms have been investigated in detail. The study on luminescence Ln-MOFs as a probe for sensing Pb{sup 2+} and Fe{sup 3+} ions is exceedingly rare example. - Graphical abstract: Three Ln-MOFs were successfully synthesized using a 5-(1H-tetrazol-5-yl)isophthalic acid ligand. They displays different magnetic behavior. Especially, the Dy(III) compound slow relaxation behavior. Interestingly, the Tb(III) compound can selectively sense Pb{sup 2+} and Fe{sup 3+} ions through luminescence enhancement and quenching, respectively. - Highlights: • Three Ln-MOFs with tetrazolate dicarboxylate ligand. • Dy(III) compound displays slow relaxation behavior. • The Tb(III) compound shows highly selective luminescence sensing of the Fe{sup 3+} and Pb{sup 2+} ions.« less

A one-dimensional zinc(II) coordination polymer with a three-dimensional supramolecular architecture incorporating 1-[(1H-benzimidazol-2-yl)methyl]-1H-tetrazole and adipate.

PubMed

Liu, Chun Li; Huang, Qiu Ying; Meng, Xiang Ru

2016-12-01

The synthesis of coordination polymers or metal-organic frameworks (MOFs) has attracted considerable interest owing to the interesting structures and potential applications of these compounds. It is still a challenge to predict the exact structures and compositions of the final products. A new one-dimensional coordination polymer, catena-poly[[[bis{1-[(1H-benzimidazol-2-yl)methyl]-1H-tetrazole-κN 3 }zinc(II)]-μ-hexane-1,6-dicarboxylato-κ 4 O 1 ,O 1' :O 6 ,O 6' ] monohydrate], {[Zn(C 6 H 8 O 4 )(C 9 H 8 N 6 ) 2 ]·H 2 O} n , has been synthesized by the reaction of Zn(Ac) 2 (Ac is acetate) with 1-[(1H-benzimidazol-2-yl)methyl]-1H-tetrazole (bimt) and adipic acid (H 2 adi) at room temperature. In the polymer, each Zn II ion exhibits an irregular octahedral ZnN 2 O 4 coordination geometry and is coordinated by two N atoms from two symmetry-related bimt ligands and four O atoms from two symmetry-related dianionic adipate ligands. Zn II ions are connected by adipate ligands into a one-dimensional chain which runs parallel to the c axis. The bimt ligands coordinate to the Zn II ions in a monodentate mode on both sides of the main chain. In the crystal, the one-dimensional chains are further connected through N-H...O hydrogen bonds, leading to a three-dimensional supramolecular architecture. In addition, the title polymer exhibits fluorescence, with emissions at 334 and 350 nm in the solid state at room temperature.

Synthesis of framework isomer MOFs containing zinc and 4-tetrazolyl benzenecarboxylic acid via a structure directing solvothermal approach

DOE PAGES

Ordonez, Carlos; Kinnibrugh, Tiffany L.; Xu, Hongwu; ...

2015-04-02

The solvothermal synthesis of framework isomers was carried out using the hybrid carboxylate and tetrazolate functional ligand, 4-tetrazolyl benzenecarboxylic acid (H₂TBC, TBC = 4-tetrazolyl benzenecarboxylate) and zinc. H₂TBC was also synthesized with the solvothermal approach, and is referred herein as structure 1. Using single-crystal X-ray diffraction, we found that the tetrazolate groups of TBC show an unusual “opposite-on” coordination mode with zinc. Three previously characterized metal-organic frameworks (MOFs) were obtained by systematically changing the solvents of the H₂TBC-Zn reaction, (1) ZnTBC, 2, which has a non-porous structure; (2) Zn₂(TBC)₂(H2O), 3, which has an amphiphilic pore structure and (3) Zn₂(TBC)₂{guest}, 4,more » which is porous and has channels containing uncoordinated N heteroatoms. Fluorescence spectra of 4 reveal a strong blue emission mainly from the TBC ligands.« less

Nitrogen-rich salts based on the energetic [monoaquabis(N,N-bis(1H-tetrazol-5-yl)amine)-zinc(II)] anion: a promising design in the development of new energetic materials.

PubMed

Li, Fugang; Bi, Yangang; Zhao, Wenyuan; Zhang, Tonglai; Zhou, Zunning; Yang, Li

2015-02-16

Nitrogen-rich energetic salts involving various cations (lithium, 1; ammonium, 2; hydrazinium, 3; hydroxylammonium, 4; guanidinium, 5; aminoguanidinium, 6; diaminoguanidinium, 7; and triaminoguanidinium, 8) based on nitrogen-rich anion [Zn(BTA)2(H2O)](2-) (N% = 65.37, BTA = N,N-bis[1H-tetrazol-5-yl]amine anion) were synthesized with a simple method. The crystal structures of all compounds except 1, 2, and 6 were determined by single-crystal X-ray diffraction and fully characterized by elemental analysis and FT-IR spectroscopy. The thermal stabilities were investigated by differential scanning calorimetry (DSC). The DSC results show that all compounds exhibit high thermal stabilities (decomposition temperature >200 °C). Additionally, the heats of formation were calculated on the basis of the experimental constant-volume energies of combustion measured by using bomb calorimetry. Lastly, the sensitivities toward impact and friction were assessed according to Bundesamt für Materialforschung (BAM) standard methods.

Synthesis and potential cytotoxic activity of some new benzoxazoles, imidazoles, benzimidazoles and tetrazoles.

PubMed

Arulmurugan, Subramaniyan; Kavitha, Helen P

2013-06-01

2 The present work deals with the synthesis of some novel heterocyclic compounds such as benzoxazoles , 7, 13 and 19, imidazoles 3, 8, 14 and 20, benzimidazoles 4, 9, 15 and 21, and tetrazoles 10, 16, and 22. The synthesized compounds were characterized by IR, 1H NMR, mass spectrometry and elemental analysis. The compounds were evaluated for cytotoxicity against human cancer cell lines such as MCF-7 (breast cancer) and HT-29 (colon cancer) by the MTT assay method. Among the tested compounds, 4,4'-sulfonylbis(N-(2-(1H-benzo[d]imidazol- -2-yl)ethyl)aniline (9), N-bis(2-(benzo[d]oxazol-2-yl)-ethyl)- 6-phenyl-1,3,5-triazine-2,4-diamine (13), N-bis(2-(1H-benzo[ d]imidazol-2-yl)ethyl)-6-phenyl-1,3,5-triazine-2,4-diamine (15) and N-tris(2-1H-benzo[d]imidazol-2-yl)ethyl)- 1,3,5-triazine-2,4,6-triamine (21) showed potent cytotoxicity.

Coordination preference and magnetic properties of FeII assemblies with a bis-azole bearing 1,2,4-triazole and tetrazole

NASA Astrophysics Data System (ADS)

Naik, Anil D.; Railliet, Antoine P.; Dîrtu, Marinela M.; Garcia, Yann

2012-03-01

With a new bis-azole molecular fragment ( Htt) bearing 1,2,4-triazole and tetrazole, a mononuclear complex [Fe(tt)2(H2O)4]·2H2O ( 1), a trinuclear complex [Fe3(tt)6(H2O)6]·2H2O ( 2) and a 1D coordination polymer [Fe(tt)(Htt)2]BF4·2CH3OH ( 3) were obtained by varying reaction conditions. Htt acts either as an anionic or neutral ligand depending upon the reaction medium and pH. Thermal variation of spin states of 1- 3 were investigated in the range 77-300 K by 57Fe Mössbauer spectroscopy. 1 totally remains in high-spin state over the entire temperature range whereas no spin crossover was evidenced in 2. Nearly 1:1 high-spin and low-spin population ratio is found in 3, which remains constant over the entire temperature range investigated.

Mechanism of improved maintenance of 2,3-diphosphoglycerate in stored blood by the xanthone compound 2-(2-hydroxyethoxy)-6-(1-H-tetrazole-5-yl)xanthen-9-one (BW A440C).

PubMed

Beutler, E; Forman, L; West, C; Gelbart, T

1988-03-15

The effect of the xanthone derivative 2-(2-hydroxyethoxy)-6-(1-H-tetrazole-5-yl)xanthen-9-one (BW A440C) on red cells was studied. When added to stored red cells at a concentration of 6 mM, greatly improved preservation of 2,3-diphosphoglycerate (2,3-DPG) was observed. There was no effect on internal pH of the erythrocyte. At a concentration 0.500 mM, many red cell enzyme activities were inhibited completely. At a 0.500 mM concentration, however, inhibition of pyruvate kinase and diphosphoglycerate phosphatase was most striking. Inhibition of either of these enzymes could result in elevation of 2,3-DPG levels. BW A440C in concentrations which elevated 2,3-DPG levels in humans caused a decrease in 2,3-DPG levels in rabbits and markedly impaired the viability of 21-day stored rabbit erythrocytes.

Highly efficient regioselective synthesis, spectroscopic characterizations and DFT calculations of novel hydroxymethylated 1,4-disubstituted-1,2,3-triazole-based sulfonamides

NASA Astrophysics Data System (ADS)

Taheri, Elmira; Mirjafary, Zohreh; Saeidian, Hamid

2018-04-01

The novel hydroxymethylated 1,4-disubstituted-1,2,3-triazole-based sulfonamides were synthesized in excellent yields and high regioselectivity via a one-pot, two-step, three-component reaction of N-propargylsulfonamides, sodium azide, and epoxide derivatives under green conditions. Green and mild reaction condition, commercially readily available and inexpensive starting materials, wide scope and easy work-up are the key features of the present method. The Li+ and Na+ ion affinities of the model structure have been also investigated by density functional theory (DFT) studies to find the applicability of these products as ligand in coordination chemistry.

A convenient synthesis of 1,1-disubstituted 1,2,3,4-tetrahydroisoquinolines via Pictet-Spengler reaction using titanium(IV) isopropoxide and acetic-formic anhydride.

PubMed

Horiguchi, Yoshie; Kodama, Hirokazu; Nakamura, Masayoshi; Yoshimura, Tsuyoshi; Hanezi, Kaori; Hamada, Hiroko; Saitoh, Toshiaki; Sano, Takehiro

2002-02-01

A synthesis of 1,1-disubstituted 1,2,3,4-tetrahydroisoquinolines (6) was achieved in a highly efficient manner via Pictet-Spengler reaction of arylethylamines (1) and acyclic and cyclic ketones (2) using titanium (IV) isopropoxide and acetic-formic anhydride. The cyclization of the in situ formed acyliminium ion (4) to N-formyl 1,2,3,4-tetrahydroisoquinoline (5) was greatly facilitated by using trifluoroacetic acid as an additional reagent. The Pictet-Spengler reaction was carried out by one pot procedure, providing a convenient and effective method for preparing various 1,2,3,4-tetrahydroisoquinolines.

A versatile and convenient protocol for the stereocontrolled synthesis of olefinic insect pheromones.

PubMed

Vasil'ev, A A; Vlasyuk, A L; Gamalevich, G D; Serebryakov, E P

1996-03-01

A combination of the Horner-Emmons synthesis of alkyl 2,4-dienoates with their hydrogenation over complex L.Cr(CO)3 catalysts (L = 3CO or arene) provides a versatile, stereocontrolled and operationally simple approach to the (Z)-disubstituted, (Z)-trisubstituted, (E)-trisubstituted alkenes and skipped (Z,Z)-disubstituted diolefins with a homoallylic type of functionally. This protocol, sometimes supplemented by an enzymatic hydrolysis, was successfully applied to the synthesis of configurationally pure (gp > or = 98%) pheromones of the furniture carpet beetle, dry bean beetle, rusty grain beetle, square-necked grain beetle and a trail-following pheromone mimic for subterranean termites.

Tribological Properties of a Pennzane(Registered Trademark)-Based Liquid Lubricant (Disubstituted Alkylated Cyclopentane) for Low Temperature Space Applications

NASA Technical Reports Server (NTRS)

Venier, Clifford; Casserly, Edward W.; Jones, William R., Jr.; Marchetti, Mario; Jansen, Mark J.; Predmore, Roamer E.

2002-01-01

The tribological properties of a disubstituted alkylated cyclopentane, Pennzane (registered) Synthesized Hydrocarbon Fluid X-1000, are presented. This compound is a lower molecular weight version of the commonly used multiply alkylated cyclopentane, Pennzane X-2000, currently used in many space mechanisms. New, lower temperature applications will require liquid lubricants with lower viscosities and pour points and acceptable vapor pressures. Properties reported include: friction and wear studies and lubricated lifetime in vacuum; additionally, typical physical properties (i.e., viscosity-temperature, pour point, flash and fire point, specific gravity, refractive index, thermal properties, volatility and vapor pressure) are reported.

Synthesis and stereospecificity of 4,5-disubstituted oxazolidinone ligands binding to T-box riboswitch RNA.

PubMed

Orac, Crina M; Zhou, Shu; Means, John A; Boehm, David; Bergmeier, Stephen C; Hines, Jennifer V

2011-10-13

The enantiomers and the cis isomers of two previously studied 4,5-disubstituted oxazolidinones have been synthesized, and their binding to the T-box riboswitch antiterminator model RNA has been investigated in detail. Characterization of ligand affinities and binding site localization indicates that there is little stereospecific discrimination for binding antiterminator RNA alone. This binding similarity between enantiomers is likely due to surface binding, which accommodates ligand conformations that result in comparable ligand-antiterminator contacts. These results have significant implications for T-box antiterminator-targeted drug discovery and, in general, for targeting other medicinally relevant RNA that do not present deep binding pockets.

Synthesis and stereospecificity of 4,5-disubstituted oxazolidinone ligands binding to T-box riboswitch RNA

PubMed Central

Orac, Crina M.; Zhou, Shu; Means, John A.; Boehm, David; Bergmeier, Stephen C.; Hines, Jennifer V.

2012-01-01

The enantiomers and the cis isomers of two previously studied 4,5-disubstituted oxazolidinones have been synthesized and their binding to the T-box riboswitch antiterminator model RNA investigated in detail. Characterization of ligand affinities and binding site localization indicate that there is little stereospecific discrimination for binding antiterminator RNA alone. This binding similarity between enantiomers is likely due to surface binding, which accommodates ligand conformations that result in comparable ligand-antiterminator contacts. These results have significant implications for T-box antiterminator-targeted drug discovery and, in general, for targeting other medicinally relevant RNA that do not present deep binding pockets. PMID:21812425

Synthesis and Evaluation of In Vitro Antibacterial and Antitumor Activities of Novel N,N-Disubstituted Schiff Bases

PubMed Central

Luo, Heng; Xia, Yu-fen; Sun, Bao-fei; Huang, Li-rong; Wang, Xing-hui; Lou, Hua-yong; Zhu, Xu-hui

2017-01-01

To get inside the properties of N,N-disubstituted Schiff bases, we synthesized three high-yielding benzaldehyde Schiff bases. We used the reaction between salicylaldehyde and different diamine compounds, including diamine, ethanediamine, and o-phenylenediamine, determining the structure of obtained molecules by nuclear magnetic resonance spectroscopy and electrospray ionization mass spectroscopy. We thus evaluated the microbicidal and antitumor activity of these compounds, showing that salicylaldehyde-hydrazine hydrate Schiff base (compound 1a) significantly inhibited the growth of S. aureus; salicylaldehyde-o-phenylenediamine Schiff base (compound 1c) displayed a strong capability to inhibit the proliferation of leukemia cell lines K562 and HEL. Moreover, we observed that the antibacterial action of 1a might be associated with the regulation of the expression of key virulence genes in S. aureus. Compound 1c resulted in a strong apoptotic activity against leukemia cells, also affecting the cell cycle distribution. Overall, our novel N,N-disubstituted Schiff bases possess unique antibacterial or antitumor activities that exhibit the potent application prospect in prophylactic or therapeutic interventions, providing new insights for developing new antibacterial and anticancer chemical agents. PMID:28713593

Fluorogenic Strain-Promoted Alkyne-Diazo Cycloadditions

PubMed Central

Friscourt, Frédéric; Fahrni, Christoph J.; Boons, Geert-Jan

2016-01-01

Fluorogenic reactions in which non- or weakly-fluorescent reagents produce highly fluorescent products are attractive for detecting a broad range of compounds in the fields of bio-conjugation and material sciences. We report here that Fl-DIBO, a dibenzocyclooctyne derivative modified with a cyclopropenone moiety, can undergo fast strain-promoted cycloadditions under catalyst-free conditions with azides, nitrones, nitrile oxides as well as mono- and disubstituted diazo-derivatives. While the reaction with nitrile oxides, nitrones and disubstituted diazo compounds gave cycloadducts with low quantum yield, monosubstituted diazo reagents produced 1H-pyrazole derivatives that exhibited a ~160-fold fluorescence enhancement over Fl-DIBO combined with a greater than 10,000-fold increase in brightness. Concluding from quantum chemical calculations, fluorescence quenching of 3H-pyrazoles, which are formed by reaction with disubstituted diazo-derivatives, is likely due to the presence of energetically low-lying (n,π*) states. The fluorogenic probe Fl-DIBO was successfully employed for the labeling of diazo-tagged proteins without detectable background signal. Diazo-derivatives are emerging as attractive reporters for the labeling of biomolecules and the studies presented here demonstrate that Fl-DIBO can be employed for visualizing such biomolecules without the need for probe washout. PMID:26330090

Classical Example of Total Kinetic and Thermodynamic Control: The Diels-Alder Reaction between DMAD and Bis-furyl Dienes.

PubMed

Borisova, Kseniya K; Kvyatkovskaya, Elizaveta A; Nikitina, Eugeniya V; Aysin, Rinat R; Novikov, Roman A; Zubkov, Fedor I

2018-04-20

A rare example of chemospecificity in the tandem Diels-Alder reaction of activated alkynes and bis-dienes has been revealed. The reaction between bis-furyl dienes and DMAD occurs at 25-80 °C and leads to kinetically controlled "pincer" adducts, 4a,8a-disubstituted 1,4:5,8-diepoxynaphthalenes. On the contrary, only thermodynamically controlled "domino" adducts (2,3-disubstituted 1,4:5,8-diepoxynaphthalenes) are formed in the same reaction at 140 °C. The "pincer" adducts can be transformed to the "domino" adducts at heating. The rate constants for reactions of both types were calculated using dynamic 1 H NMR spectroscopy.

Design, synthesis and biological evaluation of di-substituted cinnamic hydroxamic acids bearing urea/thiourea unit as potent histone deacetylase inhibitors.

PubMed

Ning, Chengqing; Bi, Yanjing; He, Yujun; Huang, WenYuan; Liu, Lifei; Li, Yi; Zhang, Sihan; Liu, Xiaoyu; Yu, Niefang

2013-12-01

A novel class of di-substituted cinnamic hydroxamic acid derivatives containing urea or thiourea unit was designed, synthesized and evaluated as HDAC inhibitors. All tested compounds demonstrated significant HDAC inhibitory activities and anti-proliferative effects against diverse human tumor cell lines. Among them, 7l exhibited most potent pan-HDAC inhibitory activity, with an IC50 value of 130 nM. It also showed strong cellular inhibition against diverse cell lines including HCT-116, MCF-7, MDB-MB-435 and NCI-460, with GI50 values of 0.35, 0.22, 0.51 and 0.48 μM, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

Synthesis and anthelmintic activity of 2,2'-disubstituted 5,5'-dibenzimidazolylsulfides and sulfones.

PubMed

Abuzar, S; Sharma, S; Visen, P K; Gupta, S; Katiyar, J C

1986-03-01

A number of substituted diphenylsulfides and sulfones (4-11) and 2,2'-disubstituted-5,5'-dibenzimidazolyl sulfides and sulphones (12-19) have been synthesized starting from 5-chloro-2-nitroacetanilide and (3) 4,4'-dichlorodiphenyl sulfone (9), respectively. Among the compounds tested against Ancylostoma ceylanicum in hamsters and Hymenolepis nana in rats and mice, 14, 15, 18 and 19 removed 100% of the worms at an oral dose of 25 mg/kg X 1 to 250 mg/kg X 3. Some of the compounds were tested for their blood schizontocidal activity against Plasmodium berghei in mice but none showed any activity up to an oral dose of 10 mg/kg given for 6 days.

Fluorogenic Strain-Promoted Alkyne-Diazo Cycloadditions.

PubMed

Friscourt, Frédéric; Fahrni, Christoph J; Boons, Geert-Jan

2015-09-28

Fluorogenic reactions, in which non- or weakly fluorescent reagents produce highly fluorescent products, are attractive for detecting a broad range of compounds in the fields of bioconjugation and material sciences. Herein, we report that a dibenzocyclooctyne derivative modified with a cyclopropenone moiety (Fl-DIBO) can undergo fast strain-promoted cycloaddition reactions under catalyst-free conditions with azides, nitrones, nitrile oxides, as well as mono- and disubstituted diazo-derivatives. Although the reaction with nitrile oxides, nitrones, and disubstituted diazo compounds gave cycloadducts with low quantum yield, monosubstituted diazo reagents produced 1H-pyrazole derivatives that exhibited an approximately 160-fold fluorescence enhancement over Fl-DIBO combined with a greater than 10,000-fold increase in brightness. Concluding from quantum chemical calculations, fluorescence quenching of 3H-pyrazoles, which are formed by reaction with disubstituted diazo-derivatives, is likely due to the presence of energetically low-lying (n,π*) states. The fluorogenic probe Fl-DIBO was successfully employed for the labeling of diazo-tagged proteins without detectable background signal. Diazo-derivatives are emerging as attractive reporters for the labeling of biomolecules, and the studies presented herein demonstrate that Fl-DIBO can be employed for visualizing such biomolecules without the need for probe washout. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

One-Pot Catalytic Enantio- and Diastereoselective Syntheses of anti-, syn-cis-Disubstituted, and syn-Vinyl Cyclopropyl Alcohols

PubMed Central

Kim, Hun Young; Salvi, Luca; Carroll, Patrick J.; Walsh, Patrick J.

2009-01-01

Highly enantio- and diastereoselective methods for the synthesis of a variety of cyclopropyl alcohols are reported. These methods represent the first one-pot approaches to syn-vinyl cyclopropyl alcohols, syn-cis-disubstituted cyclopropyl alcohols, and anti-cyclopropyl alcohols from achiral precursors. The methods begin with enantioselective C–C bond formations promoted by a MIB-based zinc catalyst to generate allylic alkoxide intermediates. The intermediates are then subjected to in situ alkoxide-directed cyclopropanation to provide cyclopropyl alcohols. In the synthesis of vinyl cyclopropyl alcohols, hydroboration of enynes is followed by transmetalation of the resulting dienylborane to zinc to provide dienylzinc reagents. Enantioselective addition to aldehydes generates the requisite dienyl zinc alkoxides, which are then subjected to in situ cyclopropanation to furnish vinyl cyclopropyl alcohols. Cyclopropanation occurs at the double bond allylic to the alkoxide. Using this method, syn-vinylcyclopropyl alcohols are obtained in 65–85% yield, 76–93% ee, and >19:1 dr. To prepare anti-cyclopropanols, enantioselective addition of alkylzinc reagents to conjugated enals provides allylic zinc alkoxides. Because direct cyclopropanation provides syn-cyclopropyl alcohols, the intermediate allylic alkoxides were treated with TMSCl/Et3N to generate intermediate silyl ethers. In situ cyclopropanation of the allylic silyl ether resulted in cyclopropanation to form the anti-cyclopropyl silyl ether. Workup with TBAF affords the anti-cyclopropyl alcohols in one-pot in 60–82% yield, 89–99% ee, and ≥10:1 dr. For the synthesis of cis-disubstituted cyclopropyl alcohols, in situ generated (Z)-vinyl zinc reagents were employed in asymmetric addition to aldehydes to generate (Z)-allylic zinc alkoxides. In situ cyclopropanation provides syn-cis-disubstituted cyclopropyl alcohols in 42–70% yield, 88–97% ee, and >19:1 dr. These one-pot procedures enable the synthesis of a diverse array of cyclopropyl alcohol building blocks with high enantio- and diastereoselectivities. PMID:19954146

Polyethylene Glycol-Poly(2-Methyl-5-Vinyl Tetrazole) Polymer Blend (A desensitizing Binder for Propellants and Explosives)

DTIC Science & Technology

1989-03-01

PVA, CTBN , PBAA, PMMA, etc. As a test of this predictability, we dissolved a vinyl acetate polymer in THF, and then added PMVT, and did succeed in...Polyvinyl acetate CTBN Carboxy terminated butadiene acrylonitrile PBAA Polybutadiene acrylic acid PMMA Polymethyl. methacrylate THF Tetrahydrofuran NMR

Search for Compounds with Hypoglycemic Activity in the Series of 1-[2-(1H-Tetrazol-5-yl)-R1-phenyl]-3-R2-phenyl(ethyl)ureas and R1-Tetrazolo[1,5-c]quinazolin-5(6H)-ones

PubMed Central

Antypenko, Oleksii M.; Kovalenko, Sergiy I.; Zhernova, Galina O.

2016-01-01

Methods of 1-[2-(1H-tetrazol-5-yl)-R1-phenyl]-3-R2-phenyl(ethyl)ureas and R1-tetrazolo[1,5-c]quinazolin-5(6H)-ones synthesis were designed. IR, LC-MS, 1H NMR, and elemental analysis data evaluated the structure and purity of the obtained compounds. Different products, depending on the reaction conditions, were distinguished and discussed. The preliminary hypoglycemic activity of 36 synthesized compounds was revealed. Docking studies to 11β-hydroxysteroid dehydrogenase 1, γ-peroxisome proliferator-activated receptor, and dipeptidyl peptidase-4 were conducted. Eight of these substances were further tested on glucocorticoid-induced insulin resistance models, namely glucose tolerance, oral rapid insulin, and adrenalin tests. One of the most active compounds turned out to be tetrazolo[1,5-c]quinazolin-5(6H)-one 3.1, exceeding the reference drugs Metformin (50 and 200 mg/kg) and Gliclazide (50 mg/kg). PMID:27222601

Crystal structures of the three closely related compounds: bis-[(1H-tetra-zol-5-yl)meth-yl]nitramide, tri-amino-guanidinium 5-({[(1H-tetra-zol-5-yl)meth-yl](nitro)-amino}-meth-yl)tetra-zol-1-ide, and di-ammonium bis-[(tetra-zol-1-id-5-yl)meth-yl]nitramide monohydrate.

PubMed

Mitchell, Lauren A; Imler, Gregory H; Parrish, Damon A; Deschamps, Jeffrey R; Leonard, Philip W; Chavez, David E

2017-07-01

In the mol-ecule of neutral bis-[(1 H -tetra-zol-5-yl)meth-yl]nitramide, (I), C 4 H 6 N 10 O 2 , there are two intra-molecular N-H⋯O hydrogen bonds. In the crystal, N-H⋯N hydrogen bonds link mol-ecules, forming a two-dimensional network parallel to (-201) and weak C-H⋯O, C-H⋯N hydrogen bonds, and inter-molecular π-π stacking completes the three-dimensional network. The anion in the molecular salt, tri-amino-guanidinium 5-({[(1 H -tetra-zol-5-yl)meth-yl](nitro)-amino}-meth-yl)tetra-zol-1-ide, (II), CH 9 N 6 + ·C 4 H 5 N 10 O 2 - , displays intra-molecular π-π stacking and in the crystal, N-H⋯N and N-H⋯O hydrogen bonds link the components of the structure, forming a three-dimensional network. In the crystal of di-ammonium bis-[(tetra-zol-1-id-5-yl)meth-yl]nitramide monohydrate, (III), 2NH 4 + ·C 4 H 4 N 10 O 2 2- ·H 2 O, O-H⋯N, N-H⋯N, and N-H⋯O hydrogen bonds link the components of the structure into a three-dimensional network. In addition, there is inter-molecular π-π stacking. In all three structures, the central N atom of the nitramide is mainly sp 2 -hybridized. Bond lengths indicate delocalization of charges on the tetra-zole rings for all three compounds. Compound (II) was found to be a non-merohedral twin and was solved and refined in the major component.

Synthesis and binding affinity of new 1,4-disubstituted triazoles as potential dopamine D(3) receptor ligands.

PubMed

Insua, Ignacio; Alvarado, Mario; Masaguer, Christian F; Iglesias, Alba; Brea, José; Loza, María I; Carro, Laura

2013-10-15

A series of new 1,4-disubstituted triazoles was prepared from appropriate arylacetylenes and aminoalkylazides using click chemistry methodology. These compounds were evaluated as potential ligands on several subtypes of dopamine receptors in in vitro competition assays, showing high affinity for dopamine D3 receptors, lower affinity for D2 and D4, and no affinity for the D1 receptors. Compound 18 displayed the highest affinity at the D3 receptor with a Ki value of 2.7 nM, selectivity over D2 (70-fold) and D4 (200-fold), and behaviour as a competitive antagonist in the low nanomolar range. Copyright © 2013 Elsevier Ltd. All rights reserved.

Enantiodivergent Synthesis of (+)- and (-)-Pyrrolidine 197B: Synthesis of trans-2,5-Disubstituted Pyrrolidines by Intramolecular Hydroamination.

PubMed

Pérez, Sixto J; Purino, Martín A; Cruz, Daniel A; López-Soria, Juan M; Carballo, Rubén M; Ramírez, Miguel A; Fernández, Israel; Martín, Víctor S; Padrón, Juan I

2016-10-17

A highly efficient, diastereoselective, iron(III)-catalyzed intramolecular hydroamination/cyclization reaction involving α-substituted amino alkenes is described. Thus, enantiopure trans-2,5-disubstituted pyrrolidines and trans-5-substituted proline derivatives were synthesized by means of a combination of enantiopure starting materials, easily available from l-α-amino acids, with sustainable metal catalysts such as iron(III) salts. The scope of this methodology is highlighted in an enantiodivergent approach to the synthesis of both (+)- and (-)-pyrrolidine 197B alkaloids from l-glutamic acid. In addition, a computational study was carried out to gain insight into the complete diastereoselectivity of the transformation. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of new 2,5-disubstituted-1,3,4-thiadiazole derivatives and their in vivo anticonvulsant activity.

PubMed

Harish, K P; Mohana, K N; Mallesha, L

2014-01-01

A series of 2,5-disubstituted-1,3,4-thiadiazole derivatives were synthesized by the reaction of 3-(2-cyanopropan-2-yl)-N-(5-(piperazine-1-yl)-1,3,4-thiadiazol-2-yl)benzamide with various sulfonyl chlorides and evaluated for their anticonvulsant activity in MES test. Rotorod method was employed to determine the neurotoxicity. The purity of the compounds is confirmed on the basis of their elemental analysis. The structures of all the new compounds are established on the basis of 1H NMR and mass spectral data. Out of fifteen compounds, three were found to be potent anticolvunstants. The same compounds showed no neurotoxicity at the maximum dose administered (100 mg/kg).

Synthesis and antileishmanial activity of 6-mono-substituted and 3,6-di-substituted acridines obtained by acylation of proflavine.

PubMed

Di Giorgio, Carole; Shimi, Kamal; Boyer, Gérard; Delmas, Florence; Galy, Jean-Pierre

2007-10-01

Two new series of diaminoacridinic derivatives obtained from proflavine and N-(6-amino-3-acridinyl)acetamide were synthesised and assessed for their cytotoxic and antileishmanial activities. Two compounds, N-[6-(acetylamino)-3-acridinyl]acetamide and N-[6-(benzoylamino)-3-acridinyl]benzamide demonstrated highly specific antileishmanial properties against the intracellular amastigote form of the parasite. Structure-activity relationships established that the antiproliferative activity against human cells was greatly enhanced by the presence of a benzoylamino group in 6-mono-substituted acridines, while the presence of two acetylamino or benzoylamino groups in 3,6-di-substituted acridines strongly increased the specificity of the molecules for Leishmania parasite, suggesting that symmetric conformations could preferentially interfere with Leishmania metabolism.

Atropisomerisation in sterically hindered α,β-disubstituted cyclopentenones derived from an intermolecular cobalt(0)-mediated Pauson-Khand reaction.

PubMed

Moulton, Benjamin E; Lynam, Jason M; Duhme-Klair, Anne-Kathrin; Zheng, Wenxu; Lin, Zhenyang; Fairlamb, Ian J S

2010-12-07

4-(2-Phenylethynyl)-2H-chromen-2-one reacts with norbornene and Co(2)(CO)(8) in an intermolecular Pauson-Khand reaction by focused microwave dielectric heating. Two regioisomeric products are formed; the electron-deficient coumarin moiety preferentially occupies the β-position of the cyclopentenone ring system, whereas the phenyl occupies the α-position. The sterically hindered α,β-(2,3)-disubstituted cyclopentenone regioisomeric products exhibit pronounced atropisomerisation, and the magnitude of the energetic barrier to interconversion between these atropisomers is dependent on the relative position of the coumarin moieties. Interconversion is slow when the coumarin is found in the α-position, whereas interconversion is relatively fast when found in the β-position.

Synthesis and antimicrobial evaluation of ester-linked 1,4-disubstituted 1,2,3-triazoles with a furyl/thienyl moiety.

PubMed

Kaushik, C P; Luxmi, Raj; Singh, Dharmendra; Kumar, Ashwani

2017-02-01

Twenty ester-linked 1,4-disubstituted 1,2,3-triazoles having a furyl/thienyl moiety have been synthesized from heteroaryl prop-2-yn-1-yl carboxylate and aromatic azides via a Cu(I) catalyzed 1,3-dipolar cycloaddition. All the synthesized compounds were characterized by FTIR, [Formula: see text]H NMR, [Formula: see text]C NMR spectroscopy and HRMS. Synthesized triazoles were tested in vitro for antimicrobial evaluation against Gram-negative bacteria-Escherichia coli, Enterobacter aerogenes and Klebsiella pneumoniae; Gram-positive bacteria-Staphylococcus aureus and two fungal strains-Candida albicans and Aspergillus niger, reflecting moderate to good activity. The structure of compound 6f was also confirmed by X-ray crystallography (CCDC 1469326).

Rational synthesis of an exceptionally stable Zn(II) metal-organic framework for the highly selective and sensitive detection of picric acid.

PubMed

Hu, Yingli; Ding, Meili; Liu, Xiao-Qin; Sun, Lin-Bing; Jiang, Hai-Long

2016-04-28

Based on an organic ligand involving both carboxylate and tetrazole groups, a chemically stable Zn(II) metal-organic framework has been rationally synthesized and behaves as a fluorescence chemosensor for the highly selective and sensitive detection of picric acid, an extremely hazardous and strong explosive.

Is there substituent cross-interaction effect in all the conjugated systems containing Cdbnd N polar bond? The substituent effects on the NMR chemical shifts of 2,5-disubstituted pyrimidines

NASA Astrophysics Data System (ADS)

Yuan, Hua; Zhang, Yan; Chen, Chun-Ni; Li, Meng-Yang

2018-03-01

The substituent cross-interaction effect in the substituted benzylidene anilines (p-Xsbnd C6H4sbnd CHdbnd Nsbnd C6H4sbnd Y-p) has been observed and widely investigated. In order to investigate whether the substituent cross-interaction effect exist in all the conjugated systems containing Cdbnd N polar bond, this paper employed 2-X-5-Y pyrimidines as the model compounds for study. The influences of substituents X and Y on the 1H NMR and 13C NMR chemical shifts of 2, 5-disubsitituted pyrimidines have been systematically investigated. Quantitative structure-chemical shifts relationship models have been built for δ(H4,6), δ(C2), δ(C4,6) and δ(C5) with four to six molecular descriptors. These models were confirmed of good stability and predictive performances by leave-one-out cross validation. This study indicates that the substituent effects of 2,5-disubstituted pyrimidines are much more complex than that of the substituted benzylidene anilines. More structural factors besides of Hammett parameter should be taken into consideration. Different from the substituted benzylidene anilines, the cross-interaction effect (Δσ2) of substituents X and Y has little contribution to δ(H4,6), δ(C2), δ(C5) and δ(C4,6) of 2,5-disubstituted pyrimidines.

Synthesis, characterization and spectroscopic behavior of novel 2-oxo-1,4-disubstituted-1,2,5,6-tetrahydrobenzo[h]quinoline-3-carbonitrile dyes.

PubMed

Khan, Salman A; Asiri, Abdullah M; Al-Thaqafy, Saad H; Faidallah, Hassan M; El-Daly, Samy A

2014-12-10

Two synthetic pathways were adopted to synthesize the target 2-oxo-1,4-disubstituted-1,2,5,6-tetrahydro-benzo[h]quinoline-3-carbonitriles. Structure of the synthesized compounds has been characterized based on FT-IR, (1)H NMR, (13)C NMR and elemental analyses. UV-Vis and fluorescence spectroscopy measurements provided that all compounds are good absorbent and fluorescent. Fluorescence polarity study demonstrated that these compounds were sensitive to the polarity of the microenvironment provided by different solvents. In addition, spectroscopic and physicochemical parameters, including singlet absorption, extinction coefficient, Stokes shift, oscillator strength and dipole moment were investigated in order to explore the analytical potential of synthesized compounds. Copyright © 2014 Elsevier B.V. All rights reserved.

Near-infrared spectroscopic studies of the hydrogen bonding between thioacetamide and N, N-disubstituted benzamide derivatives in CCl 4

NASA Astrophysics Data System (ADS)

Choi, Young Sang; Kim, Jeongkwon; Park, Jeunghee; Yu, Jeong-A.; Yoon, Chang-Ju

1996-11-01

The hydrogen bonding interactions between thioacetamide (TA) and several N, N-disubstituted benzamides ( N, N-dimethylbenzamide (DMBA), N-methoxy- N-methylbenzamide (MMBA), N, N-diethyl- m-toluamide (DEMT), and N, N-diethyl-2,5-difluorobenzamide (DEDF)) have been studied using near-infrared absorption spectroscopy. Thermodynamic parameters for the interactions between TA and benzamides were determined by analyzing the νN-Has + amide II combination band of TA. The - ΔH0 values, indicating the intrinsic strength of hydrogen bonding, are -17.4, -21.6, -21.9 and -20.8 kJ mol -1 for DMBA, MMBA, DEMT and DEDF, respectively. The results show that the inductive and resonance effects of substituents appear to influence the formation of hydrogen bonds.

Isocyanides Derived from α,α-Disubstituted Amino Acids: Synthesis and Antifouling Activity Assessment.

PubMed

Inoue, Yuki; Takashima, Shuhei; Nogata, Yasuyuki; Yoshimura, Erina; Chiba, Kazuhiro; Kitano, Yoshikazu

2018-03-01

Herein, we contribute to the development of environmentally friendly antifoulants by synthesizing eighteen isocyanides derived from α,α-disubstituted amino acids and evaluating their antifouling activity/toxicity against the cypris larvae of the Balanus amphitrite barnacle. Almost all isocyanides showed good antifouling activity without significant toxicity and exhibited EC 50 values of 0.07 - 7.30 μg/mL after 120-h exposure. The lowest EC 50 values were observed for valine-, methionine-, and phenylalanine-derived isocyanides, which achieved > 95% cypris larvae settlement inhibition at concentrations of less than 30 μg/mL without exhibiting significant toxicity. Thus, the prepared isocyanides should be useful for further research focused on the development of environmentally friendly antifouling agents. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

Molecular docking guided structure based design of symmetrical N,N'-disubstituted urea/thiourea as HIV-1 gp120-CD4 binding inhibitors.

PubMed

Sivan, Sree Kanth; Vangala, Radhika; Manga, Vijjulatha

2013-08-01

Induced fit molecular docking studies were performed on BMS-806 derivatives reported as small molecule inhibitors of HIV-1 gp120-CD4 binding. Comprehensive study of protein-ligand interactions guided in identification and design of novel symmetrical N,N'-disubstituted urea and thiourea as HIV-1 gp120-CD4 binding inhibitors. These molecules were synthesized in aqueous medium using microwave irradiation. Synthesized molecules were screened for their inhibitory ability by HIV-1 gp120-CD4 capture enzyme-linked immunosorbent assay (ELISA). Designed compounds were found to inhibit HIV-1 gp120-CD4 binding in micromolar (0.013-0.247 μM) concentrations. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Pauson-Khand Reaction as a New Entry to the Synthesis of Bridged Bicyclic Heterocycles: Application to the Enantioselective Total Synthesis of (−)-Alstonerine

PubMed Central

Miller, Kenneth A.; Shanahan, Charles S.; Martin, Stephen F.

2008-01-01

The first application of the Pauson-Khand reaction (PKR) to the synthesis of azabridged bicyclic structures is described. Compounds containing azabicyclo[3.3.1]nonane and azabicyclo[3.2.1]octane rings fused to cyclopentenones were efficiently constructed via the PKR of cis-2,6-disubstituted N-acyl piperidine enyne substrates, many of which can be readily prepared from 4-methoxypyridine in a few steps. Moreover, the PKR of cis-2,6-disubstituted piperazine enynes allowed the preparation of diazabicyclo[3.3.1]nonanes fused to cyclopentenones. This new strategy for the synthesis of azabridged bicyclic frameworks was exploited as a key step in a concise, enantioselective total synthesis of the macroline alklaoid (−)-alstonerine. PMID:19122869

The Pauson-Khand Reaction as a New Entry to the Synthesis of Bridged Bicyclic Heterocycles: Application to the Enantioselective Total Synthesis of (-)-Alstonerine.

PubMed

Miller, Kenneth A; Shanahan, Charles S; Martin, Stephen F

2008-01-01

The first application of the Pauson-Khand reaction (PKR) to the synthesis of azabridged bicyclic structures is described. Compounds containing azabicyclo[3.3.1]nonane and azabicyclo[3.2.1]octane rings fused to cyclopentenones were efficiently constructed via the PKR of cis-2,6-disubstituted N-acyl piperidine enyne substrates, many of which can be readily prepared from 4-methoxypyridine in a few steps. Moreover, the PKR of cis-2,6-disubstituted piperazine enynes allowed the preparation of diazabicyclo[3.3.1]nonanes fused to cyclopentenones. This new strategy for the synthesis of azabridged bicyclic frameworks was exploited as a key step in a concise, enantioselective total synthesis of the macroline alklaoid (-)-alstonerine.

Synthesis of Cis, syndiotactic A -alt-B Copolymers from Two Enantiomerically Pure Trans -2,3-Disubstituted-5,6-Norbornenes

DOE PAGES

Jang, Eun Sil; John, Jeremy M.; Schrock, Richard R.

2016-09-06

Cis,syndiotactic A-alt-B copolymers, where A and B are two enantiomerically pure trans-2,3-disubstituted-5,6-norbornenes with “opposite” chiralities, can be prepared with stereogenic-at-metal initiators of the type M(NR)(CHR')(OR”)(pyrrolide). Formation of a high percentage of alternating AB copolymer linkages relies on an inversion of chirality at the metal with each propagating step and a relatively fast formation of an AB sequence as a consequence of a preferred diastereomeric relationship between the chirality at the metal and the chirality of the monomer. Finally, this approach to formation of an alternating AB copolymer contrasts dramatically with the principle of forming AB copolymers from achiral monomers andmore » catalysts.« less

Highly efficient SO2 capture by dual functionalized ionic liquids through a combination of chemical and physical absorption.

PubMed

Cui, Guokai; Wang, Congmin; Zheng, Junjie; Guo, Yan; Luo, Xiaoyan; Li, Haoran

2012-03-07

Two kinds of dual functionalized ionic liquids with ether-functionalized cations and tetrazolate anions were designed, prepared, and used for SO(2) capture, which exhibit an extremely high SO(2) capacity and excellent reversibility through a combination of chemical and physical absorption. This journal is © The Royal Society of Chemistry 2012

Three coordination polymers constructed from 5-(4-(tetrazol-5-yl)phenyl)isophthalic acid: Synthesis, crystal structure and properties

NASA Astrophysics Data System (ADS)

Zhai, Dandan; Sun, Wujuan; Fan, Fei; Liao, Xuzhao; Chen, Sanping; Yang, Xuwu

2017-04-01

Three new coordination polymers, namely, {[Co2(TPA)(μ3-O)3]·0.5DMA}n (1), {[Co(H2TPA)(bibp)(H2O)3]·H2O}n (2) and {[Cd3(TPA)2(phen)4]·4H2O}n (3), (H3TPA = 5-(4-(tetrazol-5-yl)phenyl)isophthalic acid, bibp = 4,4'-bis(imidazolyl)biphenyl, phen = 1,10-phenanthroline and DMA = N,N-dimethylacetamide), have been synthesized under solvothermal conditions and structurally characterized by elemental analysis, IR spectroscopy, powder X-ray diffraction (PXRD) and single-crystal X-ray diffraction analysis. Polymer 1 exhibits a three-dimensional (3D) structure constructed from 5-connected secondary building units (SBUs) [Co3(μ3-O)] and 3-connected H3TPA ligands. Polymer 2 has a 1D zigzag polymer chain connected by H3TPA and bibp ligands. Polymer 3 features an unusual 3D framework with a (3,4,2)-connected {4; 6;8}{4; 62;83} topology. Moreover, the thermal stabilities of 1-3 and photoluminescence properties of 3 have been investigated. Magnetic susceptibility measurements indicate that polymers 1-2 display antiferromagnetic exchange properties.

Discovery, synthesis and in combo studies of a tetrazole analogue of clofibric acid as a potent hypoglycemic agent.

PubMed

Navarrete-Vázquez, Gabriel; Alaniz-Palacios, Alfredo; Hidalgo-Figueroa, Sergio; González-Acevedo, Cristina; Ávila-Villarreal, Gabriela; Estrada-Soto, Samuel; Webster, Scott P; Medina-Franco, José L; López-Vallejo, Fabian; Guerrero-Álvarez, Jorge; Tlahuext, Hugo

2013-06-01

A tetrazole isosteric analogue of clofibric acid (1) was prepared using a short synthetic route and was characterized by elemental analysis, NMR ((1)H, (13)C) spectroscopy, and single-crystal X-ray diffraction. The in vitro inhibitory activity of 1 against 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) was evaluated, showing a moderate inhibitory enzyme activity (51.17% of inhibition at 10 μM), being more active than clofibrate and clofibric acid. The antidiabetic activity of compound 1 was determined at 50 mg/Kg single dose using a non insulin dependent diabetes mellitus rat model. The results indicated a significant decrease of plasma glucose levels, during the 7h post-administration. Additionally, we performed a molecular docking of 1 into the ligand binding pocket of one subunit of human 11β-HSD1. In this model, compound 1 binds into the catalytic site of 11β-HSD1 in two different orientations. Both of them, show important short contacts with the catalytic residues Ser 170, Tyr 183, Asp 259 and also with the nicotinamide ring of NADP(+). Copyright © 2013 Elsevier Ltd. All rights reserved.

Tautomerism and thermal decomposition of tetrazole: high-level ab initio study.

PubMed

Kiselev, Vitaly G; Cheblakov, Pavel B; Gritsan, Nina P

2011-03-10

The mutual interconversion and decomposition reactions of four tetrazole isomers (1H-TZ, 2H-TZ, 5H-TZ, and an N-heterocyclic carbene 14H) have been studied theoretically using the W1 high-level procedure. Computations allowed resolution of the existing discrepancies in the mechanism and key intermediates of TZ thermolysis. The tautomeric equilibria between 1H-TZ, 2H-TZ, and 14H turned out to play a very important role in the mechanism of thermal decomposition. Although the barriers of monomolecular tautomeric transformations were found to be high (∼50-70 kcal/mol), the concerted double H atom transfer reactions in the H-bonded complexes of TZ tautomers have profoundly lower barriers (∼18-28 kcal/mol). These reactions lead to fast interconversion between 1H-TZ, 2H-TZ, and 14H. The carbene 14H has never been considered before; however, it was predicted to be a key intermediate in the mechanism of thermal decomposition of TZ. For all species considered, the unimolecular reactions of N(2) elimination were predicted to dominate over the elimination of hydrazoic acid. In agreement with existing experimental data, the effective activation energy of thermolysis was calculated to be 36.2 kcal/mol.

Adsorption and photocatalytic properties of transition metal Zinc(II) complex based on 5-(4-(tetrazol-5-yl)phenyl)isophthalic acid

NASA Astrophysics Data System (ADS)

Qiao, Yu; Ren, Shan-Shan; Liu, Li-Hui; Guan, Wei-Sheng; Li, Zhi-Min; Che, Guang-Bo; Liu, Chun-Bo; Wang, Yan-Yan; Wang, Qing-Wei; Li, Xiu-Ying; Zhu, En-Wei

2018-06-01

A new coordination polymeric zinc(II) complex, namely, [Zn2(L)(H2O)3]n·nNO3(1), (H3L = 5-(4-(tetrazol-5-yl)phenyl)isophthalic acid) has been synthesized under solvothermal conditions and structurally characterized by elemental analysis, IR spectroscopy, single-crystal X-ray diffraction analysis and powder X-ray diffraction. Complex 1 exhibits a three-dimensional structure with a Schläfli symbol of 44•69•82 topologies, constructed from two crystallographically independent five and six coordinated mode with metal center and connected H3L ligands. The complex has good thermal stability and excellent photoluminescent property. Furthermore, by comparing the photoluminescent and photocatalytic mutation results induced by interconversion of metal ions, we confirm that the properties mutation induced by metal ions is much controllable and obvious. In addition, the complex exhibits significantly enhanced photocatalytic activity for methylene blue (MB) under UV light irradiation (λ < 400 nm), and the degradation rate could reach 75% in 80 min. Meanwhile trapping experiments indicated that the •O2- and h+ are the main activated species.

Synthesis and dual PPARalpha/delta agonist effects of 1,4-disubstituted 1,2,3-triazole analogues of GW 501516.

PubMed

Ciocoiu, Calin C; Nikolić, Natasa; Nguyen, Huyen Hoa; Thoresen, G Hege; Aasen, Arne J; Hansen, Trond Vidar

2010-07-01

Ten 1,4-disubstituted 1,2,3-triazoles 2a-2j were prepared and tested for their ability to increase oleic acid oxidation in human myotubes using a high-throughput multiwell assay. Compounds 2e (2-{4-[(1-(3-fluoro-4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)methylthio]-2-methylphenoxy}acetic acid) and 2i (2-{4-[(1-(3-chloro-4-(trifluoromethoxy)phenyl)-1H-1,2,3-triazol-4-yl)methylthio]-2-methylphenoxy}acetic acid) exhibited potent agonist activities. Compounds 2e and 2i also exhibited powerful agonist effects for both PPARalpha and PPARdelta in a luciferase-based assay. Consequently, these triazoles can be categorized as dual PPAR agonists. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

A Twist on Facial Selectivity of Hydride Reductions of Cyclic Ketones: Twist-Boat Conformers in Cyclohexanone, Piperidone, and Tropinone Reactions

PubMed Central

2015-01-01

The role of twist-boat conformers of cyclohexanones in hydride reductions was explored. The hydride reductions of a cis-2,6-disubstituted N-acylpiperidone, an N-acyltropinone, and tert-butylcyclohexanone by lithium aluminum hydride and by a bulky borohydride reagent were investigated computationally and compared to experiment. Our results indicate that in certain cases, factors such as substrate conformation, nucleophile bulkiness, and remote steric features can affect stereoselectivity in ways that are difficult to predict by the general Felkin–Anh model. In particular, we have calculated that a twist-boat conformation is relevant to the reactivity and facial selectivity of hydride reduction of cis-2,6-disubstituted N-acylpiperidones with a small hydride reagent (LiAlH4) but not with a bulky hydride (lithium triisopropylborohydride). PMID:25372509

The synthesis and antistaphylococcal activity of 9, 13-disubstituted berberine derivatives.

PubMed

Wang, Jing; Yang, Teng; Chen, Huang; Xu, Yun-Nan; Yu, Li-Fang; Liu, Ting; Tang, Jie; Yi, Zhengfang; Yang, Cai-Guang; Xue, Wei; Yang, Fan

2017-02-15

A series of novel 9, 13-disubstituted berberine derivatives have been synthesized and evaluated for the antibacterial activities against Staphylococcus aureus, including Newman strain and multidrug-resistant strains (NRS-1, NRS-70, NRS-100, NRS-108, and NRS-271). Compound 20 shows the most potent activity against the growth of Newman strain, with a MIC value of 0.78 μg/mL, which is comparable with the positive control vancomycin. In addition, compound 20, 21, and 33 are highly antistaphylococcal active against five strains of multidrug-resistant S. aureus, with MIC values of 0.78-1.56 μg/mL. Of note, theses antibacterial active compounds have no obvious toxicity to the viability of human fibroblast (HAF) cells at the MIC concentration. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

3D-QSAR modeling and molecular docking studies on a series of 2,5 disubstituted 1,3,4-oxadiazoles

NASA Astrophysics Data System (ADS)

Ghaleb, Adib; Aouidate, Adnane; Ghamali, Mounir; Sbai, Abdelouahid; Bouachrine, Mohammed; Lakhlifi, Tahar

2017-10-01

3D-QSAR (comparative molecular field analysis (CoMFA)) and comparative molecular similarity indices analysis (CoMSIA) were performed on novel 2,5 disubstituted 1,3,4-oxadiazoles analogues as anti-fungal agents. The CoMFA and CoMSIA models using 13 compounds in the training set gives Q2 values of 0.52 and 0.51 respectively, while R2 values of 0.92. The adapted alignment method with the suitable parameters resulted in reliable models. The contour maps produced by the CoMFA and CoMSIA models were employed to determine a three-dimensional quantitative structure-activity relationship. Based on this study a set of new molecules with high predicted activities were designed. Surflex-docking confirmed the stability of predicted molecules in the receptor.

Chemical Kinetics Interpretation of Hypergolicity of Ionic Liquid-Based Systems

DTIC Science & Technology

2009-04-01

acid (WFNA) mixtures 6 4. Thermochemistry of imidazoles, triazoles and tetrazoles 8 5. Thermochemistry of compounds formed...reactivity of gaseous mixtures formed above ionic liquids (ILs) when mixed with white fuming nitric acid (WFNA). After a general introduction on the...replacement for NTO is also of interest but probably less crucial. For instance, NTO could be replaced by nitric acid (or by any other suitable

Two Zinc(II) metal-organic frameworks with mixed ligands of 5-amino-tetrazolate and l,2,4,5-benzenetetracarboxylate: Synthesis, structural diversity and photoluminescent properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Xiao-Bing; Lu, Wen-Guan, E-mail: lwg@sgu.edu.cn; Zhong, Di-Chang

The reactions of Zn(NO{sub 3}){sub 2}·6H{sub 2}O with mixed ligands of 5-amino-tetrazole (Hatz) and l,2,4,5-benzenetetracarboxylic acid (H{sub 4}btec) under hydro(solvo)thermal conditions, gave two three-dimensional (3D) porous metal-organic frameworks (MOFs) of ([Zn{sub 3}(atz){sub 2}(btec)(DMF){sub 2}]·DMF·2H{sub 2}O){sub n} (1) and [Zn{sub 2}(Hprz)(atz)(btec)(H{sub 2}O)]{sub n} (2) in the absence and presence of piperazine (prz), respectively. 1 and 2 were characterized by infrared spectra (IR), elemental analyses (EA) and single-crystal/powder X-ray diffraction. In 1, the adjacent 1D [Zn{sub 3}(btec)]{sub n}{sup 2n+} chains are linked together by atz{sup −} ligands to form a 3D porous MOF with 1D tetragonal channels filled with coordinated and guestmore » DMF, and lattice water molecules. In 2, the adjacent 2D [Zn{sub 2}(btec)]{sub n} wavelike sheets are pillared through atz{sup −} ligands to generate a 3D layered-pillared porous MOF with 1D open channels, which are occupied by coordinated Hprz{sup +} cations and coordinated water molecules. Additionally, thermal stabilities and photoluminescent properties of both compounds in the solid-state at room temperature have been investigated and discussed in detail. - Graphical abstract: Two new MOFs constructed from Zn(II) salts with mixed ligands of 5-amino-tetrazole and l,2,4,5-benzenetetracarboxylic acid were synthesized under different reaction conditions. Structural diversities indicate that the reaction solvent system or the presence of organic base play crucial roles in modulating structures of these compounds. And more, their thermal stability and luminescence are also discussed. - Highlights: • Two new Zn(II) MOFs based on mixed ligands were synthesized. • The two Zn(II) MOFs exhibit different structural motifs. • The two Zn(II) MOFs are photoluminscent in the solid state at room temperature.« less

Formal Synthesis of (±)-Roseophilin

PubMed Central

Bitar, Abdallah Y.; Frontier, Alison J.

2009-01-01

A formal synthesis of (±)-roseophilin is described. Scandium(III)-catalyzed Nazarov cyclization of 2,5-disubstituted N-tosylpyrrole 19 gives a 5,5’-fused ketopyrrole, and ansa-bridge formation via π-allyl palladium macrocyclization gives 21. PMID:19053717

1,5-Disubstituted benzimidazoles that direct cardiomyocyte differentiation from mouse embryonic stem cells.

PubMed

Okolotowicz, Karl J; Bushway, Paul; Lanier, Marion; Gilley, Cynthia; Mercola, Mark; Cashman, John R

2015-09-01

Cardiomyopathy is the leading cause of death worldwide. Despite progress in medical treatments, heart transplantation is one of the only current options for those with infarcted heart muscle. Stem cell differentiation technology may afford cell-based therapeutics that may lead to the generation of new, healthy heart muscle cells from undifferentiated stem cells. Our approach is to use small molecules to stimulate stem cell differentiation. Herein, we describe a novel class of 1,5-disubstituted benzimidazoles that induce differentiation of stem cells into cardiac cells. We report on the evaluation in vitro for cardiomyocyte differentiation and describe structure-activity relationship results that led to molecules with drug-like properties. The results of this study show the promise of small molecules to direct stem cell lineage commitment, to probe signaling pathways and to develop compounds for the stimulation of stem cells to repair damaged heart tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

A bioinspired catalytic aerobic oxidative C-H functionalization of primary aliphatic amines: synthesis of 1,2-disubstituted benzimidazoles.

PubMed

Nguyen, Khac Minh Huy; Largeron, Martine

2015-09-01

Aerobic oxidative CH functionalization of primary aliphatic amines has been accomplished with a biomimetic cooperative catalytic system to furnish 1,2-disubstituted benzimidazoles that play an important role as drug discovery targets. This one-pot atom-economical multistep process, which proceeds under mild conditions, with ambient air and equimolar amounts of each coupling partner, constitutes a convenient environmentally friendly strategy to functionalize non-activated aliphatic amines that remain challenging substrates for non-enzymatic catalytic aerobic systems. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of Creative Commons Attribution NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

1,5-Disubstituted benzimidazoles that direct cardiomyocyte differentiation from mouse embryonic stem cells

PubMed Central

Okolotowicz, Karl J.; Bushway, Paul; Lanier, Marion; Gilley, Cynthia; Cynthia, Mark; Cashman, John R.

2016-01-01

Cardiomyopathy is the leading cause of death worldwide. Despite progress in medical treatments, heart transplantation is one of the only current options for those with infarcted heart muscle. Stem cell differentiation technology may afford cell-based therapeutics that may lead to the generation of new, healthy heart muscle cells from undifferentiated stem cells. Our approach is to use small molecules to stimulate stem cell differentiation. Herein, we describe a novel class of 1,5-disubstituted benzimidazoles that induce differentiation of stem cells into cardiac cells. We report on the evaluation in vitro for cardiomyocyte differentiation and describe structure–activity relationship results that led to molecules with drug-like properties. The results of this study show the promise of small molecules to direct stem cell lineage commitment, to probe signaling pathways and to develop compounds for the stimulation of stem cells to repair damaged heart tissue. PMID:26278027

Replacement of the lactone moiety on podophyllotoxin and steganacin analogues with a 1,5-disubstituted 1,2,3-triazole via ruthenium-catalyzed click chemistry.

PubMed

Imperio, Daniela; Pirali, Tracey; Galli, Ubaldina; Pagliai, Francesca; Cafici, Laura; Canonico, Pier Luigi; Sorba, Giovanni; Genazzani, Armando A; Tron, Gian Cesare

2007-11-01

Steganacin and podophyllotoxin are two naturally occurring lignans first isolated from plant sources, which share the capability to disrupt tubulin assembly. Although not strictly essential for its activity, the lactone ring on both structures represents Achilles' heel, as it is a potential site of metabolic degradation and epimerization on its C2 carbon brings about a significant loss in potency. In the present manuscript, we have used the ruthenium-catalyzed [3+2] azide-alkyne cycloaddition, a click-chemistry reaction, to replace the lactone ring with a 1,5-disubstituted triazole in few synthetic steps. The compounds were cytotoxic, although to a lesser degree compared to podophyllotoxin, while retaining antitubulin activity. The present structures might therefore represent a good platform for the fast generation of metabolically stable compounds with few stereogenic centers that might be of value from a medicinal chemistry point of view.

Influence of hydroxylamine conformation on stereocontrol in Pd-catalyzed isoxazolidine-forming reactions.

PubMed

Lemen, Georgia S; Giampietro, Natalie C; Hay, Michael B; Wolfe, John P

2009-03-20

Palladium-catalyzed carboamination reactions between N-Boc-O-(but-3-enyl)hydroxylamine derivatives and aryl or alkenyl bromides afford cis-3,5- and trans-4,5-disubstituted isoxazolidines in good yield with up to >20:1 dr. The diastereoselectivity observed in the formation of cis-3,5-disubstituted isoxazolidines is superior to selectivities typically obtained in other transformations, such as 1,3-dipolar cycloaddition reactions, that provide these products. In addition, the stereocontrol in the C-N bond-forming Pd-catalyzed carboamination reactions of N-Boc-O-(but-3-enyl)hydroxylamines is significantly higher than that of related C-O bond-forming carboetherification reactions of N-benzyl-N-(but-3-enyl)hydroxylamine derivatives. This is likely due to a stereoelectronic preference for cyclization via transition states in which the Boc group is placed in a perpendicular orientation relative to the plane of the developing ring, which derives from the conformational equilibria of substituted hydroxylamines.

Phosphine-Catalyzed Doubly Stereoconvergent γ-Additions of Racemic Heterocycles to Racemic Allenoates: The Catalytic Enantioselective Synthesis of Protected α,α-Disubstituted α-Amino Acid Derivatives.

PubMed

Kalek, Marcin; Fu, Gregory C

2015-07-29

Methods have recently been developed for the phosphine-catalyzed asymmetric γ-addition of nucleophiles to readily available allenoates and alkynoates to generate useful α,β-unsaturated carbonyl compounds that bear a stereogenic center in either the γ or the δ position (but not both) with high stereoselectivity. The utility of this approach would be enhanced considerably if the stereochemistry at both termini of the new bond could be controlled effectively. In this report, we describe the achievement of this objective, specifically, that a chiral phosphepine can catalyze the stereoconvergent γ-addition of a racemic nucleophile to a racemic electrophile; through the choice of an appropriate heterocycle as the nucleophilic partner, this new method enables the synthesis of protected α,α-disubstituted α-amino acid derivatives in good yield, diastereoselectivity, and enantioselectivity.

N,N'-disubstituted cinnamamide derivatives potentiate ciprofloxacin activity against overexpressing NorA efflux pump Staphylococcus aureus 1199B strains.

PubMed

Radix, Sylvie; Jordheim, Anne Doléans; Rocheblave, Luc; N'Digo, Serge; Prignon, Anne-Laure; Commun, Carine; Michalet, Serge; Dijoux-Franca, Marie-Geneviève; Mularoni, Angélique; Walchshofer, Nadia

2018-04-25

A multi-step procedure has been described which afforded satisfactory yields of N,N'-disubstituted cinnamamides derived from N-Boc-protected amino acids (Boc-Gly, Boc-Val, Boc-Phe). The key step of this synthesis was a regioselective RedAl reduction of an amide function in presence of a carbamate group. Next, these cinnamamides were evaluated in co-admnistration with ciprofloxacin as efflux pump inhibitors against two S. aureus strains, NorA overexpressing SA1199B and wild type SA1199. In parallel, their intrinsic toxicity was appreciated on human lung fibroblast MRC5 cells. Therefore, the cinnamamide combining both carbamate and indol-3-yl groups, was found to be the most active and one of the less toxic EPI and constituted a promising hit. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Carbopalladation of nitriles: synthesis of 3,4-disubstituted 2-aminonaphthalenes and 1,3-benzoxazine derivatives by the palladium-catalyzed annulation of alkynes by (2-Iodophenyl)acetonitrile.

PubMed

Tian, Qingping; Pletnev, Alexandre A; Larock, Richard C

2003-01-24

Intramolecular carbopalladation of the cyano group has been employed for the synthesis of 3,4-disubstituted 2-aminonaphthalenes. (2-Iodophenyl)acetonitrile reacts with a variety of internal alkynes to afford 2-aminonaphthalenes in high yields with good regioselectivity. The scope and limitations of this process, which proceeds by the intramolecular addition of a vinylpalladium species to the triple bond of the cyano group, have been studied. The annulation of certain hindered propargylic alcohols affords 1,3-benzoxazine derivatives, rather than the expected 2-aminonaphthalenes. The involvement of trialkylamine bases in the formation of these heterocyclic compounds has been established. A proposed mechanism for the synthesis of 1,3-benzoxazine derivatives involves the formation of the expected 2-amino-3-(1-hydroxyalkyl)naphthalenes, followed by their condensation with an iminium ion species formed from the trialkylamine base used in the reaction.

Environmentally Acceptable Medium Caliber Ammunition Percussion Primers

DTIC Science & Technology

2007-10-31

tetrazol-5-amino)-s-tetrazine or Bis-aminotetrazolyl-tetrazine CAD Cartridge Actuated Device CFR Code of Federal Regulations cm Centimeter cm3...approximately 120mg each, were placed on the Plexiglas slab . The piles were separated by a potassium chloride window estimated to transmit at least...for cartridge actuated device/propellant actuated device ( CAD /PAD) application. The NSWC-IH was working with the SDSMT and IMP in developing unique

o-Iodoxybenzoic acid mediated oxidative desulfurization initiated domino reactions for synthesis of azoles.

PubMed

Chaudhari, Pramod S; Pathare, Sagar P; Akamanchi, Krishnacharaya G

2012-04-20

A systematic exploration of thiophilic ability of o-iodoxybenzoic acid (IBX) for oxidative desulfurization to trigger domino reactions leading to new methodologies for synthesis of different azoles is described. A variety of highly substituted oxadiazoles, thiadiazoles, triazoles, and tetrazoles have been successfully synthesized in good to excellent yields, starting from readily accessible thiosemicarbazides, bis-diarylthiourea, 1,3-disubtituted thiourea, and thioamides. © 2012 American Chemical Society

Applications of High-Nitrogen Energetics in Pyrotechnics: Development of Perchlorate-Free Red Star M126A1 Hand-Held Signal Formulations with Superior Luminous Intensities and Burn Times

DTIC Science & Technology

2011-03-25

short-term administration of 3-amino- triazole. The US Army Public Health Command has stated that quantitative structure activity relationship ( QSAR ...modeling is not a useful tool in determining the toxic nature of high nitrogen salts such as bis-tetrazolate 1. Therefore, no data on the toxicology of

JPRS Report, Science & Technology USSR: Chemistry

DTIC Science & Technology

1991-08-12

KH1M1CHESKIKHNAUK No 1 , Jan-Feb 91] 18 Synthesis of Neodymium Silicates and Glass Prepared From Them by Laser Irradiation of Co-Precipitated...KHIMICHESKIY ZHURNAL No 1 , Jan-Feb 91] 28 Synthesis and Investigation of Antiarrhythmic Activity of Alkoxyaminoalcohol Salts of Cyclohexane Series [N.S...Catalysts in Organic Synthesis . Communication 25. Synthesis of Polymer Supported Tetrazols 917M0091D Riga LATVIYSKIY KHIMICHESKIY ZHURNAL in Russian No 1

O-nitroso aldol synthesis: Catalytic enantioselective route to α-aminooxy carbonyl compounds via enamine intermediate

PubMed Central

Momiyama, Norie; Torii, Hiromi; Saito, Susumu; Yamamoto, Hisashi

2004-01-01

The approach using pyrrolidine enamine as substrate has been studied for this synthesis, and an important catalyst structural feature has been developed. After survey of pyrrolidine-based Brønsted acid catalyst, tetrazole catalyst (3f) was found to be optimal in synthesis of aminooxy carbonyl compounds in high yields, with complete enantioselectivity not only for aldehydes but also for ketones. PMID:15067138

Toward a Modular Ionic Liquid Platform for the Custom Design of Energetic Materials: Understanding How the Dual Nature of Ionic Liquids Relates Key Physical Properties to Target Structures

DTIC Science & Technology

2009-11-30

cations were obtained and isolated with a diverse group of azolate anions including nitro- substituted benzotriazolate, benzimidazolate , 1,2,4-triazolate... benzimidazolate , or benzotrizolate) have received much less attention than those containing azolium cations, although more results are now starting to...phosphonium cations combined with energetically-substituted tetrazolate, triazolate, imidazolate, benzimidazolate , and benzotriazolate anions (Figure

COMPUTATIONAL ELECTROCHEMISTRY: AQUEOUS ONE-ELECTRON OXIDATION POTENTIALS FOR SUBSTITUTED ANILINES

EPA Science Inventory

Semiempirical molecular orbital theory and density functional theory are used to compute one-electron oxidation potentials for aniline and a set of 21 mono- and di-substituted anilines in aqueous solution. Linear relationships between theoretical predictions and experiment are co...

Rational design, synthesis and biological screening of triazine-triazolopyrimidine hybrids as multitarget anti-Alzheimer agents.

PubMed

Jameel, Ehtesham; Meena, Poonam; Maqbool, Mudasir; Kumar, Jitendra; Ahmed, Waqar; Mumtazuddin, Syed; Tiwari, Manisha; Hoda, Nasimul; Jayaram, B

2017-08-18

In our endeavor towards the development of potent multitarget ligands for the treatment of Alzheimer's disease, a series of triazine-triazolopyrimidine hybrids were designed, synthesized and characterized by various spectral techniques. Docking and scoring techniques were used to design the inhibitors and to display their interaction with key residues of active site. Organic synthesis relied upon convergent synthetic routes were mono and di-substituted triazines were connected with triazolopyrimidine using piperazine as a linker. In total, seventeen compounds were synthesized in which the di-substituted triazine-triazolopyrimidine derivatives 9a-d showed better acetylcholinesterase (AChE) inhibitory activity than the corresponding tri-substituted triazine-triazolopyrimidine derivatives 10a-f. Out of the disubstituted triazine-triazolopyrimidine based compounds, 9a and 9b showed encouraging inhibitory activity on AChE with IC 50 values 0.065 and 0.092 μM, respectively. Interestingly, 9a and 9b also demonstrated good inhibition selectivity towards AChE over BuChE by ∼28 folds. Furthermore, kinetic analysis and molecular modeling studies showed that 9a and 9b target both catalytic active site as well as peripheral anionic site of AChE. In addition, these derivatives effectively modulated Aβ self-aggregation as investigated through CD spectroscopy, ThT fluorescence assay and electron microscopy. Besides, these compounds exhibited potential antioxidants (2.15 and 2.91 trolox equivalent by ORAC assay) and metal chelating properties. In silico ADMET profiling highlighted that, these novel triazine derivatives have appropriate drug like properties and possess very low toxic effects in the primarily pharmacokinetic study. Overall, the multitarget profile exerted by these novel triazine molecules qualified them as potential anti-Alzheimer drug candidates in AD therapy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Conformational restriction through C alpha i <--> C alpha i cyclization: Ac12c, the largest cycloaliphatic C alpha,alpha- disubstituted glycine known.

PubMed

Saviano, M; Iacovino, R; Menchise, V; Benedetti, E; Bonora, G M; Gatos, M; Graci, L; Formaggio, F; Crisma, M; Toniolo, C

2000-02-01

Two complete series of N-protected, monodispersed oligopeptide esters to the pentamer level from 1-aminocyclododecane-1-carboxylic acid (Ac(12)c), an alpha-amino acid conformationally constrained through C(alpha)(i) <--> C(alpha)(i) cyclization, and either L-Ala or Aib residues, along with the N-protected Ac(12)c homopeptide alkylamide series from monomer to trimer, have been synthesized by solution methods and fully characterized. The solution-preferred conformations of these peptides have been assessed by Fourier transform ir absorption and (1)H-nmr techniques. Moreover, the molecular structures of one derivative (Z-Ac(12)c-OH) and three peptides [the tripeptide ester Z-L-Ala-Ac(12)c-L-Ala-OMe, the tripeptide alkylamide Z-(Ac(12)c)(3)-NHiPr, and the tetrapeptide ester Z-(Aib)(2)-Ac(12)c-Aib-OtBu (Aib, alpha-aminoisobutyric acid)] have been determined in the crystal state by x-ray diffraction. The results obtained point to the conclusion that beta-bends and 3(10)-helices are preferentially adopted by peptides based on Ac(12)c, the largest cycloaliphatic C-disubstituted glycine known. A comparison with the structural tendencies extracted from published works on peptides from Aib, the prototype of C-disubstituted glycines, and the other extensively studied members of the class of 1-aminocycloalkane-1-carboxylic acids (Ac(n) c, with n = 3-9), is made and the implications for the use of the Ac(12)c residue in the Ac(n) c scan approach of conformationally restricted analogues of bioactive peptides are briefly discussed. Copyright 2000 John Wiley & Sons, Inc.

IMMUNE FUNCTION IN ADULT RATS EXPOSED TO DBT IN DRINKING WATER

EPA Science Inventory

Organotins are used commercially as agricultural pesticides, antifouling agents and stabilizers for polyvinyl chloride (PVC) pipe. Mono- and di-substituted methyl and butyltins, used in PVC pipe production, are of concern to the USEPA as they leach from supply pipes into drinking...

IMMUNE FUNCTION IN RATS DEVELOPMENTALLY EXPOSED TO DIBUTYLTIN DICHLORIDE

EPA Science Inventory

Organotins are used commercially as pesticides, antifouling agents and stabilizers for polyvinyl chloride (PVC) pipe. Mono- and di-substituted methyl and butyltins, used in PVC pipe production, are of concern to the USEPA as they leach from supply pipes into drinking water and ha...

BROMOCHLOROACETIC ACID EXERTS QUALITATIVE EFFECTS ON RAT SPERM: IMPLICATIONS FOR A NOVEL BIOMARKER

EPA Science Inventory

ABSTRACT
Disubstituted haloacid by-products of drinking water disinfection such as dibromoacetic acid and dichloroacetic acid have been shown to perturb spermatogenesis and fertility in adult male rats. In the present study we sought to establish whether equimolar exposur...

1,2-disubstituted ferrocenyl carbohydrate chloroquine conjugates as potential antimalarial agents.

PubMed

Herrmann, Christoph; Salas, Paloma F; Patrick, Brian O; de Kock, Carmen; Smith, Peter J; Adam, Michael J; Orvig, Chris

2012-06-07

This work presents a new family of organometallic antimalarial compounds consisting of ferrocene bearing a chloroquine-derived moiety as well as a 1,2;3,5-diisopropylidene glucofuranose moiety at a cyclopentadienyl scaffold in a 1,2-substitution pattern. The synthetic route proceeds via a stereoselective functionalization of ferrocene carboxaldehyde to the 1,2-disubstituted conjugates. After complete characterization of these new, trifunctional conjugates, they were examined for their cytotoxicity in two cancerous cell lines (MDA-MB-435S and Caco2) and one non-cancerous cell line (MCF-10A), showing that increased cytotoxicity can be observed for the chloroquine ferrocenyl conjugates compared to their carbohydrate-substituted precursors. The antiplasmodial activity of the conjugates in a chloroquine-sensitive strain of Plasmodium falciparum (D10) and a chloroquine-resistant strain (Dd2) was determined. Monosubstituted conjugates 13, 14 and 15 exhibit decreasing activity with increasing alkyl chain length between the ferrocene and quinoline moiety, bifunctional conjugates 16, 17, 18 show constant activity, performing better than chloroquine in the Dd2 strain.

Synthesis and structure-activity relationships of novel cationic lipids with anti-inflammatory and antimicrobial activities.

PubMed

Myint, Melissa; Bucki, Robert; Janmey, Paul A; Diamond, Scott L

2015-07-15

Certain membrane-active cationic steroids are known to also possess both anti-inflammatory and antimicrobial properties. This combined functionality is particularly relevant for potential therapies of infections associated with elevated tissue damage, for example, cystic fibrosis airway disease, a condition characterized by chronic bacterial infections and ongoing inflammation. In this study, six novel cationic glucocorticoids were synthesized using beclomethasone, budesonide, and flumethasone. Products were either monosubstituted or disubstituted, containing one or two steroidal groups, respectively. In vitro evaluation of biological activities demonstrated dual anti-inflammatory and antimicrobial properties with limited cytotoxicity for all synthesized compounds. Budesonide-derived compounds showed the highest degree of both glucocorticoid and antimicrobial properties within their respective mono- and disubstituted categories. Structure-activity analyses revealed that activity was generally related to the potency of the parent glucocorticoid. Taken together, these data indicate that these types of dual acting cationic lipids can be synthesized with the appropriate starting steroid to tailor activities as desired. Copyright © 2015 Elsevier Ltd. All rights reserved.

Silicon Phthalocyanines Axially Disubstituted with Erlotinib toward Small-Molecular-Target-Based Photodynamic Therapy.

PubMed

Chen, Juan-Juan; Huang, Yi-Zhen; Song, Mei-Ru; Zhang, Zhi-Hong; Xue, Jin-Ping

2017-09-21

Small-molecular-target-based photodynamic therapy-a promising targeted anticancer strategy-was developed by conjugating zinc(II) phthalocyanine with a small-molecular-target-based anticancer drug. To prevent self-aggregation and avoid problems of phthalocyanine isomerization, two silicon phthalocyanines di-substituted axially with erlotinib have been synthesized and fully characterized. These conjugates are present in monomeric form in various solvents as well as culture media. Cell-based experiments showed that these conjugates localize in lysosomes and mitochondria, while maintaining high photodynamic activities (IC 50 values as low as 8 nm under a light dose of 1.5 J cm -2 ). With erlotinib as the targeting moiety, two conjugates were found to exhibit high specificity for EGFR-overexpressing cancer cells. Various poly(ethylene glycol) (PEG) linker lengths were shown to have an effect on the photophysical/photochemical properties and on in vitro phototoxicity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Z-Selective Catalytic Olefin Cross-Metathesis

PubMed Central

Meek, Simon J.; O’Brien, Robert V.; Llaveria, Josep; Schrock, Richard R.; Hoveyda, Amir H.

2011-01-01

Alkenes are found in a great number of biologically active molecules and are employed in numerous transformations in organic chemistry. Many olefins exist as E or higher energy Z isomers. Catalytic procedures for stereoselective formation of alkenes are therefore valuable; nonetheless, methods for synthesis of 1,2-disubstituted Z olefins are scarce. Here we report catalytic Z-selective cross-metathesis reactions of terminal enol ethers, which have not been reported previously, and allylic amides, employed thus far only in E-selective processes; the corresponding disubstituted alkenes are formed in up to >98% Z selectivity and 97% yield. Transformations, promoted by catalysts that contain the highly abundant and inexpensive molybdenum, are amenable to gram scale operations. Use of reduced pressure is introduced as a simple and effective strategy for achieving high stereoselectivity. Utility is demonstrated by syntheses of anti-oxidant C18 (plasm)-16:0 (PC), found in electrically active tissues and implicated in Alzheimer’s disease, and the potent immunostimulant KRN7000. PMID:21430774

An efficient synthesis of a rationally designed 1,5 disubstituted imidazole AT(1) angiotensin II receptor antagonist: reorientation of imidazole pharmacophore groups in losartan reserves high receptor affinity and confirms docking studies.

PubMed

Agelis, George; Roumelioti, Panagiota; Resvani, Amalia; Durdagi, Serdar; Androutsou, Maria-Eleni; Kelaidonis, Konstantinos; Vlahakos, Demetrios; Mavromoustakos, Thomas; Matsoukas, John

2010-09-01

A new 1,5 disubstituted imidazole AT(1) Angiotensin II (AII) receptor antagonist related to losartan with reversion of butyl and hydroxymethyl groups at the 2-, 5-positions of the imidazole ring was synthesized and evaluated for its antagonist activity (V8). In vitro results indicated that the reorientation of butyl and hydroxymethyl groups on the imidazole template of losartan retained high binding affinity to the AT(1) receptor concluding that the spacing of the substituents at the 2,5- positions is of primary importance. The docking studies are confirmed by binding assay results which clearly show a comparable binding score of the designed compound V8 with that of the prototype losartan. An efficient, regioselective and cost effective synthesis renders the new compound as an attractive candidate for advanced toxicological evaluation and a drug against hypertension.

An efficient synthesis of a rationally designed 1,5 disubstituted imidazole AT1 Angiotensin II receptor antagonist: reorientation of imidazole pharmacophore groups in losartan reserves high receptor affinity and confirms docking studies

NASA Astrophysics Data System (ADS)

Agelis, George; Roumelioti, Panagiota; Resvani, Amalia; Durdagi, Serdar; Androutsou, Maria-Eleni; Kelaidonis, Konstantinos; Vlahakos, Demetrios; Mavromoustakos, Thomas; Matsoukas, John

2010-09-01

A new 1,5 disubstituted imidazole AT1 Angiotensin II (AII) receptor antagonist related to losartan with reversion of butyl and hydroxymethyl groups at the 2-, 5-positions of the imidazole ring was synthesized and evaluated for its antagonist activity ( V8). In vitro results indicated that the reorientation of butyl and hydroxymethyl groups on the imidazole template of losartan retained high binding affinity to the AT1 receptor concluding that the spacing of the substituents at the 2,5- positions is of primary importance. The docking studies are confirmed by binding assay results which clearly show a comparable binding score of the designed compound V8 with that of the prototype losartan. An efficient, regioselective and cost effective synthesis renders the new compound as an attractive candidate for advanced toxicological evaluation and a drug against hypertension.

Quantitative investigations of xylose and arabinose substituents in hydroxypropylated and hydroxyvinylethylated arabinoxylans.

PubMed

Lorenz, Dominic; Knöpfle, Anna; Akil, Youssef; Saake, Bodo

2017-11-01

The chemical structures obtained by the modification of arabinoxylans with the cyclic carbonates propylene carbonate (PC) and 4-vinyl-1,3-dioxolan-2-one (VEC) with varying degrees of substitution were investigated. Therefore, a new analytical method was developed that is based on a microwave-assisted hydrolysis of the polysaccharides with trifluoroacetic acid and the reductive amination with 2-aminobenzoic acid. The peak assignment was achieved by HPLC-MS and the carbohydrate derivatives were quantified by HPLC-fluorescence. The obtained maximum molar substitution of PC-derivatized xylan (X HP ) was 1.8; the molar substitution of VEC-derivatized xylan (X HVE ) was 2.3. Investigations of xylose and arabinose based mono- and disubstituted derivatives revealed a preferred reaction of the cyclic carbonates with arabinose. Conversion rates were up to 2.4 times higher for monosubstitution and up to 3.0 times for disubstitution compared to xylose. Furthermore, the reaction with VEC was preferred due to higher reactivity of the newly introduced side chains. Copyright © 2017 Elsevier Ltd. All rights reserved.

Metabolism of a new P-glycoprotein inhibitor HM-30181 in rats using liquid chromatography/electrospray mass spectrometry.

PubMed

Paek, In Bok; Ji, Hye Young; Kim, Maeng Sup; Lee, Gwansun; Lee, Hye Suk

2006-01-01

HM-30181, 4-oxo-4H-chromene-2-carboxylic acid, [2-(2-{4-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]-phenyl}-2H-tetrazol-5-yl)-4,5-dimethoxyphenyl]amide, is a new P-glycoprotein inhibitor. This study was performed to identify the in vitro and in vivo metabolic pathway of HM-30181 in rats. Rat liver microsomal incubation of HM-30181 in the presence of NADPH resulted in the formation of four metabolites, M1-M4. M1 and M2 were identified as 2-(2-{4-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]-phenyl}-2H-tetrazol-5-yl)-4,5-dimethoxyaniline and 4- or 5-O-desmethyl-HM-30181, respectively, on the basis of liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis with the synthesized authentic standards. M3 and M4 were suggested to be 6- or 7-O-desmethyl-HM-30181 and hydroxy-HM-30181, respectively. These in vitro metabolites were also detected in feces and urine samples after an intravenous administration of HM-30181 to male rats. The metabolic routes for HM-30181 were O-demethylation of the methoxy group to M2 and M3, hydrolysis of the amide group to M1, and hydroxylation to M4. Copyright 2006 John Wiley & Sons, Ltd.

Nitrogen-Rich Energetic Metal-Organic Framework: Synthesis, Structure, Properties, and Thermal Behaviors of Pb(II) Complex Based on N,N-Bis(1H-tetrazole-5-yl)-Amine

PubMed Central

Liu, Qiangqiang; Jin, Bo; Zhang, Qingchun; Shang, Yu; Guo, Zhicheng; Tan, Bisheng; Peng, Rufang

2016-01-01

The focus of energetic materials is on searching for a high-energy, high-density, insensitive material. Previous investigations have shown that 3D energetic metal–organic frameworks (E-MOFs) have great potential and advantages in this field. A nitrogen-rich E-MOF, Pb(bta)·2H2O [N% = 31.98%, H2bta = N,N-Bis(1H-tetrazole-5-yl)-amine], was prepared through a one-step hydrothermal reaction in this study. Its crystal structure was determined through single-crystal X-ray diffraction, Fourier transform infrared spectroscopy, and elemental analysis. The complex has high heat denotation (16.142 kJ·cm−3), high density (3.250 g·cm−3), and good thermostability (Tdec = 614.9 K, 5 K·min−1). The detonation pressure and velocity obtained through theoretical calculations were 43.47 GPa and 8.963 km·s−1, respectively. The sensitivity test showed that the complex is an impact-insensitive material (IS > 40 J). The thermal decomposition process and kinetic parameters of the complex were also investigated through thermogravimetry and differential scanning calorimetry. Non-isothermal kinetic parameters were calculated through the methods of Kissinger and Ozawa-Doyle. Results highlighted the nitrogen-rich MOF as a potential energetic material. PMID:28773805

Characterization of Two Distinct Amorphous Forms of Valsartan by Solid-State NMR.

PubMed

Skotnicki, Marcin; Apperley, David C; Aguilar, Juan A; Milanowski, Bartłomiej; Pyda, Marek; Hodgkinson, Paul

2016-01-04

Valsartan (VAL) is an antihypertensive drug marketed in an amorphous form. Amorphous materials can have different physicochemical properties depending on preparation method, thermal history, etc., but the nature of such materials is difficult to study by diffraction techniques. This study characterizes two different amorphous forms of valsartan (AR and AM) using solid-state NMR (SSNMR) as a primary investigation tool, supported by solution-state NMR, FT-IR, TMDSC, and dissolution tests. The two forms are found to be clearly distinct, with a significantly higher level of structural arrangement in the AR form, as observed in (13)C, (15)N, and (1)H SSNMR. (13)C and (15)N NMR indicates that the fully amorphous material (AM) contains an approximately equal ratio of cis-trans conformers about the amide bond, whereas the AR form exists mainly as one conformer, with minor conformational "defects". (1)H ultrafast MAS NMR shows significant differences in the hydrogen bonding involving the tetrazole and acid hydrogens between the two materials, while (15)N NMR shows that both forms exist as a 1,2,3,4-tetrazole tautomer. NMR relaxation times show subtle differences in local and bulk molecular mobility, which can be connected with the glass transition, the stability of the glassy material, and its response to aging. Counterintuitively the fully amorphous material is found to have a significantly lower dissolution rate than the apparently more ordered AR material.

A microwave assisted intramolecular-furan-Diels-Alder approach to 4-substituted indoles.

PubMed

Petronijevic, Filip; Timmons, Cody; Cuzzupe, Anthony; Wipf, Peter

2009-01-07

The key steps of a versatile new protocol for the convergent synthesis of 3,4-disubstituted indoles are the addition of an alpha-lithiated alkylaminofuran to a carbonyl compound, a microwave-accelerated intramolecular Diels-Alder cycloaddition and an in situ double aromatization reaction.

Computational Analysis of Stereospecificity in the Cope Rearrangement

ERIC Educational Resources Information Center

Glish, Laura; Hanks, Timothy W.

2007-01-01

The Cope rearrangement is a highly stereospecific, concerted reaction of considerable synthetic utility. Experimental product distributions from the reaction of disubstituted 1,5-hexadienes can be readily understood by computer modeling of the various possible transitions states. Semi-empirical methods give relative energies of transition states…

Flexible synthesis of poison-frog alkaloids of the 5,8-disubstituted indolizidine-class. II: Synthesis of (-)-209B, (-)-231C, (-)-233D, (-)-235B", (-)-221I, and an epimer of 193E and pharmacological effects at neuronal nicotinic acetylcholine receptors.

PubMed

Kobayashi, Soushi; Toyooka, Naoki; Zhou, Dejun; Tsuneki, Hiroshi; Wada, Tsutomu; Sasaoka, Toshiyasu; Sakai, Hideki; Nemoto, Hideo; Garraffo, H Martin; Spande, Thomas F; Daly, John W

2007-01-01

The 5,8-disubstituted indolizidines constitute the largest class of poison-frog alkaloids. Some alkaloids have been shown to act as noncompetitive blockers at nicotinic acetylcholine receptors but the proposed structures and the biological activities of most of the 5,8-disubstituted indolizidines have not been determined because of limited supplies of the natural products. We have therefore conducted experiments to confirm proposed structures and determine biological activities using synthetic compounds. Recently, we reported that one of this class of alkaloids, (-)-235B', acts as a noncompetitive antagonist for α4β2 nicotinic receptors, and its sensitivity is comparable to that of the classical competitive antagonist for this receptor, dihydro-β-erythroidine. The enantioselective syntheses of (-)-209B, (-)-231C, (-)-233D, (-)-235B", (-)-221I, and what proved to be an epimer of natural 193E, starting from common chiral lactams have been achieved. When we performed electrophysiological recordings to examine the effects of the synthetic alkaloids on two major subtypes of nicotinic receptors (α4β2 and α7) expressed in Xenopus laevis oocytes, (-)-231C effectively blocked α4β2 receptor responses (IC(50 )value, 1.5 μM) with a 7.0-fold higher potency than for blockade of α7 receptor responses. In contrast, synthetic (-)-221I and (-)-epi-193E were more potent in blocking α7 receptor responses (IC(50 )value, 4.4 μM and 9.1 μM, respectively) than α4β2 receptor responses (5.3-fold and 2.0-fold, respectively). We achieved the total synthesis of (-)-209B, (-)-231C, (-)-233D, (-)-235B", (-)-221I, and an epimer of 193E starting from common chiral lactams, and the absolute stereochemistry of natural (-)-233D was determined. Furthermore, the relative stereochemistry of (-)-231C and (-)-221I was also determined. The present asymmetric synthesis of the proposed structure for 193E revealed that the C-8 configuration of natural 193E should be revised. The selectivity for α4β2 and α7 nicotinic receptors differed markedly for the 5,8-disubstituted indolizidines tested, and thus it appears that the nature of the side chains in these indolizidines is crucial with regard to subtype-selectivity.

40 CFR 721.7220 - Polymer of substituted phenol, formaldehyde, epichlorohydrin, and disubstituted benzene.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Polymer of substituted phenol... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.7220 Polymer of substituted phenol... subject to reporting. (1) The chemical substance identified generically as polymer of substituted phenol...

IMMUNE RESPONSES IN SPRAGUE-DAWLEY RATS EXPOSED TO DIBUTYLTIN DICHLORIDE IN DRINKING WATER AS ADULTS

EPA Science Inventory

Organotins are used commercially as agricultural pesticides, antifouling agents and stabilizers for

polyvinyl chloride (PVC) pipe. Mono- and di-substituted methyl and butyltins, used in PVC

pipe production, are of concern as they leach from supply pipes into drinkin...

DEVELOPMENTAL EXPOSURE TO DI-N-BUTYLTIN DICHLORIDE (DBTC): IMMUNOTOXIC AND NEUROTOXIC EVALUATION

EPA Science Inventory

Organotins are incorporated as stabilizers in PVC water supply pipe. Particularly when new, mono- and di-substituted methyl- and butyltins leach from the pipe and are thus of regulatory concern to EPA. These contaminants have adverse effects on both the immune and nervous systems...

A microwave assisted intramolecular-furan-Diels–Alder approach to 4-substituted indoles†

PubMed Central

Petronijevic, Filip; Timmons, Cody; Cuzzupe, Anthony; Wipf, Peter

2009-01-01

The key steps of a versatile new protocol for the convergent synthesis of 3,4-disubstituted indoles are the addition of an α-lithiated alkylaminofuran to a carbonyl compound, a microwave-accelerated intramolecular Diels–Alder cycloaddition and an in situ double aromatization reaction. PMID:19082013

Developing Ionic Liquid Know-How for the Design of Modular Functionality, Versatile Platforms, and New Synthetic Methodologies for Energetic Materials

DTIC Science & Technology

2013-12-05

Protocol for the Synthesis of Alkylated Imidazolium Salt Derivatives 1,3-Dimethylimidazolium chloride (1,3-diMe-IM][Cl]) (19c) and 1,2,3...C5’). A8. Hypergolic Ionic Liquids to Mill, Suspend, and Ignite Boron Nanoparticles Synthesis of 1-Butyl-3-methylimidazolium chloride ([1-Bu...3-methylimidazolium chloride , 5[Cl] D5. Zinc-assisted synthesis of imidazolium-tetrazolate bi-heterocyclic zwitterions with variable alkyl

An Active Insect Kinin Analog with 4-Aminopyroglutamate, A Novel cis-Peptide Bond, Type VI beta-Turn Motif

DTIC Science & Technology

2004-01-01

2004 Wiley Periodicals, Inc.* Biopolymers 75: 412–419, 2004 Keywords: 4-aminopyroglutamic acid ; cis-peptide bond; -turn mimetic; constrained insect...biological evaluation of an insect kinin analog containing a novel, (2S,4S)-4-aminopyroglutamic acid (APy) com- ponent (Figure 1) that theoretical and...cricket diuretic bioassay system. FIGURE 1 A comparison of the structures of the tetrazole ([CN4], left) and 4-aminopyroglu- tamic acid (APy; right

Ab initio Kinetics and Thermal Decomposition Mechanism of Mononitrobiuret and 1,5-Dinitrobiuret

DTIC Science & Technology

2016-03-14

Journal Article 3. DATES COVERED (From - To) Feb 2015-May 2015 4. TITLE AND SUBTITLE Ab initio Kinetics and Thermal Decomposition Mechanism of 5a...tetrazole-free, nitrogen-rich, energetic compounds. For the first time, the thermal decomposition mechanisms of MNB and DNB have been investigated...potential energy surfaces for thermal decomposition of MNB and DNB were characterized at the RCCSD(T)/cc-pV∞Z//M06-2X/aug- cc-pVTZ level of theory

Synthesis and P1' SAR exploration of potent macrocyclic tissue factor-factor VIIa inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ladziata, Vladimir; Glunz, Peter W.; Zou, Yan

Selective tissue factor-factor VIIa complex (TF-FVIIa) inhibitors are viewed as promising compounds for treating thrombotic disease. In this contribution, we describe multifaceted exploratory SAR studies of S1'-binding moieties within a macrocyclic chemotype aimed at replacing cyclopropyl sulfone P1' group. Over the course of the optimization efforts, the 1-(1H-tetrazol-5-yl)cyclopropane P1' substituent emerged as an improved alternative, offering increased metabolic stability and lower clearance, while maintaining excellent potency and selectivity.

Can conventional bases and unsaturated hydrocarbons be converted into gas-phase superacids that are stronger than most of the known oxyacids? The role of beryllium bonds.

PubMed

Yáñez, Manuel; Mó, Otilia; Alkorta, Ibon; Elguero, José

2013-08-26

The association of BeX2 (X: H, F, Cl) derivatives with azoles leads to a dramatic increase of their intrinsic acidity. Hence, whereas 1H-tetrazole can be considered as a typical N base in the gas phase, the complex 1H-tetrazole-BeCl2 is predicted to be, through the use of high-level G4 ab initio calculations, a nitrogen acid stronger than perchloric acid. This acidity enhancement is due to a more favorable stabilization of the deprotonated species after the beryllium bond is formed, because the deprotonated anion is a much better electron donor than the neutral species. Consequently, this is a general phenomenon that should be observed for any Lewis base, including those in which the basic site is a hydroxy group, an amino group, a carbonyl group, an aromatic N atom, a second-row atom, or the π system of unsaturated hydrocarbons. The consequence is that typical bases like aniline or formamide lead to BeX2 complexes that are stronger acids than phosphoric or chloric acids. Similarly, water, methanol, and SH2 become stronger acids than sulfuric acid, pyridine becomes a C acid almost as strong as acetic acid, and unsaturated hydrocarbons such as ethylene and acetylene become acids as strong as nitric and sulfuric acids, respectively. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A two-dimensional layered Cd(II) coordination polymer with a three-dimensional supramolecular architecture incorporating mixed multidentate N- and O-donor ligands.

PubMed

Huang, Qiu-Ying; Su, Ming-Yang; Meng, Xiang-Ru

2015-06-01

The combination of N-heterocyclic and multicarboxylate ligands is a good choice for the construction of metal-organic frameworks. In the title coordination polymer, poly[bis{μ2-1-[(1H-benzimidazol-2-yl)methyl]-1H-tetrazole-κ(2)N(3):N(4)}(μ4-butanedioato-κ(4)O(1):O(1'):O(4):O(4'))(μ2-butanedioato-κ(2)O(1):O(4))dicadmium], [Cd(C4H4O4)(C9H8N6)]n, each Cd(II) ion exhibits an irregular octahedral CdO4N2 coordination geometry and is coordinated by four O atoms from three carboxylate groups of three succinate (butanedioate) ligands and two N atoms from two 1-[(1H-benzimidazol-2-yl)methyl]-1H-tetrazole (bimt) ligands. Cd(II) ions are connected by two kinds of crystallographically independent succinate ligands to generate a two-dimensional layered structure with bimt ligands located on each side of the layer. Adjacent layers are further connected by hydrogen bonding, leading to a three-dimensional supramolecular architecture in the solid state. Thermogravimetric analysis of the title polymer shows that it is stable up to 529 K and then loses weight from 529 to 918 K, corresponding to the decomposition of the bimt ligands and succinate groups. The polymer exhibits a strong fluorescence emission in the solid state at room temperature.

Effects of mutations on the insoluble glucan synthesized by Leuconostoc mesenteroides NRRL B-1118 glucansucrase

USDA-ARS?s Scientific Manuscript database

Twelve different amino acids were each substituted for Threonine-654 in a cloned glucansucrase from Leuconostoc mesenteroides NRRL B-1118 (DSR-I). The native enzyme produces a water-insoluble glucan containing approximately 44 mol% 1,3-disubstituted a-D-glucopyranosyl units and 29 mol% 1,6-disubstit...

Prodrug and covalent linker strategies for the solubilization of dual-action antioxidants/iron chelators.

PubMed

Bebbington, David; Dawson, Claire E; Gaur, Suneel; Spencer, John

2002-11-18

Water soluble prodrugs of hybrid free radical scavenger/iron chelating molecules, based on 3,5-disubstituted-4-hydroxyphenyl derivatives and 3-hydroxy-2-methyl-4(1H)-pyridinone (deferiprone), have been prepared. Related hybrid molecules containing a covalent poly(ethylene)glycol or an amine linker were also synthesized.

40 CFR 721.4100 - Tris(disubstituted alkyl) het-er-o-cy-cle.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for... substance is present in a plastic, an elastomer, a rubber matrix, or in a solution. (iii) Industrial... substance imported in a plastic, an elastomer, a rubber matrix, or in a solution, such that inhalation is...

40 CFR 721.4100 - Tris(disubstituted alkyl) het-er-o-cy-cle.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for... substance is present in a plastic, an elastomer, a rubber matrix, or in a solution. (iii) Industrial... substance imported in a plastic, an elastomer, a rubber matrix, or in a solution, such that inhalation is...

IMMUNE FUNCTION IS NOT IMPAIRED IN SPRAGUE-DAWLEY RATS EXPOSED TO DIMETHYLTIN DICHLORIDE (DMTC) DURING DEVELOPMENT OR ADULTHOOD

EPA Science Inventory

Abstract

Organotins are used commercially as pesticides, antifouling agents and stabilizers for polyvinyl chloride (PVC) pipe. Mono- and di-substituted butyltins, used in PVC pipe production, are of concern to the U.S. EPA because they leach from supply pipes into drinkin...

40 CFR 721.7220 - Polymer of substituted phenol, formaldehyde, epichlorohydrin, and disubstituted benzene.

Code of Federal Regulations, 2012 CFR

2012-07-01

... specified in § 721.90(c)(2)(v), or diatomaceous earth filtration. (b) Specific requirements. The provisions... subject to reporting. (1) The chemical substance identified generically as polymer of substituted phenol... section for the significant new uses described in paragraph (a)(2) of this section. (2) The significant...

40 CFR 721.7220 - Polymer of substituted phenol, formaldehyde, epichlorohydrin, and disubstituted benzene.

Code of Federal Regulations, 2011 CFR

2011-07-01

... specified in § 721.90(c)(2)(v), or diatomaceous earth filtration. (b) Specific requirements. The provisions... subject to reporting. (1) The chemical substance identified generically as polymer of substituted phenol... section for the significant new uses described in paragraph (a)(2) of this section. (2) The significant...

40 CFR 721.7220 - Polymer of substituted phenol, formaldehyde, epichlorohydrin, and disubstituted benzene.

Code of Federal Regulations, 2014 CFR

2014-07-01

... specified in § 721.90(c)(2)(v), or diatomaceous earth filtration. (b) Specific requirements. The provisions... subject to reporting. (1) The chemical substance identified generically as polymer of substituted phenol... section for the significant new uses described in paragraph (a)(2) of this section. (2) The significant...

40 CFR 721.7220 - Polymer of substituted phenol, formaldehyde, epichlorohydrin, and disubstituted benzene.

Code of Federal Regulations, 2013 CFR

2013-07-01

... specified in § 721.90(c)(2)(v), or diatomaceous earth filtration. (b) Specific requirements. The provisions... subject to reporting. (1) The chemical substance identified generically as polymer of substituted phenol... section for the significant new uses described in paragraph (a)(2) of this section. (2) The significant...

40 CFR 721.305 - Di-substituted acetophenone (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

... (PMN P-97-93) is subject to reporting under this section for the significant new uses described in...): This substance is expected to be dermally absorbed and may cause effects to the liver, kidney, adrenal... in § 721.125 (a), (b), (c), (d), (e), (f), (g), (h), and (i) are applicable to manufacturers...

40 CFR 721.8153 - Di-substituted propanedione (generic).

Code of Federal Regulations, 2013 CFR

2013-07-01

... (PMN P-97-94) is subject to reporting under this section for the significant new uses described in...): This substance is expected to be dermally absorbed and may cause effects to the liver, kidney, adrenal... in § 721.125 (a), (b), (c), (d), (e), (f), (g), (h), and (i) are applicable to manufacturers...

40 CFR 721.305 - Di-substituted acetophenone (generic).

Code of Federal Regulations, 2011 CFR

2011-07-01

... (PMN P-97-93) is subject to reporting under this section for the significant new uses described in...): This substance is expected to be dermally absorbed and may cause effects to the liver, kidney, adrenal... in § 721.125 (a), (b), (c), (d), (e), (f), (g), (h), and (i) are applicable to manufacturers...

40 CFR 721.8153 - Di-substituted propanedione (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

... (PMN P-97-94) is subject to reporting under this section for the significant new uses described in...): This substance is expected to be dermally absorbed and may cause effects to the liver, kidney, adrenal... in § 721.125 (a), (b), (c), (d), (e), (f), (g), (h), and (i) are applicable to manufacturers...

40 CFR 721.8153 - Di-substituted propanedione (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

... (PMN P-97-94) is subject to reporting under this section for the significant new uses described in...): This substance is expected to be dermally absorbed and may cause effects to the liver, kidney, adrenal... in § 721.125 (a), (b), (c), (d), (e), (f), (g), (h), and (i) are applicable to manufacturers...

40 CFR 721.8153 - Di-substituted propanedione (generic).

Code of Federal Regulations, 2012 CFR

2012-07-01

... (PMN P-97-94) is subject to reporting under this section for the significant new uses described in...): This substance is expected to be dermally absorbed and may cause effects to the liver, kidney, adrenal... in § 721.125 (a), (b), (c), (d), (e), (f), (g), (h), and (i) are applicable to manufacturers...

40 CFR 721.305 - Di-substituted acetophenone (generic).

Code of Federal Regulations, 2013 CFR

2013-07-01

... (PMN P-97-93) is subject to reporting under this section for the significant new uses described in...): This substance is expected to be dermally absorbed and may cause effects to the liver, kidney, adrenal... in § 721.125 (a), (b), (c), (d), (e), (f), (g), (h), and (i) are applicable to manufacturers...

40 CFR 721.305 - Di-substituted acetophenone (generic).

Code of Federal Regulations, 2012 CFR

2012-07-01

... (PMN P-97-93) is subject to reporting under this section for the significant new uses described in...): This substance is expected to be dermally absorbed and may cause effects to the liver, kidney, adrenal... in § 721.125 (a), (b), (c), (d), (e), (f), (g), (h), and (i) are applicable to manufacturers...

40 CFR 721.8153 - Di-substituted propanedione (generic).

Code of Federal Regulations, 2011 CFR

2011-07-01

... (PMN P-97-94) is subject to reporting under this section for the significant new uses described in...): This substance is expected to be dermally absorbed and may cause effects to the liver, kidney, adrenal... in § 721.125 (a), (b), (c), (d), (e), (f), (g), (h), and (i) are applicable to manufacturers...

40 CFR 721.305 - Di-substituted acetophenone (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

... (PMN P-97-93) is subject to reporting under this section for the significant new uses described in...): This substance is expected to be dermally absorbed and may cause effects to the liver, kidney, adrenal... in § 721.125 (a), (b), (c), (d), (e), (f), (g), (h), and (i) are applicable to manufacturers...

Catalytic asymmetric synthesis of 2,2-disubstituted oxetanes from ketones by using a one-pot sequential addition of sulfur ylide.

PubMed

Sone, Toshihiko; Lu, Gang; Matsunaga, Shigeki; Shibasaki, Masakatsu

2009-01-01

Better the second time around: The title compounds were synthesized by using a one-pot double methylene transfer catalyzed by a heterobimetallic La/Li complex. Chiral amplification in the second step was the key to obtaining oxetanes in high enantiomeric excess (see scheme).

Structure-Activity Relationships of 1,2-Disubstituted Benzimidazoles: Selective Inhibition of Heme Oxygenase-2 Activity.

PubMed

Kong, Xianqi; Vukomanovic, Dragic; Nakatsu, Kanji; Szarek, Walter A

2015-08-01

Devising ways to up- or down-regulate heme oxygenase activity is attracting much interest as a strategy for the treatment of a variety of disorders. With a view of obtaining compounds that exhibit high potency and selectivity as inhibitors of the heme oxygenase-2 (HO-2) isozyme (constitutive) relative to the heme oxygenase-1 (HO-1) isozyme (inducible), several 1,2-disubstituted 1H-benzimidazoles were designed and synthesized. Specifically, analogues were synthesized in which the C2 substituent was the following: (1H-imidazol-1-yl)methyl, (N-morpholinyl)methyl, cyclopentylmethyl, cyclohexylmethyl, or (norborn-2-yl)methyl. Compounds with the cyclic system in the C2 substituent being a carbocyclic ring, especially cyclohexyl or norborn-2-yl, and the N1 substituent being a ring-substituted benzyl group, especially 4-chlorobenzyl or 4-bromobenzyl, best exhibited the target criteria of high potency and selectivity toward inhibition of HO-2. The new candidates should be useful pharmacological tools and may have therapeutic applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Azaphenalene phthalocyanines: phthalocyanine analogues with six-membered-ring units instead of five-membered-ring units.

PubMed

Shimizu, Soji; Zhu, Hua; Kobayashi, Nagao

2010-09-24

Mixed-condensation reaction of 1,8-naphthalenedicarbonitrile and a 4,5-disubstituted phthalonitrile provided a series of phthalocyanine (Pc) analogues with azaphenalene (AP) moieties in place of the isoindole moieties. Monosubstituted species, APPc, and the two structural isomers of disubstituted species, adj-AP(2)Pc and opp-AP(2)Pc, were successfully isolated by gel-permeation chromatography on HPLC apparatus. Their structures were elucidated by (1)H NMR spectroscopy and X-ray crystallographic analysis. Replacement of the isoindole moieties with azaphenalene moieties created six-membered-ring units in the core and caused distortion of the molecular structures. The Q-band absorption shifted to the red upon an increase in the number of azaphenalene units; the shape of the absorption spectra depended on the molecular symmetries. APPc and opp-AP(2)Pc showed a large splitting of the Q band, whereas adj-AP(2)Pc exhibited a single broad Q band. These changes in the absorption spectra, as well as the unique electronic structures, are discussed in detail, based on magnetic circular dichroism spectra, electrochemical measurements, and density functional theory calculations.

Photo-inducible cytotoxic and clastogenic activities of 3,6-di-substituted acridines obtained by acylation of proflavine.

PubMed

Benchabane, Yohann; Di Giorgio, Carole; Boyer, Gérard; Sabatier, Anne-Sophie; Allegro, Diane; Peyrot, Vincent; De Méo, Michel

2009-06-01

The cytotoxicity and photo-enhanced cytotoxicity of a series of 18 3,6-di-substituted acridines were evaluated on both tumour CHO cells and human normal keratinocytes, and compared to their corresponding clastogenicity as assessed by the micronucleus assay. Compounds 2f tert-butyl N-[(6-tert-butoxycarbonylamino)acridin-3-yl]carbamate and 2d N-[6-(pivalamino)acridin-3-yl]pivalamide displayed a specific cytotoxicity on CHO cells. These results suggested that the two derivatives could be considered as interesting candidates for anticancer chemotherapy and hypothesized that the presence of 1,1-dimethylethyl substituents was responsible for a strong nonclastogenic cytotoxicity. Compounds 2b and 2c, on the contrary, displayed a strong clastogenicity. They indicated that the presence of nonbranched aliphatic chains on positions 3 and 6 of the acridine rings tended to induce a significant clastogenic effect. Finally, they established that most of the acridine compounds could be photo-activated by UVA-visible rays and focussed on the significant role of light irradiation on their biological properties.

A convenient synthesis of 6-amino-1-beta-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-4-one and related 4,6-disubstituted pyrazolopyrimidine nucleosides.

PubMed Central

Cottam, H B; Revankar, G R; Robins, R K

1983-01-01

The glycosylation of 4,6-dichloropyrazolo[3,4-d]pyrimidine and 4-chloro-6-methylthiopyrazolo[3,4-d]pyrimidine via the corresponding trimethylsilyl intermediate and tetra-O-acetyl-beta-D-ribofuranose in the presence of trimethylsilyl triflate as a catalyst, gave selective glycosylation at N1 as the only nucleoside product. The intermediates 4,6-dichloro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)pyrazolo [3,4-d]pyrimidine 7 and 4-chloro-6-methylthio-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)pyrazolo [3,4-d]pyrimidine 13 gave new and convenient synthetic routes to the inosine analog 1, the guanosine analog 2, the adenosine analog 3, and the isoguanosine analog 16. Glycosylation of the trimethylsilyl derivative of 6-chloropyrazolo[3,4-d]pyrimidine-4-one unexpectedly gave the N2-glycosyl isomer 20 as the major product. A number of new 4,6-disubstituted pyrazolo[3,4-d]pyrimidine nucleosides were prepared from these glycosyl intermediates. PMID:6835838

An efficient one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles at room temperature by green synthesized Cu NPs using Otostegia persica leaf extract.

PubMed

Nasrollahzadeh, Mahmoud; Sajadi, S Mohammad; Mirzaei, Yousef

2016-04-15

In this study, copper nanoparticles (Cu NPs) were synthesized using a rapid, single step and completely green biosynthetic method by reduction of CuCl2 · 2H2O solution with aqueous extract of leaves of Otostegia persica containing flavonoid and other phenolics as a main factor which acts as reducing agent and efficient stabilizer. UV-vis spectra gave surface plasmon resonance (SPR) at 560 nm. The Cu NPs were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). A possible synthesis mechanism of Cu NPs was presented. In addition, we investigated the catalytic activity of Cu NPs for the one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles under mild reaction conditions with good to excellent yields. The catalyst could be easily recovered by centrifugation and reused at least five recycles with no significant decreases in the yields. Copyright © 2016 Elsevier Inc. All rights reserved.

Consistent assignment of the vibrations of symmetric and asymmetric para-disubstituted benzene molecules

NASA Astrophysics Data System (ADS)

Andrejeva, Anna; Gardner, Adrian M.; Tuttle, William D.; Wright, Timothy G.

2016-03-01

We give a description of the phenyl-ring-localized vibrational modes of the ground states of the para-disubstituted benzene molecules including both symmetric and asymmetric cases. In line with others, we quickly conclude that the use of Wilson mode labels is misleading and ambiguous; we conclude the same regarding the related ones of Varsányi. Instead we label the modes consistently based upon the Mulliken (Herzberg) method for the modes of para-difluorobenzene (pDFB). Since we wish the labelling scheme to cover both symmetrically- and asymmetrically-substituted molecules, we apply the Mulliken labelling under C2v symmetry. By studying the variation of the vibrational wavenumbers with mass of the substituent, we are able to identify the corresponding modes across a wide range of molecules and hence provide consistent assignments. Particularly interesting are pairs of vibrations that evolve from in- and out-of-phase motions in pDFB to more localized modes in asymmetric molecules. We consider the para isomers of the following: the symmetric dihalobenzenes, xylene, hydroquinone, the asymmetric dihalobenzenes, halotoluenes, halophenols and cresol.

4-hydroxyphenylacetic acid derivatives of inositol from dandelion (Taraxacum officinale) root characterised using LC-SPE-NMR and LC-MS techniques.

PubMed

Kenny, O; Smyth, T J; Hewage, C M; Brunton, N P; McLoughlin, P

2014-02-01

The combination of hyphenated techniques, LC-SPE-NMR and LC-MS, to isolate and identify minor isomeric compounds from an ethyl acetate fraction of Taraxacum officinale root was employed in this study. Two distinct fractions of 4-hydroxyphenylacetic acid derivatives of inositol were isolated and characterised by spectroscopic methods. The (1)H NMR spectra and MS data revealed two groups of compounds, one of which were derivatives of the di-4-hydroxyphenylacetic acid derivative of the inositol compound tetrahydroxy-5-[2-(4-hydroxyphenyl)acetyl] oxycyclohexyl-2-(4-hydroxyphenyl) acetate, while the other group consisted of similar tri-substituted inositol derivatives. For both fractions the derivatives of inositols vary in the number of 4-hydroxyphenylacetic acid groups present and their position and geometry on the inositol ring. In total, three di-substituted and three tri-substituted 4-hydroxyphenylacetic acid inositol derivates were identified for the first time along with a further two previously reported di-substituted inositol derivatives. Copyright © 2013 Elsevier Ltd. All rights reserved.

In Vitro Activity of Neomycin, Streptomycin, Paromomycin and Apramycin against Carbapenem-Resistant Enterobacteriaceae Clinical Strains

PubMed Central

Hu, Ya; Liu, Lu; Zhang, Xiaoxia; Feng, Yu; Zong, Zhiyong

2017-01-01

We determined the in vitro susceptibility of four aminoglycosides, which are not of the 4,6-disubstituted deoxystreptamine (DOS) subclass against a collection of carbapenem-resistant Enterobacteriaceae (CRE). CRE clinical strains (n = 134) were collected from multiple hospitals in China and carried blaNDM (blaNDM−1, blaNDM−5 or blaNDM−7; n = 66), blaKPC−2 (n = 62) or blaIMP−4 (n = 7; including one carrying blaNDM−1 and blaIMP−4). MICs of neomycin, paromomycin, streptomycin and apramycin as well as three 4,6-disubstituted DOS aminoglycosides (amikacin, gentamicin and tobramycin) were determined using the broth microdilution with breakpoints defined by the Clinical Laboratory Standards Institute (for amikacin, gentamicin and tobramycin), US Food and Drug Administration (streptomycin), the National Antimicrobial Resistance Monitoring System (apramycin) or la Société Française de Microbiologie (neomycin and paromomycin). Apramycin-resistant strains were subjected to whole genome sequencing using Illumina X10 platform. Among CRE strains, 65.7, 64.9, 79.1, and 95.5% were susceptible to neomycin (MIC50/MIC90, 8/256 μg/ml), paromomycin (4/>256 μg/ml), streptomycin (16/256 μg/ml) and apramycin (4/8 μg/ml), respectively, while only 55.2, 28.4, and 35.1% were susceptible to amikacin (32/>256 μg/ml), gentamicin (128/>256 μg/ml) and tobramycin (64/>256 μg/ml), respectively. Six CRE strains including five Escherichia coli of different sequence types and one Klebsiella pneumoniae were resistant to apramycin and the apramycin-resistant gene aac(3)-IVa was detected in all of these strains. In conclusion, neomycin, paromomycin, streptomycin and apramycin retain activity against most CRE strains. Although none of these non-4,6-disubstituted DOS aminoglycosides are suitable for intravenous use in human at present, these agents warrant further investigations to be used against CRE infections. PMID:29250040

In Vitro Activity of Neomycin, Streptomycin, Paromomycin and Apramycin against Carbapenem-Resistant Enterobacteriaceae Clinical Strains.

PubMed

Hu, Ya; Liu, Lu; Zhang, Xiaoxia; Feng, Yu; Zong, Zhiyong

2017-01-01

We determined the in vitro susceptibility of four aminoglycosides, which are not of the 4,6-disubstituted deoxystreptamine (DOS) subclass against a collection of carbapenem-resistant Enterobacteriaceae (CRE). CRE clinical strains ( n = 134) were collected from multiple hospitals in China and carried bla NDM ( bla NDM-1 , bla NDM-5 or bla NDM-7 ; n = 66), bla KPC-2 ( n = 62) or bla IMP-4 ( n = 7; including one carrying bla NDM-1 and bla IMP-4 ). MICs of neomycin, paromomycin, streptomycin and apramycin as well as three 4,6-disubstituted DOS aminoglycosides (amikacin, gentamicin and tobramycin) were determined using the broth microdilution with breakpoints defined by the Clinical Laboratory Standards Institute (for amikacin, gentamicin and tobramycin), US Food and Drug Administration (streptomycin), the National Antimicrobial Resistance Monitoring System (apramycin) or la Société Française de Microbiologie (neomycin and paromomycin). Apramycin-resistant strains were subjected to whole genome sequencing using Illumina X10 platform. Among CRE strains, 65.7, 64.9, 79.1, and 95.5% were susceptible to neomycin (MIC 50 /MIC 90 , 8/256 μg/ml), paromomycin (4/>256 μg/ml), streptomycin (16/256 μg/ml) and apramycin (4/8 μg/ml), respectively, while only 55.2, 28.4, and 35.1% were susceptible to amikacin (32/>256 μg/ml), gentamicin (128/>256 μg/ml) and tobramycin (64/>256 μg/ml), respectively. Six CRE strains including five Escherichia coli of different sequence types and one Klebsiella pneumoniae were resistant to apramycin and the apramycin-resistant gene aac(3)-IVa was detected in all of these strains. In conclusion, neomycin, paromomycin, streptomycin and apramycin retain activity against most CRE strains. Although none of these non-4,6-disubstituted DOS aminoglycosides are suitable for intravenous use in human at present, these agents warrant further investigations to be used against CRE infections.

Consistent assignment of the vibrations of symmetric and asymmetric ortho-disubstituted benzenes

NASA Astrophysics Data System (ADS)

Tuttle, William D.; Gardner, Adrian M.; Andrejeva, Anna; Kemp, David J.; Wakefield, Jonathan C. A.; Wright, Timothy G.

2018-02-01

The form of molecular vibrations, and changes in these, give valuable insights into geometric and electronic structure upon electronic excitation or ionization, and within families of molecules. Here, we give a description of the phenyl-ring-localized vibrational modes of the ground (S0) electronic states of a wide range of ortho-disubstituted benzene molecules including both symmetrically- and asymmetrically-substituted cases. We conclude that the use of the commonly-used Wilson or Varsányi mode labels, which are based on the vibrational motions of benzene itself, is misleading and ambiguous. In addition, we also find the use of the Mi labels for monosubstituted benzenes [A.M. Gardner, T.G. Wright. J. Chem. Phys. 135 (2011) 114305], or the recently-suggested labels for para-disubstituted benzenes [A. Andrejeva, A.M. Gardner, W.D. Tuttle, T.G. Wright, J. Molec. Spectrosc. 321, 28 (2016)] are not appropriate. Instead, we label the modes consistently based upon the Mulliken (Herzberg) method for the modes of ortho-difluorobenzene (pDFB) under Cs symmetry, since we wish the labelling scheme to cover both symmetrically- and asymmetrically-substituted molecules. By studying the vibrational wavenumbers from the same force field while varying the mass of the substituent, we are able to identify the corresponding modes across a wide range of molecules and hence provide consistent assignments. We assign the vibrations of the following sets of molecules: the symmetric o-dihalobenzenes, o-xylene and catechol (o-dihydroxybenzene); and the asymmetric o-dihalobenzenes, o-halotoluenes, o-halophenols and o-cresol. In the symmetrically-substituted species, we find a pair of in-phase and out-of-phase carbon-substituent stretches, and this motion persists in asymmetrically-substituted molecules for heavier substituents. When at least one of the substituents is light, then we find that these evolve into localized carbon-substituent stretches.

Isolation of a Moderately Stable but Sensitive Zwitterionic Diazonium Tetrazolyl-1,2,3-triazolate.

PubMed

Klapötke, Thomas M; Krumm, Burkhard; Pflüger, Carolin

2016-07-15

An unexpected formation of a diazonium compound was observed by nitration of an amino substituted triazolyl tetrazole with mixed acid. The crystal structure determination revealed a zwitterionic diazonium tetrazolyl-1,2,3-triazolate, whose constitution was supported by NMR and vibrational spectroscopic analysis. The thermal stability and sensitivity toward impact and friction were determined. In contrast, diazotriazoles are rather unstable and are mainly handled in solution and/or low temperatures, which is not the case for this diazonium tetrazolyl-1,2,3-triazolate, being stable at ambient temperature.

An Atom-Economic Synthesis of Nitrogen Heterocycles from Alkynes

PubMed Central

Trost, Barry M.; Lumb, Jean-Philip; Azzarelli, Joseph M.

2011-01-01

A robust route to 2,4-disubstituted pyrrole heterocycles relying upon a cascade reaction is reported. The reaction benefits from operational simplicity: it is air and moisture tolerant and is performed at ambient temperature. Control over the reaction conditions provides ready access to isopyrroles, 2,3,4- trisubstituted pyrroles and 3- substituted pyrollidin-2-ones. PMID:21175138

Synthesis and Hydrogenation of Disubstituted Chalcones: A Guided-Inquiry Organic Chemistry Project

ERIC Educational Resources Information Center

Mohrig, Jerry R.; Hammond, Christina Noring; Schatz, Paul F.; Davidson, Tammy A.

2009-01-01

Guided-inquiry experiments offer the same opportunities to participate in the process of science as classical organic qualitative analysis used to do. This three-week guided-inquiry project involves an aldol-dehydration synthesis of a chalcone chosen from a set of nine, followed by a catalytic transfer hydrogenation reaction using ammonium formate…

DEVELOPMENTAL EXPOSURE TO 1.0 OR 2.5 MG/KG DIBUTYLTIN DICHLORIDE DOES NOT IMPAIR IMMUNE FUNCTION IN SPRAGUE-DAWLEY RATS

EPA Science Inventory

Organotins are used commercially as pesticides, antifouling agents and stabilizers for polyvinyl chloride (PVC) pipe. Mono- and di-substituted methyl and butyltins, used in PVC pipe production, are of concern to the U.S. EPA as they leach from supply pipes into drinking water an...

Defense.gov Special Report: Travels with Winnefeld: USO Tour

Science.gov Websites

: USO April 2012 Top Stories USO Tour Brings Ramstein Troops, Families Together Service members and USO celebrities paid a surprise visit to wounded warriors at an aeromedical staging facility on Ramstein Air Base in Germany. Story USO Spring Tour Entertains Troops in Afghanistan Nearly 400 excited

Three new energetic complexes with N,N-bis(1H-tetrazole-5-yl)-amine as high energy density materials: syntheses, structures, characterization and effects on the thermal decomposition of RDX.

PubMed

Yang, Qi; Song, Xiaxia; Zhang, Wendou; Hou, Lei; Gong, Qibing; Xie, Gang; Wei, Qing; Chen, Sanping; Gao, Shengli

2017-02-21

Three new energetic complexes, [Pb(bta)(H 2 O)] n (1), [PbCu(bta) 2 (H 2 O) 5 ]·2H 2 O (2) and PbCu(bta) 2 (3) (H 2 bta = N,N-bis(1H-tetrazole-5-yl)-amine), have been synthesized and characterised. In particular, 3 was readily synthesized by dehydration of 2 at 190 °C. Single crystal X-ray diffraction revealed that 1 has a 3D framework structure and 2 presents a 3D supermolecular architecture. Thermoanalyses demonstrated that the main frames of 1 and 2 have good thermostabilities up to 314 °C for 1 and 231 °C for 2. Non-isothermal kinetic and thermodynamic parameters of exothermic decomposition processes of 1 and 2 were obtained by Kissinger's and Ozawa's methods. Based on the constant-volume combustion energies measured by a precise rotating-bomb calorimeter, the standard molar enthalpies of formation of 1 and 2 were determined. The calculation of the detonation properties of 1 and 2 and the impact sensitivity tests of 1, 2 and 3 were carried out. In addition, 1, 2 and 3 were explored as combustion promoters to accelerate the thermal decompositions of RDX (1,3,5-trinitro-1,3,5-triazine) by differential scanning calorimetry. Experimental results showed that 1, 2 and 3 can be used as HEDMs in the field of combustion promoters and insensitive 2 can be regarded as a safer form for mass storage and transportation than sensitive 3.

Synthesis and characterization of novel Cu(II) complex coated Fe3O4@SiO2 nanoparticles for catalytic performance

NASA Astrophysics Data System (ADS)

Nasrollahzadeh, Mahmoud; Sajjadi, Mohaddeseh; Khonakdar, Hossein Ali

2018-06-01

In this study, a convenient method for the synthesis of arylaminotetrazoles has been developed using a copper (II)-aminotetrazole complex immobilized on silica-coated Fe3O4 (Fe3O4@SiO2) nanoparticles (Fe3O4@SiO2-aminotet-Cu(II)) as a novel and efficient magnetically catalyst. The constructed superparamagnetic core-shell nanoparticles were successfully prepared, as proven using different spectroscopic techniques such as fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), transmission electron microscope (TEM), field emission scanning electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDS), thermogravimetry and differential thermogravimetry (TG-DTG) and vibrating sample magnetometer (VSM) analysis. The applicability of Fe3O4@SiO2-aminotet-Cu(II) magnetic catalyst allows the efficient synthesis of a variety of arylaminotetrazoles from the reaction between various arylcyanamides with sodium azide in high yields. The effect of catalyst loading was investigated. In addition, the reaction mechanism for the synthesis of arylaminotetrazoles was reasonably proposed. Results show that the 1-aryl-5-amino-1H-tetrazole (B isomer) and 5-arylamino-1H-tetrazole (A isomer) can be obtained from the arylcyanamides carrying electron-donating and electron-withdrawing substituents, respectively. This procedure offers a simple methodology, relatively short reaction times, easy work-up, high yields of the products and a cleaner reaction with elimination of hydrazoic acid (HN3). Moreover, catalyst can be conveniently recovered through the use of external magnet and reused for at least 6 times without any significant loss of its activity.

Mechanism of permeability-enhancing effect of EDTA and boric acid on the corneal penetration of 4-[1-hydroxy-1-methylethyl]-2-propyl-1-[4-[2-[tetrazole-5-yl]phenyl]phenyl] methylimidazole-5-carboxylic acid monohydrate (CS-088).

PubMed

Kikuchi, Takayuki; Suzuki, Masahiko; Kusai, Akira; Iseki, Ken; Sasaki, Hitoshi; Nakashima, Kenichiro

2005-08-11

This study was conducted to clarify the penetration properties of 4-[1-hydroxy-1-methylethyl]-2-propyl-1-[4-[2-[tetrazole-5-yl]phenyl]phenyl]methylimidazole-5-carboxylic acid monohydrate (CS-088), an ophthalmic agent, and the mechanism of the permeability-enhancing effect of EDTA and boric acid (EDTA/boric acid) on the corneal penetration of CS-088. In the absence of additives, corneal permeability decreased with increasing concentration of CS-088 as CS-088 monomers self-associate to form dimers. Presence of EDTA/boric acid caused no significant changes in the physicochemical properties of CS-088, the apparent partition coefficient or the mean particle size of CS-088. EDTA/boric acid induced only a slight change in the zeta potential of liposomes used as a model of the biological membrane. On the other hand, EDTA/boric acid significantly increased membrane fluidity of liposomes, whereas other buffering agents tested did not. This effect was synergistic and concentration-dependent for both EDTA and boric acid as was observed in in vitro corneal penetration of CS-088. In accordance with the result, the rate of CS-088 permeation into the liposomes significantly increased by the addition of EDTA/boric acid. Therefore, it was demonstrated that EDTA/boric acid promotes corneal penetration of CS-088 through the transcellular pathway by increasing membrane fluidity. Conversely, other buffering agents decreased corneal permeability of CS-088 by inducing further self-association of CS-088 aggregates.

Comparative theoretical studies of differently bridged nitramino-substituted ditetrazole 2-N-oxides with high detonation performance and an oxygen balance of around zero.

PubMed

Wu, Qiong; Kou, Bo; Hang, Zusheng; Zhu, Weihua

2017-06-01

In this work, six (A-F) nitramino (-NHNO 2 )-substituted ditetrazole 2-N-oxides with different bridging groups (-CH 2 -, -CH 2 -CH 2 -, -NH-, -N=N-, and -NH-NH-) were designed. The six compounds were based on the parent compound tetrazole 2-N-oxide, which possesses a high oxygen balance and high density. The structure, heat of formation, density, detonation properties (detonation velocity D and detonation pressure P), and the sensitivity of each compound was investigated systematically via density functional theory, by studying the electrostatic potential, and using molecular mechanics. The results showed that compounds A-F all have outstanding energetic properties (D: 9.1-10.0 km/s; P: 38.0-46.7 GPa) and acceptable sensitivities (h 50 : 28-37 cm). The bridging group present was found to greatly affect the detonation performance of each ditetrazole 2-N-oxide, and the compound with the -NH-NH- bridging group yielded the best results. Indeed, this compound (F) was calculated to have comparable sensitivity to the famous and widely used high explosive 1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX), but with values of D and P that were about 8.7% and 19.4% higher than those for HMX, respectively. The present study shows that tetrazole 2-N-oxide is a useful parent compound which could potentially be used in the design of new and improved high-energy compounds to replace existing energetic compounds such as HMX.

Synthesis and antinociceptive evaluation of bioisosteres and hybrids of naproxen, ibuprofen and paracetamol.

PubMed

González-Trujano, María Eva; Uribe-Figueroa, Gerardo; Hidalgo-Figueroa, Sergio; Martínez, Ana Laura; Déciga-Campos, Myrna; Navarrete-Vazquez, Gabriel

2018-05-01

The aim of this work was to design, synthesize and characterize the potential anti-nociceptive and anti-inflammatory activities of a new series of bioisosteres and hybrids from known non-steroidal anti-inflammatory drugs (NSAIDs). The compounds 4-(acetylamino)phenyl (2S)-2-(6-methoxy-2-naphthyl)propanoate (GUF-1) and 4-(acetylamino)phenyl 2-(R,S)-(4-isobutylphenyl)propanoate (GUF-2) were synthesized as hybrids (also known as heterodimers); whereas those named 2-(R,S)-(4-isobutylphenyl)-N-1H-tetrazol-5-ylpropanamide (GUF-3), (2S)-2-(6-methoxy-2-naphthyl)-N-1H-tetrazol-5-ylpropanamide (GUF-4), [2-(R,S)-N-hydroxy-2-[4-(2-methylpropyl)phenyl]propanamide] (GUF-5), and (2S)-N-hydroxy-2-(6-methoxy-2-naphthyl)propanamide (GUF-6) were synthesized as bioisosteres of the NSAIDs paracetamol, ibuprofen, and naproxen, respectively. All these compounds were characterized by spectroscopic and spectrometric analysis. Antinociceptive activity of GUF-1 to GUF-6 was evaluated using the formalin test in rats. Pharmacological responses of GUF-1, GUF-2 (hybrids), and GUF-5 (bioisostere) demonstrated significant antinociceptive effects; thus these compounds were assayed in an inflammation test like carrageenan-induced paw oedema in rats. Complete molecular docking of cyclooxygenase and the GUF-1 and GUF-2 hybrids showed high docking scores, compared to the reference drugs. Our data demonstrate that compounds GUF-1, GUF-2, and GUF-5 possesses antinociceptive and antiinflammatory activities resembling and improving those known for the traditional NSAIDs, paracetamol, naproxen and ibuprofen. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Palladium Hydride Promoted Stereoselective Isomerization of Unactivated Di(exo)methylenes to Endocyclic Dienes

PubMed Central

2015-01-01

The exomethylenes of 2,6-disubstituted bicyclo[3.3.1]nonan-9-ones 2 are readily isomerized over a palladium catalyst under an atmosphere of hydrogen to predominantly form the isomer 3 with C2 symmetry with very little formation of the analogous product with Cs symmetry. A hydrogen source is essential to effect the rearrangement. PMID:24720691

Concise, Stereocontrolled Synthesis of the Citrinadin B Core Architecture

PubMed Central

Guerrero, Carlos A.; Sorensen, Erik J.

2011-01-01

A concise, stereocontrolled synthesis of the citrinadin B core architecture from scalemic, readily available starting materials is disclosed. Highlights include ready access to both cyclic tryptophan tautomer and TRANS-2,6-disubstituted piperidine fragments, an efficient, stereoretentive mixed Claisen acylation for the coupling of these halves, and further diastereoselective carbonyl addition and oxidative rearrangement for assembly of the core. PMID:21894952

The synthesis of 5-substituted ring E analogs of methyllycaconitine via the Suzuki-Miyaura cross-coupling reaction.

PubMed

Huang, Junfeng; Orac, Crina M; McKay, Susan; McKay, Dennis B; Bergmeier, Stephen C

2008-04-01

Novel 3,5-disubstituted ring E analogs of methyllycaconitine were prepared and evaluated in nicotinic acetylcholine receptor binding assays. The desired analogs were prepared through the Suzuki-Miyaura cross-coupling reaction of methyl 5-bromo-nicotinate. The Suzuki-Miyaura cross-coupling reactions of pyridines with electron withdrawing substituents have not been extensively described previously.

Synthesis and fungicidal activity of novel 2,5-disubstituted-1,3,4- thiadiazole derivatives containing 5-phenyl-2-furan

NASA Astrophysics Data System (ADS)

Cui, Zi-Ning; Li, Ya-Sheng; Hu, De-Kun; Tian, Hao; Jiang, Jia-Zhen; Wang, Yuan; Yan, Xiao-Jing

2016-01-01

A series of 2,5-disubstituted-1,3,4-thiadiazoles were synthesized using Lawesson’s reagent by an efficient approach under microwave irradiation in good yields. Their structures were characterized by MS, IR, 1H NMR, 13C NMR, and elemental analysis. Their in vitro and in vivo fungicidal activities revealed that the title compounds exhibited considerable activity against five selected fungi, especially to Phytophthora infestans. In order to illustrate the mechanism of title compounds against P. infestans, scanning electron micrographs (SEM) and transmission electron micrographs (TEM) were applied. The morphological and ultrastructural studies demonstrated that compound I18 led to swelling of hyphae, thickening and proliferating multilayer cell walls, excessive septation and accumulation of dense bodies. The bioassay results indicated compound I18 might act on cell wall biosynthesis, and blocked the nutrition transportation and led to cells senescence and death. Meanwhile, compound I18 had broad fungicidal activity against other twenty different kinds of fungi. These results suggested that title compounds were eligible to be development candidates and compound I18 as a promising lead compound was worthy to be further discovery, especially against P. infestans.

A new class of nitrosoureas. 4. Synthesis and antitumor activity of disaccharide derivatives of 3,3-disubstituted 1-(2-chloroethyl)-1-nitrosoureas.

PubMed

Tsujihara, K; Ozeki, M; Morikawa, T; Kawamori, M; Akaike, Y; Arai, Y

1982-04-01

A series of 33 N-(2-chloroethyl)-N-nitrosocarbamoyl derivatives of N-substituted glycosylamines has been prepared and tested for antitumor activities. The compounds were obtained by reaction of glycosylamines with isocyanate, followed by nitrosation with N2O4. Structure-activity relationships of these trisubstituted nitrosoureas were investigated by varying the N-substituents and disaccharide groups and by comparing them with the corresponding disubstituted analogues. A large number of the nitrosoureas bearing a maltosyl group exhibited strong antitumor activities against leukemia L1210 and Ehrlich ascites carcinoma, and 60-day survivors against leukemia L1210 were found at the optimal dose for these derivatives. In contrast, the lactosyl and the melibiosyl derivatives were almost inactive. The most interesting compound in this series, the 3-isobutyl-3-maltosyl derivative (37), was tested against leukemia L1210 by single and multiple treatment. Its therapeutic ratio (96.3) obtained by multiple treatment is 3 times larger than that (31.5) obtained by single treatment, suggesting a possible clinical utility of 37 by multiple treatment. The favorable effect of a maltosyl moiety in this class of compounds is discussed.

Fused heterocyclic compounds bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 1: design, synthesis and biological evaluation of novel 5,7-disubstituted pyrazolo[1,5-a]pyrimidine derivatives.

PubMed

Tian, Ye; Du, Deping; Rai, Diwakar; Wang, Liu; Liu, Huiqing; Zhan, Peng; De Clercq, Erik; Pannecouque, Christophe; Liu, Xinyong

2014-04-01

In our continuous efforts to identify novel potent HIV-1 NNRTIs, a novel class of 5,7-disubstituted pyrazolo[1,5-a]pyrimidine derivatives were rationally designed, synthesized and evaluated for their anti-HIV activities in MT4 cell cultures. Biological results showed that most of the tested compounds displayed excellent activity against wild-type HIV-1 with a wide range of EC50 values from 5.98 to 0.07μM. Among the active compounds, 5a was found to be the most promising analogue with an EC50 of 0.07μM against wild-type HIV-1 and very high selectivity index (SI, 3999). Compound 5a was more effective than the reference drugs nevirapine (by 2-fold) and delavirdine (by 2-fold). In order to further confirm their binding target, an HIV-1 RT inhibitory assay was also performed. Furthermore, SAR analysis among the newly synthesized compounds was discussed and the binding mode of the active compound 5a was rationalized by molecular modeling studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of single bond-ion and single bond-diradical form on the stretching vibration of Cdbnd N bridging bond in 4,4‧-disubstituted benzylidene anilines

NASA Astrophysics Data System (ADS)

Cao, Chao-Tun; Bi, Yakun; Cao, Chenzhong

2016-06-01

Fifty-seven samples of model compounds, 4,4‧-disubstituted benzylidene anilines, p-X-ArCH = NAr-p-Y were synthesized. Their infrared absorption spectra were recorded, and the stretching vibration frequencies νCdbnd N of the Cdbnd N bridging bond were determined. New stretching vibration mode was proposed by means of the analysis of the factors affecting νCdbnd N, that is there are mainly three modes in the stretching vibration of Cdbnd N bond: (I) polar double bond form Cdbnd N, (II) single bond-ion form C+-N- and (III) single bond-diradical form Crad -Nrad . The contributions of the forms (I) and (II) to the change of νCdbnd N can be quantified by using Hammett substituent constant (including substituent cross-interaction effects between X and Y groups), whereas the contribution of the form (III) can be quantified by employing the excited-state substituent constant. The most contribution of these three forms is the form (III), the next is the form (II), whose contribution difference was discussed with the viewpoint of energy requirements in vibration with the form (III) and form (II).

Tautomerization and Dimerization of 6,13-Disubstituted Derivatives of Pentacene.

PubMed

Garcia-Borràs, Marc; Konishi, Akihito; Waterloo, Andreas; Liang, Yong; Cao, Yang; Hetzer, Constantin; Lehnherr, Dan; Hampel, Frank; Houk, Kendall N; Tykwinski, Rik R

2017-05-02

Two new 6,13-disubstituted pentacene derivatives, 1 c and 1 d, with alkyl and triisopropylsilylethynyl substitution have been synthesized and characterized experimentally and computationally. The alkyl substituted 1 c and 1 d represent the first 6-alkyl-substituted pentacene derivative where the fully aromatic species dominates over the corresponding tautomer. Indeed, no tautomerization product is found for either 1 c or 1 d upon heating or in the presence of catalytic amounts of acid. On the other hand, an unexpected dimer (3 c) is formed from 1 c. A plausible mechanism for this new dimerization process of the 6-methyl-substituted pentacene derivative 1 c is proposed, which involves first a bimolecular hydrogen atom transfer followed by an intramolecular [4+2] Diels-Alder cycloaddition. In the case of 6-butyl substitution, neither tautomerization nor dimerization is observed. Computations support the proposed 1 c dehydrodimerization pathway, explain why 1 d does not dimerize, and show the importance of the nature of the group at C-13 in controlling the relative stability of 6-alkyl-substituted pentacene tautomers. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design, synthesis and biological evaluation of novel HSP70 inhibitors: N, N'-disubstituted thiourea derivatives.

PubMed

Zeng, Yan-Qun; Cao, Rui-Yuan; Yang, Jian-Ling; Li, Xing-Zhou; Li, Song; Zhong, Wu

2016-08-25

As novel heat shock protein 70 (HSP70) inhibitors, N, N'-disubstituted thiourea derivatives were designed and synthesized based on the X-ray structure of the ATPase domain (nucleotide binding domain, NBD). An ATPase activity inhibition assay revealed that these compounds effectively inhibited HSP70 ATPase activity. The results revealed that the compounds 370/371/374/379/380//392/394/397/404/405 and 407 can inhibit the HSP70 ATPase turnover with high percentages of inhibition: 50.42, 38.46, 50.45, 44.12, 47.13, 50.50, 40.95, 65.36, 46.23, 35.78, and 58.37 in 200 μM, respectively. Significant synergies with lapatinib were observed for compound 379 and compound 405 in the BT474 breast cancer cell line. A structure-function analysis revealed that most of the thiourea derivatives exhibited cooperative action with lapatinib in the BT474 cancer cell line and the BT/Lap(R)1.0 lapatinib-resistant cell line. HSP70 inhibitors may be developed as synergetic drugs in drug-resistant cancer therapy. Copyright © 2016 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Binding of [alpha, alpha]-Disubstituted Amino Acids to Arginase Suggests New Avenues for Inhibitor Design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ilies, Monica; Di Costanzo, Luigi; Dowling, Daniel P.

Arginase is a binuclear manganese metalloenzyme that hydrolyzes L-arginine to form L-ornithine and urea, and aberrant arginase activity is implicated in various diseases such as erectile dysfunction, asthma, atherosclerosis, and cerebral malaria. Accordingly, arginase inhibitors may be therapeutically useful. Continuing our efforts to expand the chemical space of arginase inhibitor design and inspired by the binding of 2-(difluoromethyl)-L-ornithine to human arginase I, we now report the first study of the binding of {alpha},{alpha}-disubstituted amino acids to arginase. Specifically, we report the design, synthesis, and assay of racemic 2-amino-6-borono-2-methylhexanoic acid and racemic 2-amino-6-borono-2-(difluoromethyl)hexanoic acid. X-ray crystal structures of human arginase Imore » and Plasmodium falciparum arginase complexed with these inhibitors reveal the exclusive binding of the L-stereoisomer; the additional {alpha}-substituent of each inhibitor is readily accommodated and makes new intermolecular interactions in the outer active site of each enzyme. Therefore, this work highlights a new region of the protein surface that can be targeted for additional affinity interactions, as well as the first comparative structural insights on inhibitor discrimination between a human and a parasitic arginase.« less

General Linker Diversification Approach to Bivalent Ligand Assembly: Generation of an Array of Ligands for the Cation-Independent Mannose 6-Phosphate Receptor.

PubMed

Fei, Xiang; Zavorka, Megan E; Malik, Guillaume; Connelly, Christopher M; MacDonald, Richard G; Berkowitz, David B

2017-08-18

A generalized strategy is presented for the rapid assembly of a set of bivalent ligands with a variety of linking functionalities from a common monomer. Herein, an array of phosphatase-inert mannose-6-phosphonate-presenting ligands for the cation-independent-mannose 6-phosphate receptor (CI-MPR) is constructed. Receptor binding affinity varies with linking functionality-the simple amide and 1,5-triazole(tetrazole) being preferred over the 1,4-triazole. This approach is expected to find application across chemical biology, particularly in glycoscience, wherein multivalency often governs molecular recognition.

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

PubMed

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.

The Possibility of Using Composite Nanoparticles in High Energy Materials

NASA Astrophysics Data System (ADS)

Komarova, M. V.; Vorozhtsov, A. B.; Wakutin, A. G.

2017-01-01

The effect of nanopowders on the burning rate varying with the metal content in mixtures of different high energy composition is investigated. Experiments were performed on compositions based on an active tetrazol binder and electroexplosive nanoaluminum with addition of copper, nickel, or iron nanopowders, and of Al-Ni, Al-Cu, or Al-Fe composite nanoparticles produced by electrical explosion of heterogeneous metal wires. The results obtained from thermogravimetric analysis of model metal-based compositions are presented. The advantages of the composite nanoparticles and the possibility of using them in high energy materials are discussed.

Derivatives of Δ 2-pyrazoline-products of 1,5-diaminotetrazole interaction with chalcone: Molecular structure and spectral properties

NASA Astrophysics Data System (ADS)

Kolos, N. N.; Paponov, B. V.; Orlov, V. D.; Lvovskaya, M. I.; Doroshenko, A. O.; Shishkin, O. V.

2006-03-01

1,5-diaminotetrazole at conditions of its interaction with chalcones (1,3-diphenylpropenones) in hot DMF undergoes Dimroth rearrangement to 5-tetrazolylhydrazine, which results in formation of 1-(5-tetrazolyl)-3,5-diaryl-Δ 2-pyrazolines ( I). Structure of the obtained products was confirmed by their parallel synthesis and X-ray structural analysis. Unusual fluorescence behavior of the tetrazolopyrazolynes in polar solvents was attributed to the dissociation of their highly acidic tetrazole N-H group. The last hypothesis was confirmed at the investigation of the protolytic interactions of I with tertiary amine.

The flight performance of the Galileo orbiter USO

NASA Technical Reports Server (NTRS)

Morabito, D. D.; Krisher, T. P.; Asmar, S. W.

1993-01-01

Results are presented from an analysis of radio metric data received by the DSN stations from the Galileo spacecraft using an Ultrastable Oscillator (USO) as a signal source. These results allow the health and performance of the Galileo USO to be evaluated, and are used to calibrate this Radio Science instrument and the data acquired for Radio Science experiments such as the Red-shift Observation, Solar Conjunction, and Jovian occultations. Estimates for the USO-referenced spacecraft-transmitted frequency and frequency stability were made for 82 data acquisition passes conducted between launch (October 1989) and November 1991. Analyses of the spacecraft-transmitted frequencies show that the USO is behaving as expected. The USO was powered off and then back on in August 1991 with no adverse effect on its performance. The frequency stabilities measured by Allan deviation are consistent with expected values due to thermal wideband noise and the USO itself at the appropriate time intervals. The Galileo USO appears to be healthy and functioning normally in a reasonable manner.

The flight performance of the Galileo orbiter USO

NASA Technical Reports Server (NTRS)

Morabito, D. D.; Krisher, T. P.; Asmar, S. W.

1993-01-01

Results are presented in this article from an analysis of radio metric data received by the DSN stations from the Galileo spacecraft using an Ultrastable Oscillator (USO) as a signal source. These results allow the health and performance of the Galileo USO to be evaluated, and are used to calibrate this Radio Science instrument and the data acquired for Radio Science experiments such as the Redshift Observation, Solar Conjunction, and Jovian occultations. Estimates for the USO-referenced, spacecraft-transmitted frequency and frequency stability were made for 82 data acquisition passes conducted between launch (Oct. 1989) and Nov. 1991. Analyses of the spacecraft-transmitted frequencies show that the USO is behaving as expected. The USO was powered off and then back on in Aug. 1991 with no adverse effect on its performance. The frequency stabilities measured by Allan deviation are consistent with expected values due to thermal wideband noise and the USO itself at the appropriate time intervals. The Galileo USO appears to be healthy and functioning normally in a reasonable manner.

Discovery and initial SAR of imidazoquinoxalines as inhibitors of the Src-family kinase p56(Lck).

PubMed

Chen, Ping; Norris, Derek; Iwanowicz, Edwin J; Spergel, Steven H; Lin, James; Gu, Henry H; Shen, Zhongqi; Wityak, John; Lin, Tai-An; Pang, Suhong; De Fex, Henry F; Pitt, Sidney; Shen, Ding Ren; Doweyko, Arthur M; Bassolino, Donna A; Roberge, Jacques Y; Poss, Michael A; Chen, Bang-Chi; Schieven, Gary L; Barrish, Joel C

2002-05-20

We have identified a novel series of 1,5-imidazoquinoxalines as inhibitors of Lck with excellent potency (IC50s<5 nM) as well as good cellular activity against T-cell proliferation (IC50s<1 microM). Structure-activity studies demonstrate the requirement for the core heterocycle in addition to an optimal 2,6-disubstituted aniline group.

Core Scientific Effort for Biosurface Studies (TASK I).

DTIC Science & Technology

1992-06-30

using acrylamide (I) and both monosubstituted and disubstituted (on nitrogen) acrylamide derivatives (II and LI). CH2 = CH-CO-NH2 CH2 = CH-CO-NHR...of seven different monomers onto poly(ethylene terephthalate), PET. The grafted monomers are: acrylamide , N- isopropylacrylamide, N,N...comprehensive study (as an M.S. thesis) of the grafting of acrylamide on to surface- treated polyolefins is nearing completion. Acrylamide can be

Facile access to unnatural dipeptide-alcohols based on cis-2,5-disubstituted pyrrolidines.

PubMed

Jia, Yan-Yan; Li, Xiao-Ye; Wang, Ping-An; Wen, Ai-Dong

2015-02-11

Well-defined unnatural dipeptide-alcohols based on a cis-2,5-disubstitued pyrrolidine backbone were synthesized from commercially available starting materials meso-diethyl-2,5-dibromoadipate, (S)-(-)-1-phenylethylamine, and phenylalaninol. The structures of these unnatural dipeptide-alcohols are supported by HRMS, 1H- and 13C-NMR spectroscopy. These unnatural dipeptide-alcohols can act as building blocks for peptidomimetics.

Novel 5-aryl-1,3-dihydro-indole-2-thiones. potent, orally active progesterone receptor agonists.

PubMed

Fensome, Andrew; Koko, Marci; Wrobel, Jay; Zhang, Puwen; Zhang, Zhiming; Cohen, Jeffrey; Lundeen, Scott; Rudnick, Kelly; Zhu, Yuan; Winneker, Richard

2003-04-07

During the course of our studies on 3,3-disubstituted-5-aryloxindoles derived progesterone receptor (PR) antagonists we discovered that changing the amide funtionality to a thio-amide resulted in compounds displaying potent PR agonist activity. In this communication, the synthesis, structure activity relationships (SAR) and in vivo activity of various 5-arylthio-oxindoles will be discussed.

Structural analyses of Candida albicans sterol 14α-demethylase complexed with azole drugs address the molecular basis of azole-mediated inhibition of fungal sterol biosynthesis

PubMed Central

Hargrove, Tatiana Y.; Friggeri, Laura; Wawrzak, Zdzislaw; Qi, Aidong; Hoekstra, William J.; Schotzinger, Robert J.; York, John D.; Guengerich, F. Peter; Lepesheva, Galina I.

2017-01-01

With some advances in modern medicine (such as cancer chemotherapy, broad exposure to antibiotics, and immunosuppression), the incidence of opportunistic fungal pathogens such as Candida albicans has increased. Cases of drug resistance among these pathogens have become more frequent, requiring the development of new drugs and a better understanding of the targeted enzymes. Sterol 14α-demethylase (CYP51) is a cytochrome P450 enzyme required for biosynthesis of sterols in eukaryotic cells and is the major target of clinical drugs for managing fungal pathogens, but some of the CYP51 key features important for rational drug design have remained obscure. We report the catalytic properties, ligand-binding profiles, and inhibition of enzymatic activity of C. albicans CYP51 by clinical antifungal drugs that are used systemically (fluconazole, voriconazole, ketoconazole, itraconazole, and posaconazole) and topically (miconazole and clotrimazole) and by a tetrazole-based drug candidate, VT-1161 (oteseconazole: (R)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(2,2,2-trifluoroethoxy)phenyl)pyridin-2-yl)propan-2-ol). Among the compounds tested, the first-line drug fluconazole was the weakest inhibitor, whereas posaconazole and VT-1161 were the strongest CYP51 inhibitors. We determined the X-ray structures of C. albicans CYP51 complexes with posaconazole and VT-1161, providing a molecular mechanism for the potencies of these drugs, including the activity of VT-1161 against Candida krusei and Candida glabrata, pathogens that are intrinsically resistant to fluconazole. Our comparative structural analysis outlines phylum-specific CYP51 features that could direct future rational development of more efficient broad-spectrum antifungals. PMID:28258218

Decomposition of energetic chemicals contaminated with iron or stainless steel.

PubMed

Chervin, Sima; Bodman, Glenn T; Barnhart, Richard W

2006-03-17

Contamination of chemicals or reaction mixtures with iron or stainless steel is likely to take place during chemical processing. If energetic and thermally unstable chemicals are involved in a manufacturing process, contamination with iron or stainless steel can impact the decomposition characteristics of these chemicals and, subsequently, the safety of the processes, and should be investigated. The goal of this project was to undertake a systematic approach to study the impact of iron or stainless steel contamination on the decomposition characteristics of different chemical classes. Differential scanning calorimetry (DSC) was used to study the decomposition reaction by testing each chemical pure, and in mixtures with iron and stainless steel. The following classes of energetic chemicals were investigated: nitrobenzenes, tetrazoles, hydrazines, hydroxylamines and oximes, sulfonic acid derivatives and monomers. The following non-energetic groups were investigated for contributing effects: halogens, hydroxyls, amines, amides, nitriles, sulfonic acid esters, carbonyl halides and salts of hydrochloric acid. Based on the results obtained, conclusions were drawn regarding the sensitivity of the decomposition reaction to contamination with iron and stainless steel for the chemical classes listed above. It was demonstrated that the most sensitive classes are hydrazines and hydroxylamines/oximes. Contamination of these chemicals with iron or stainless steel not only destabilizes them, leading to decomposition at significantly lower temperatures, but also sometimes causes increased severity of the decomposition. The sensitivity of nitrobenzenes to contamination with iron or stainless steel depended upon the presence of other contributing groups: the presence of such groups as acid chlorides or chlorine/fluorine significantly increased the effect of contamination on decomposition characteristics of nitrobenzenes. The decomposition of sulfonic acid derivatives and tetrazoles was not impacted by presence of iron or stainless steel.

The non-biphenyl-tetrazole angiotensin AT1 receptor antagonist eprosartan is a unique and robust inverse agonist of the active state of the AT1 receptor.

PubMed

Takezako, Takanobu; Unal, Hamiyet; Karnik, Sadashiva S; Node, Koichi

2018-03-23

Conditions such as hypertension and renal allograft rejection are accompanied by chronic, agonist-independent, signalling by angiotensin II AT 1 receptors. The current treatment paradigm for these diseases entails the preferred use of inverse agonist AT 1 receptor blockers (ARBs). However, variability in the inverse agonist activities of common biphenyl-tetrazole ARBs for the active state of AT 1 receptors often leads to treatment failure. Therefore, characterization of robust inverse agonist ARBs for the active state of AT 1 receptors is necessary. To identify the robust inverse agonist for active state of AT 1 receptors and its molecular mechanism, we performed site-directed mutagenesis, competition binding assay, inositol phosphate production assay and molecular modelling for both ground-state wild-type AT 1 receptors and active-state N111G mutant AT 1 receptors. Although candesartan and telmisartan exhibited weaker inverse agonist activity for N111G- compared with WT-AT 1 receptors, only eprosartan exhibited robust inverse agonist activity for both N111G- and WT- AT 1 receptors. Specific ligand-receptor contacts for candesartan and telmisartan are altered in the active-state N111G- AT 1 receptors compared with the ground-state WT-AT 1 receptors, suggesting an explanation of their attenuated inverse agonist activity for the active state of AT 1 receptors. In contrast, interactions between eprosartan and N111G-AT 1 receptors were not significantly altered, and the inverse agonist activity of eprosartan was robust. Eprosartan may be a better therapeutic option than other ARBs. Comparative studies investigating eprosartan and other ARBs for the treatment of diseases caused by chronic, agonist-independent, AT 1 receptor activation are warranted. © 2018 The British Pharmacological Society.

Structural analyses of Candida albicans sterol 14α-demethylase complexed with azole drugs address the molecular basis of azole-mediated inhibition of fungal sterol biosynthesis.

PubMed

Hargrove, Tatiana Y; Friggeri, Laura; Wawrzak, Zdzislaw; Qi, Aidong; Hoekstra, William J; Schotzinger, Robert J; York, John D; Guengerich, F Peter; Lepesheva, Galina I

2017-04-21

With some advances in modern medicine (such as cancer chemotherapy, broad exposure to antibiotics, and immunosuppression), the incidence of opportunistic fungal pathogens such as Candida albicans has increased. Cases of drug resistance among these pathogens have become more frequent, requiring the development of new drugs and a better understanding of the targeted enzymes. Sterol 14α-demethylase (CYP51) is a cytochrome P450 enzyme required for biosynthesis of sterols in eukaryotic cells and is the major target of clinical drugs for managing fungal pathogens, but some of the CYP51 key features important for rational drug design have remained obscure. We report the catalytic properties, ligand-binding profiles, and inhibition of enzymatic activity of C. albicans CYP51 by clinical antifungal drugs that are used systemically (fluconazole, voriconazole, ketoconazole, itraconazole, and posaconazole) and topically (miconazole and clotrimazole) and by a tetrazole-based drug candidate, VT-1161 (oteseconazole: ( R )-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1 H -tetrazol-1-yl)-1-(5-(4-(2,2,2-trifluoroethoxy)phenyl)pyridin-2-yl)propan-2-ol). Among the compounds tested, the first-line drug fluconazole was the weakest inhibitor, whereas posaconazole and VT-1161 were the strongest CYP51 inhibitors. We determined the X-ray structures of C. albicans CYP51 complexes with posaconazole and VT-1161, providing a molecular mechanism for the potencies of these drugs, including the activity of VT-1161 against Candida krusei and Candida glabrata , pathogens that are intrinsically resistant to fluconazole. Our comparative structural analysis outlines phylum-specific CYP51 features that could direct future rational development of more efficient broad-spectrum antifungals. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

NMR investigation and theoretical calculations of the solvent effect on the conformation of valsartan

NASA Astrophysics Data System (ADS)

Chashmniam, Saeed; Tafazzoli, Mohsen

2017-11-01

Structure and conformational properties of valsartan were studied by advanced NMR techniques and quantum calculation methods. Potential energy scanning using B3LYP/6-311++g** and B3LYP-D3/6-311++g** methods were performed and four conformers (V1-V4) at minimum points of PES diagram were observed. According to the NMR spectra in acetone-d6, there are two conformers (M and m) with m/M = 0.52 ratio simultaneously and energy barriers of the two conformers were predicted from chemical shifts and multiplicities. While, intramolecular hydrogen bond at tetrazole ring and carboxylic groups prevent the free rotation on N6sbnd C11 bond in M-conformer, this bond rotates freely in m-conformer. On the other hand, intramolecular hydrogen bond at carbonyl and carboxylic acid can be observed at m-conformer. So, different intramolecular hydrogen bond is the reason for the stability of both M and m structures. Quite interestingly, 1H NMR spectra in CDCl3 show two distinct conformers (N and n) with unequal ratio which are differ from M-m conformers. Also, intramolecular hydrogen bond seven-member ring involving five-membered tetrazole ring and carboxylic acid group observed in both N and n-conformers Solvent effect, by using a set of polar and non-polar solvents including DMSO-d6, methanol-d4, benzene-d6, THF-d8, nitromethane-d3, methylene chloride-d2 and acetonitrile-d3 were investigated. NMR parameters include chemical shifts and spin-spin coupling constants were obtained from a set of 2D NMR spectra (H-H COSY, HMQC and HMBC). For this purpose, several DFT functionals from LDA, GGA and hybrid categories were used which the hybrid method showed better agreement with experiment values.

Unique binding behavior of the recently approved angiotensin II receptor blocker azilsartan compared with that of candesartan

PubMed Central

Miura, Shin-ichiro; Okabe, Atsutoshi; Matsuo, Yoshino; Karnik, Sadashiva S; Saku, Keijiro

2014-01-01

The angiotensin II type 1 (AT1) receptor blocker (ARB) candesartan strongly reduces blood pressure (BP) in patients with hypertension and has been shown to have cardioprotective effects. A new ARB, azilsartan, was recently approved and has been shown to provide a more potent 24-h sustained antihypertensive effect than candesartan. However, the molecular interactions of azilsartan with the AT1 receptor that could explain its strong BP-lowering activity are not yet clear. To address this issue, we examined the binding affinities of ARBs for the AT1 receptor and their inverse agonist activity toward the production of inositol phosphate (IP), and we constructed docking models for the interactions between ARBs and the receptor. Azilsartan, unlike candesartan, has a unique moiety, a 5-oxo-1,2,4-oxadiazole, in place of a tetrazole ring. Although the results regarding the binding affinities of azilsartan and candesartan demonstrated that these ARBs interact with the same sites in the AT1 receptor (Tyr113, Lys199 and Gln257), the hydrogen bonding between the oxadiazole of azilsartan-Gln257 is stronger than that between the tetrazole of candesartan-Gln257, according to molecular docking models. An examination of the inhibition of IP production by ARBs using constitutively active mutant receptors indicated that inverse agonist activity required azilsartan–Gln257 interaction and that azilsartan had a stronger interaction with Gln257 than candesartan. Thus, we speculate that azilsartan has a unique binding behavior to the AT1 receptor due to its 5-oxo-1,2,4-oxadiazole moiety and induces stronger inverse agonism. This property of azilsartan may underlie its previously demonstrated superior BP-lowering efficacy compared with candesartan and other ARBs. PMID:23034464

Unique binding behavior of the recently approved angiotensin II receptor blocker azilsartan compared with that of candesartan.

PubMed

Miura, Shin-ichiro; Okabe, Atsutoshi; Matsuo, Yoshino; Karnik, Sadashiva S; Saku, Keijiro

2013-02-01

The angiotensin II type 1 (AT(1)) receptor blocker (ARB) candesartan strongly reduces blood pressure (BP) in patients with hypertension and has been shown to have cardioprotective effects. A new ARB, azilsartan, was recently approved and has been shown to provide a more potent 24-h sustained antihypertensive effect than candesartan. However, the molecular interactions of azilsartan with the AT(1) receptor that could explain its strong BP-lowering activity are not yet clear. To address this issue, we examined the binding affinities of ARBs for the AT(1) receptor and their inverse agonist activity toward the production of inositol phosphate (IP), and we constructed docking models for the interactions between ARBs and the receptor. Azilsartan, unlike candesartan, has a unique moiety, a 5-oxo-1,2,4-oxadiazole, in place of a tetrazole ring. Although the results regarding the binding affinities of azilsartan and candesartan demonstrated that these ARBs interact with the same sites in the AT(1) receptor (Tyr(113), Lys(199) and Gln(257)), the hydrogen bonding between the oxadiazole of azilsartan-Gln(257) is stronger than that between the tetrazole of candesartan-Gln(257), according to molecular docking models. An examination of the inhibition of IP production by ARBs using constitutively active mutant receptors indicated that inverse agonist activity required azilsartan-Gln(257) interaction and that azilsartan had a stronger interaction with Gln(257) than candesartan. Thus, we speculate that azilsartan has a unique binding behavior to the AT(1) receptor due to its 5-oxo-1,2,4-oxadiazole moiety and induces stronger inverse agonism. This property of azilsartan may underlie its previously demonstrated superior BP-lowering efficacy compared with candesartan and other ARBs.

Initial mechanisms for the decomposition of electronically excited energetic materials: 1,5′-BT, 5,5′-BT, and AzTT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yuan, Bing; Yu, Zijun; Bernstein, Elliot R., E-mail: erb@lamar.Colostate.edu

2015-03-28

Decomposition of nitrogen-rich energetic materials 1,5′-BT, 5,5′-BT, and AzTT (1,5′-Bistetrazole, 5,5′-Bistetrazole, and 5-(5-azido-(1 or 4)H-1,2,4-triazol-3-yl)tetrazole, respectively), following electronic state excitation, is investigated both experimentally and theoretically. The N{sub 2} molecule is observed as an initial decomposition product from the three materials, subsequent to UV excitation, with a cold rotational temperature (<30 K). Initial decomposition mechanisms for these three electronically excited materials are explored at the complete active space self-consistent field (CASSCF) level. Potential energy surface calculations at the CASSCF(12,8)/6-31G(d) level illustrate that conical intersections play an essential role in the decomposition mechanism. Electronically excited S{sub 1} molecules can non-adiabatically relaxmore » to their ground electronic states through (S{sub 1}/S{sub 0}){sub CI} conical intersections. 1,5′-BT and 5,5′-BT materials have several (S{sub 1}/S{sub 0}){sub CI} conical intersections between S{sub 1} and S{sub 0} states, related to different tetrazole ring opening positions, all of which lead to N{sub 2} product formation. The N{sub 2} product for AzTT is formed primarily by N–N bond rupture of the –N{sub 3} group. The observed rotational energy distributions for the N{sub 2} products are consistent with the final structures of the respective transition states for each molecule on its S{sub 0} potential energy surface. The theoretically derived vibrational temperature of the N{sub 2} product is high, which is similar to that found for energetic salts and molecules studied previously.« less

Rapid Asymmetric Synthesis of Disubstituted Allenes by Coupling of Flow‐Generated Diazo Compounds and Propargylated Amines

PubMed Central

Poh, Jian‐Siang; Makai, Szabolcs; von Keutz, Timo; Tran, Duc N.; Battilocchio, Claudio; Pasau, Patrick

2017-01-01

Abstract We report herein the asymmetric coupling of flow‐generated unstabilized diazo compounds and propargylated amine derivatives, using a new pyridinebis(imidazoline) ligand, a copper catalyst and base. The reaction proceeds rapidly, generating chiral allenes in 10–20 minutes with high enantioselectivity (89–98 % de/ee), moderate yields and a wide functional group tolerance. PMID:28075518

Liquid Crystalline Polymers Containing Heterocycloalkane Mesogens. 2. Side-Chain Liquid Crystalline Polysiloxanes Containing 2,5-Disubstituted-1,3-Dioxane Mesogens.

DTIC Science & Technology

1986-10-01

units and an aliphatic spacer containing eleven and respectively, ten methylene units were synthesized. Their phase behavior was studied by differential...scanning calorimetry and optical polarization microscopy, and compared with the phase behavior of the polysiloxanes and copolysiloxanes containing 4...containing eleven and respectively, ten methylene -units were synthesized. Their phase behavior was studied by differential * scanning calorimetry

Gold-catalyzed three-component annulation: efficient synthesis of highly functionalized dihydropyrazoles from alkynes, hydrazines, and aldehydes or ketones.

PubMed

Suzuki, Yamato; Naoe, Saori; Oishi, Shinya; Fujii, Nobutaka; Ohno, Hiroaki

2012-01-06

Polysubstituted dihydropyrazoles were directly obtained by a gold-catalyzed three-component annulation. This reaction consists of a Mannich-type coupling of alkynes with N,N'-disubstituted hydrazines and aldehydes/ketones followed by intramolecular hydroamination. Cascade cyclization using 1,2-dialkynylbenzene derivatives as the alkyne component was also performed producing fused tricyclic dihydropyrazoles in good yields. © 2011 American Chemical Society

Synthesis, characterization, single crystal X-ray and DFT analysis of disubstituted phosphorodithioates

NASA Astrophysics Data System (ADS)

Kour, Mandeep; Kumar, Sandeep; Feddag, Ahmed; Andotra, Savit; Chouaih, Abdelkader; Gupta, Vivek K.; Kant, Rajni; Pandey, Sushil K.

2018-04-01

Disubstituted phosphorodithioates of the type [{(2,5-CH3)2C6H3O}2PS2HNEt3] (1) and [{(3,5-CH3)2C6H3O)2(PS2)}2] (2) were synthesized and characterized by IR and NMR (1H,13C and 31P) spectroscopic studies and as single crystal X-ray analysis. The compound 1 crystallizes in monoclinic space group P21/c whereas compound 2 crystallizes in triclinic space group Pbar1. The X-ray analysis reveals that in compound 1 phosphorus atom is coordinated to the two S and two O atoms to form tetrahedral geometry. The structure is stabilized by cation-anion Nsbnd H⋯S hydrogen bonded interactions. In compound 2, the two phosphorus atoms have a distorted tetrahedral geometry coordinated to two (3,5-CH3)2C6H3O groups. The molecule possesses a crystallographic center of symmetry and consists of zig-zag array of Sdbnd Psbnd Ssbnd Ssbnd Pdbnd S linkages with two diphenyldithiophosphate moieties in the trans configuration. Molecular geometries, HOMO-LUMO analysis and molecular electrostatic potential of compounds 1 and 2 are investigated by theoretical calculations using B3LYP functional with the 6-311G basis combination set in the ground state and compared with the experimental values.

Insights into the structural/conformational requirements of cytotoxic oxadiazoles as potential chemotherapeutic target binding agents

NASA Astrophysics Data System (ADS)

Alikhani, Radin; Razzaghi-Asl, Nima; Ramazani, Ali; Hosseinzadeh, Zahra

2018-07-01

A few novel previously synthesized 2,5-disubstituted 1,3,4-oxadiazoles with cytotoxic activity (1-17) were subjected to combined docking/quantum mechanical studies against chemotherapeutic targets. Selected macromolecular targets were those that were previously known to be inhibited by 1,3,4-oxadiazoles. Within this work, favorable binding modes/affinities of the oxadiazoles toward validated cancer targets were elucidated. Some oxadiazole structures exhibited ΔGbs comparable to or stronger than crystallographic ligands that were previously demonstrated to inhibit such targets. On the basis of obtained results, a general structure activity/binding relationship (SAR/SBR) was developed and a few 2,5-disubstituted 1,3,4-oxadiazole structures were proposed and virtually validated as potential cytotoxic candidates. To get more insight into structure binding relationship of candidate molecules within best correlated targets, docked conformation of the best in silico in vitro correlated oxadiazole structure was analyzed in terms of intermolecular binding energy components by functional B3LYP in association with split valence basis set using polarization functions (Def2-SVP). We believe that such modeling studies may be complementary to our previous results on the synthesis and cytotoxicity assessment of novel 1,3,4-oxadiazole derivatives through extending the scope of privileged structures toward designing new potential anti-tumor compounds.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hai, Yang; Christianson, David W.

Leishmaniaarginase is a potential drug target for the treatment of leishmaniasis because this binuclear manganese metalloenzyme initiatesde novopolyamine biosynthesis by catalyzing the hydrolysis of L-arginine to generate L-ornithine and urea. The product L-ornithine subsequently undergoes decarboxylation to yield putrescine, which in turn is utilized for spermidine biosynthesis. Polyamines such as spermidine are essential for the growth and survival of the parasite, so inhibition of enzymes in the polyamine-biosynthetic pathway comprises an effective strategy for treating parasitic infections. To this end, two X-ray crystal structures ofL. mexicanaarginase complexed with α,α-disubstituted boronic amino-acid inhibitors based on the molecular scaffold of 2-(S)-amino-6-boronohexanoic acidmore » are now reported. Structural comparisons with human and parasitic arginase complexes reveal interesting differences in the binding modes of the additional α-substituents,i.e.the D side chains, of these inhibitors. Subtle differences in the three-dimensional contours of the outer active-site rims among arginases from different species lead to different conformations of the D side chains and thus different inhibitor-affinity trends. The structures suggest that it is possible to maintain affinity while fine-tuning intermolecular interactions of the D side chain of α,α-disubstituted boronic amino-acid inhibitors in the search for isozyme-specific and species-specific arginase inhibitors.« less

2, 5-Disubstituted phthalimides: design, synthesis and anticonvulsant activity in scPTZ and MES models.

PubMed

Saadabadi, Atefeh; Kohen, Babak; Irandoust, Maryam; Shafaroudi, Hamed; Mohammadpour, Tara; Rezayat, Mahdi; Davood, Asghar

2018-05-15

In this study, fifteenth new 2,5-disubstituted analgouges of phthalimide were designed and synthesized using the appropriate synthetic route to evaluate anticonvulsant activity against the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) compare to phenytoin as a positive control. The structures of the synthesized compounds were confirmed by FT-IR, H-NMR, C-NMR and MASS spectroscopy. All the tested compounds were found to be effective in the PTZ model at the dose of 60 mg/kg and most of the compounds showed protection against MES test indicative of their ability to inhibit the seizure spread at the all dose ranges. Compound 3 has illustrated the best efficacy among all compounds and showed more potency than phenytoin in clonic seizure and was potent as phenytoin in tonic seizure. Using a model of the Na channel, these derivatives were docked in the active site. Docking studies displayed that all synthesized compounds have more negative binding energy compare to reference drug and inhibition-constant less than phenytoin that means they can block the receptor more efficiently and usually form hydrophobic interactions or hydrogen binding interaction frequently with the domains I, II, III and rarely with domain IV. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

SAR study on N2,N4-disubstituted pyrimidine-2,4-diamines as effective CDK2/CDK9 inhibitors and antiproliferative agents† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c8ra01440j

PubMed Central

Jing, Liandong; Tang, Yanbo; Goto, Masuo; Lee, Kuo-Hsiung

2018-01-01

Cyclin-dependent kinases (CDKs) are pivotal kinases in cell cycle transition and gene transcription. A series of N2,N4-diphenylpyrimidine-2,4-diamines were previously identified as potent CDK2/CDK9 inhibitors. To explore the SAR of this structural prototype, twenty-four novel N2,N4-disubstituted pyrimidine-2,4-diamines were designed and synthesized. Among them, twenty-one compounds exhibited potent inhibitory activities against both CDK2/cyclin A and CDK9/cyclin T1 systems, and the most potent CDK2 and CDK9 inhibitors, 3g and 3c, showed IC50 values of 83 nM and 65 nM respectively. Most of these compounds displayed significant inhibition against the tested tumor cell lines in the SRB assay, and in particular, remained active against the triple-negative breast cancer (TNBC) cell line MDA-MB-231. Flow cytometer analysis of compounds 2a, 2d and 3b in MDA-MB-231 cells indicated that these compounds induced cell cycle arrest in G2/M phase. Docking studies on compound 3g were performed, which provided conducive clues for further molecular optimization. PMID:29682280

Measurements of Ultra-Stable Oscillator (USO) Allan Deviations in Space

NASA Technical Reports Server (NTRS)

Enzer, Daphna G.; Klipstein, William M.; Wang, Rabi T.; Dunn, Charles E.

2013-01-01

Researchers have used data from the GRAIL mission to the Moon to make the first in-flight verification of ultra-stable oscillators (USOs) with Allan deviation below 10 13 for 1-to-100-second averaging times. USOs are flown in space to provide stable timing and/or navigation signals for a variety of different science and programmatic missions. The Gravity Recovery and Interior Laboratory (GRAIL) mission is flying twin spacecraft, each with its own USO and with a Ka-band crosslink used to measure range fluctuations. Data from this crosslink can be combined in such a way as to give the relative time offsets of the two spacecrafts USOs and to calculate the Allan deviation to describe the USOs combined performance while orbiting the Moon. Researchers find the first direct in-space Allan deviations below 10(exp -13) for 1-to-100-second averaging times comparable to pre-launch data, and better than measurements from ground tracking of an X-band carrier coherent with the USO. Fluctuations in Earth s atmosphere limit measurement performance in direct-to-Earth links. Inflight USO performance verification was also performed for GRAIL s parent mission, the Gravity Recovery and Climate Experiment (GRACE), using both Kband and Ka-band crosslinks.

Stereodivergent Aminocatalytic Synthesis of Z- and E-Trisubstituted Double Bonds from Alkynals.

PubMed

Marzo, Leyre; Luis-Barrera, Javier; Mas-Ballesté, Rubén; Ruano, José Luis García; Alemán, José

2016-11-07

A highly diastereoselective synthesis of trisubstituted Z- or E-enals, which are important intermediates in organic synthesis, as well as being present in natural products, is described using different alkynals and nucleophiles as starting materials. Diastereocontrol is mainly governed by the appropriate catalyst. Therefore, those reactions controlled by steric effects, such as the Jørgensen-Hayashi's catalyst, give access to E isomers, and those catalysts that facilitate hydrogen bonding, such as tetrazol-pyrrolidine Ley's catalyst, allow the synthesis of Z isomers. A stereochemical model based on DFT calculations is proposed. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rhodium-catalyzed asymmetric hydroboration of γ,δ-unsaturated amide derivatives: δ-borylated amides.

PubMed

Hoang, G L; Zhang, S; Takacs, J M

2018-05-08

γ,δ-Unsaturated amides in which the alkene moiety bears an aryl or heteroaryl substituent undergo regioselective rhodium-catalyzed δ-borylation by pinacolborane to afford chiral secondary benzylic boronic esters. The results contrast the γ-borylation of γ,δ-unsaturated amides in which the disubstituted alkene moiety bears only alkyl substituents; the reversal in regiochemistry is coupled with a reversal in the sense of π-facial selectivity.

Diastereoselective synthesis of chiral 1,3-cyclohexadienals

PubMed Central

de la Granja, Ángela P.; Capitán, M. Carmen; Moro, R. F.; Marcos, Isidro S.; Garrido, Narciso M.; Sanz, Francisca; Calle, Emilio

2018-01-01

A novel approach to the production of chiral 1,3-cyclohexadienals has been developed. The organocatalysed asymmetric reaction of different β-disubstituted-α,β-unsaturated aldehydes with a chiral α,β-unsaturated aldehyde in the presence of a Jørgensen-Hayashi organocatalyst provides easy and stereocontrolled access to the cyclohexadienal backbone. This method allows for the synthesis of potential photoprotective chiral 1,3-cyclohexadienals and extra extended conjugation compounds in a simple manner. PMID:29438416

Diastereoselective synthesis of chiral 1,3-cyclohexadienals.

PubMed

Urosa, Aitor; Tobal, Ignacio E; de la Granja, Ángela P; Capitán, M Carmen; Moro, R F; Marcos, Isidro S; Garrido, Narciso M; Sanz, Francisca; Calle, Emilio; Díez, David

2018-01-01

A novel approach to the production of chiral 1,3-cyclohexadienals has been developed. The organocatalysed asymmetric reaction of different β-disubstituted-α,β-unsaturated aldehydes with a chiral α,β-unsaturated aldehyde in the presence of a Jørgensen-Hayashi organocatalyst provides easy and stereocontrolled access to the cyclohexadienal backbone. This method allows for the synthesis of potential photoprotective chiral 1,3-cyclohexadienals and extra extended conjugation compounds in a simple manner.

Rapid Asymmetric Synthesis of Disubstituted Allenes by Coupling of Flow-Generated Diazo Compounds and Propargylated Amines.

PubMed

Poh, Jian-Siang; Makai, Szabolcs; von Keutz, Timo; Tran, Duc N; Battilocchio, Claudio; Pasau, Patrick; Ley, Steven V

2017-02-06

We report herein the asymmetric coupling of flow-generated unstabilized diazo compounds and propargylated amine derivatives, using a new pyridinebis(imidazoline) ligand, a copper catalyst and base. The reaction proceeds rapidly, generating chiral allenes in 10-20 minutes with high enantioselectivity (89-98 % de/ee), moderate yields and a wide functional group tolerance. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Shallow-water habitats as sources of fallback foods for hominins.

PubMed

Wrangham, Richard; Cheney, Dorothy; Seyfarth, Robert; Sarmiento, Esteban

2009-12-01

Underground storage organs (USOs) have been proposed as critical fallback foods for early hominins in savanna, but there has been little discussion as to which habitats would have been important sources of USOs. USOs consumed by hominins could have included both underwater and underground storage organs, i.e., from both aquatic and terrestrial habitats. Shallow aquatic habitats tend to offer high plant growth rates, high USO densities, and relatively continuous USO availability throughout the year. Baboons in the Okavango delta use aquatic USOs as a fallback food, and aquatic or semiaquatic USOs support high-density human populations in various parts of the world. As expected given fossilization requisites, the African early- to mid-Pleistocene shows an association of Homo and Paranthropus fossils with shallow-water and flooded habitats where high densities of plant-bearing USOs are likely to have occurred. Given that early hominins in the tropics lived in relatively dry habitats, while others occupied temperate latitudes, ripe, fleshy fruits of the type preferred by African apes would not normally have been available year round. We therefore suggest that water-associated USOs were likely to have been key fallback foods, and that dry-season access to aquatic habitats would have been an important predictor of hominin home range quality. This study differs from traditional savanna chimpanzee models of hominin origins by proposing that access to aquatic habitats was a necessary condition for adaptation to savanna habitats. It also raises the possibility that harvesting efficiency in shallow water promoted adaptations for habitual bipedality in early hominins.

Liquid Crystalline Polymers Containing Heterocycloalkane Mesogens. 1. Side-Chain Liquid Crystalline Polymethacrylates and Polycrylates Containing 2,5-Disubstituted-1,3-Dioxane Mesogens.

DTIC Science & Technology

1986-10-01

Report No. 2 Liquid Crystalline Polymers Containing Heterocycloalkane Mesogeus 1. Side-Chain Liquid Crystalline Polymethacrylates and . Polyacrylates...8217. " "-"-"-" " "" ’CS" i Liquid Crystalline Polymers Containing Heterocycloalkane Mesogens 1. Side-Chain Liquid Crystalline Polymethacrylates and Polyacrylates...University Cleveland, OH 44106 ABSTRACT Polymethacrylates and polyacrylates containing 2-(p-hydroxyphenyl)-5-(p-meth- oxyphenyl)-1,3-dioxane as a

5-Hydroxyindoles by intramolecular alkynol-furan diels-alder cycloaddition.

PubMed

LaPorte, Matthew; Hong, Ki Bum; Xu, Jie; Wipf, Peter

2013-01-04

A convergent approach provides a convenient access to synthetically and biologically useful 3,4-disubstituted 5-hydroxyindoles. The one-pot procedure uses microwave heating to initiate an intramolecular [4 + 2]-cycloaddition of an alkynol segment onto a furan followed by a fragmentation, aromatization, and N-Boc deprotection cascade. Yields range from 15 to 74%, with aromatic substituents providing better conversions. 4-Trimethylsilylated analogues undergo a 1,3-silatropic rearrangement to give the O-TMS ethers.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Jian-Guo; Lee, Patrick K.-M.; Dong, Yu-Hui

Acetohydroxyacid synthase (AHAS; EC 2.2.1.6) is the first enzyme in the biosynthetic pathway of the branched-chain amino acids. It catalyzes the conversion of two molecules of pyruvate into 2-acetolactate or one molecule of pyruvate and one molecule of 2-ketobutyrate into 2-aceto-2-hydroxybutyrate. AHAS requires the cofactors thiamine diphosphate (ThDP), Mg{sup 2+} and FAD for activity. The herbicides that target this enzyme are effective in protecting a broad range of crops from weed species. However, resistance in the field is now a serious problem worldwide. To address this, two new sulfonylureas, monosulfuron and monosulfuron ester, have been developed as commercial herbicides inmore » China. These molecules differ from the traditional sulfonylureas in that the heterocyclic ring attached to the nitrogen atom of the sulfonylurea bridge is monosubstituted rather than disubstituted. The structures of these compounds in complex with the catalytic subunit of Arabidopsis thaliana AHAS have been determined to 3.0 and 2.8 {angstrom}, respectively. In both complexes, these molecules are bound in the tunnel leading to the active site, such that the sole substituent of the heterocyclic ring is buried deepest and oriented towards the ThDP. Unlike the structures of Arabidopsis thaliana AHAS in complex with the classic disubstituted sulfonylureas, where ThDP is broken, this cofactor is intact and present most likely as the hydroxylethyl intermediate.« less

Analysis of South Atlantic Anomaly perturbations on Sentinel-3A Ultra Stable Oscillator. Impact on DORIS phase measurement and DORIS station positioning

NASA Astrophysics Data System (ADS)

Jalabert, Eva; Mercier, Flavien

2018-07-01

DORIS measurements rely on the precise knowledge of the embedded oscillator which is called the Ultra Stable Oscillator (DORIS USO). The important radiations in the South Atlantic Anomaly (SAA) perturb the USO behavior by causing rapid frequency variations when the satellite is flying through the SAA. These variations are not taken into account in standard DORIS processing, since the USO is modelled as a third degree polynomial over 7-10 days. Therefore, there are systematic measurements errors when the satellite passes through SAA. In standard GNSS processing, the clock is directly estimated at each epoch. On Sentinel-3A, the GPS receiver and the DORIS receiver use the same USO. It is thus possible to estimate the behavior of the USO using GPS measurements. This estimated USO behavior can be used in the DORIS processing, instead of the third degree polynomial, hence allowing an estimation of the orbit sensitivity to these USO anomalies. This study shows two main results. First, the SAA effect on the DORIS USO is observed well using GPS measurements. Second, the USO behavior observed with GPS can be used to mitigate the SAA effect. Indeed, when used in Sentinel-3A processing, the resulting DORIS orbit shows improved phase measurements and station positioning for stations inside the SAA (Arequipa and Cachoeira). The phase measurements residuals are improved by up to 10 cm, and station vertical positioning (i.e. on the estimated Up component in the North-East-Up station frame) is improved by up to a few centimeters. However, the orbit itself is not sensitive to the correction because only two stations (out of almost 60) are SAA-sensitive on Sentinel-3A.

Palladium-catalyzed asymmetric quaternary stereocenter formation.

PubMed

Gottumukkala, Aditya L; Matcha, Kiran; Lutz, Martin; de Vries, Johannes G; Minnaard, Adriaan J

2012-05-29

An efficient palladium catalyst is presented for the formation of benzylic quaternary stereocenters by conjugate addition of arylboronic acids to a variety of β,β-disubstituted carbocyclic, heterocyclic, and acyclic enones. The catalyst is readily prepared from PdCl(2), PhBOX, and AgSbF(6), and provides products in up to 99% enantiomeric excess, with good yields. Based on this strategy, (-)-α-cuparenone has been prepared in only two steps. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Selectivity in ligand recognition of G-quadruplex loops.

PubMed

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

2009-03-03

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

Occurrence and significance of decahydroquinolines from dendrobatid poison frogs and a Myrmicine ant: Use of 1H and 13C NMR in their conformational analysis

Treesearch

T.F. Spande; P. Jain; H.M. Garraffo; L.K. Pannell; H.J.C. Yeh; J.W. Daly; S. Fukumoto; K. Imamura; J.A. Torres; R.R. Snelling; T.H. Jones

1999-01-01

Structures for 2,5-disubstituted decahydroquinolines (DHQs) are reported for the two diastereomeric pairs cis-275B (14) and cis-275B' (15) and 5-epi-trans-269AB (18) and trans-269AB (19), all isolated from skin extracts of dendrobatid frogs, and for 5-epi-cis-275B' (16) and 5-epi-trans-275B (17) found in the extracts of virgin queens of a myrmicine ant [...

Copper(II) carboxylate promoted intramolecular diamination of terminal alkenes: improved reaction conditions and expanded substrate scope.

PubMed

Zabawa, Thomas P; Chemler, Sherry R

2007-05-10

The copper(II) carboxylate promoted diamination reaction has been improved by the use of the organic soluble copper(II) neodecanoate [Cu(ND)2]. Cu(ND)2 allowed the less-polar solvent dichloroethane (DCE) to be used, and as a consequence, decomposition of less-reactive substrates could be avoided. High diastereoselectivity was observed in the synthesis of 2,5-disubstituted pyrrolidines. Ureas, bis(anilines), and alpha-amido pyrroles derived from 2-allylaniline could also participate in the diamination reaction.

Synthesis of 2,3-Disubstituted Quinolines via Ketenimine or Carbodiimide Intermediates.

PubMed

Zhao, Hongyang; Xing, Yanpeng; Lu, Ping; Wang, Yanguang

2016-10-10

Cyclopenta[b]quinolines and cyclohexa[b]quinolines were prepared via the reactions of α-diazo ketones with N-(2-cyclopropylidenemethylphenyl)phosphanimines and N-(2-cyclobutylidenemethylphenyl) phosphanimine, respectively. The reaction proceeds in a cascade involving ketenimine formation, 6 π-electron ring closure, and 1,3-alkyl shift. A similar approach was developed for the synthesis of dihydropyrrolo-[2,3-b]quinolines from N-(2-cyclopropylidenemethylphenyl)phosphanimines and isocyanates. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of Enantiomerically Pure 6-Substituted-Piperazine-2-Acetic Acid Esters as Intermediates for Library Production.

PubMed

Chamakuri, Srinivas; Jain, Prashi; Guduru, Shiva Krishna Reddy; Arney, Joseph Winston; MacKenzie, Kevin; Santini, Conrad; Young, Damian W

2018-05-11

Amino acids from the chiral pool have been used to produce a 24-member branch of 2,6-disubstituted piperazine scaffolds suitable for use in compound library production. Each scaffold was obtained as a single absolute stereoisomer in multi-gram quantities. Stereochemistry was confirmed by 2D NMR protocols and enantiomeric purity was determined by chiral HPLC. The scaffolds are intended for use as intermediates in parallel synthesis of small-molecule libraries.

Kinesin spindle protein (KSP) inhibitors. Part 7: Design and synthesis of 3,3-disubstituted dihydropyrazolobenzoxazines as potent inhibitors of the mitotic kinesin KSP.

PubMed

Garbaccio, Robert M; Tasber, Edward S; Neilson, Lou Anne; Coleman, Paul J; Fraley, Mark E; Olson, Christy; Bergman, Jeff; Torrent, Maricel; Buser, Carolyn A; Rickert, Keith; Walsh, Eileen S; Hamilton, Kelly; Lobell, Robert B; Tao, Weikang; South, Vicki J; Diehl, Ronald E; Davide, Joseph P; Yan, Youwei; Kuo, Lawrence C; Li, Chunze; Prueksaritanont, Thomayant; Fernandez-Metzler, Carmen; Mahan, Elizabeth A; Slaughter, Donald E; Salata, Joseph J; Kohl, Nancy E; Huber, Hans E; Hartman, George D

2007-10-15

Observations from two structurally related series of KSP inhibitors led to the proposal and discovery of dihydropyrazolobenzoxazines that possess ideal properties for cancer drug development. The synthesis and characterization of this class of inhibitors along with relevant pharmacokinetic and in vivo data are presented. The synthesis is highlighted by a key [3+2] cycloaddition to form the pyrazolobenzoxazine core followed by diastereospecific installation of a quaternary center.

Excellent acceleration of the Diels-Alder reaction by microwave irradiation for the synthesis of new fluorine-substituted ligands of NMDA receptor.

PubMed

Sasaki, S; Ishibashi, N; Kuwamura, T; Sano, H; Matoba, M; Nisikawa, T; Maeda, M

1998-11-03

A series of 6,11-ethanobenzo[b]quinolizinium derivatives was synthesized through the Diels-Alder reaction between azoniaanthracne and the corresponding 1,1-disubstituted olefin. After a systematic investigation for achieving rapid synthesis, it was found that the reaction is accelerated in polar media such as H2O and trifluoroethanol. In particular, excellent acceleration was effected by microwave irradiation. The new fluorine-substituted ligands thus obtained exhibited potential affinity toward NMDA receptors.

Tandem Reduction/Cyclization of O-Nitrophenyl Propargyl Alcohols-A Novel Synthesis of 2- & 2,4-Disubstituted Quinolines and Application to the Synthesis of Streptonigrin

DTIC Science & Technology

2008-01-01

surrogate” acrolein, which was synthesized from vinyl acetate (Scheme 11, upper equation )31. This mild method was an improvement over their previous work...11, lower equation ). Both cyclizations were facile with N,S-acetals bearing strongly activating groups on aniline. The resulting 2-methylthio...kinetic studies of the MS rearrangement.144 Using a combination of Hammett analysis of substituent effects and solvent isotope effects, Edens concluded

Total synthesis of (+)-ileabethoxazole via an iron-mediated Pauson-Khand [2 + 2 + 1] carbocyclization.

PubMed

Williams, David R; Shah, Akshay A

2014-06-18

Studies describe the total synthesis of (+)-ileabethoxazole (1) using a Stille cross-coupling reaction of propargylic stannanes with 5-iodo-1,3-oxazoles to produce 1,1-disubstituted allenes (11). An iron-mediated [2 + 2 + 1] carbocyclization yields a novel cyclopentenone for elaboration to 1. Site-selective palladium insertion reactions allow for regiocontrolled substitutions of the heterocycle. Asymmetric copper hydride reductions are examined, and strategies for the formation of the central aromatic ring are discussed.

Novel high contrast electrochromic polymer materials based on 3,4-propylenedioxythiophene

NASA Astrophysics Data System (ADS)

Sahoo, Rabindra; Mishra, Sarada P.; Kumar, Anil; Sindhu, S.; Narasimha Rao, K.; Gopal, E. S. R.

2007-09-01

Mono and di allyl and napthyl substituted 3,4-propylenedioxythiophenes were synthesized and polymerized electrochemically. All the monomers were characterized for their molecular structures, and the polymers were characterized for their electrochemical properties. The disubstituted derivatives showed higher contrast than the corresponding mono substituted derivatives. The allyl substituted polymers showed higher contrast and faster switching time than corresponding napthyl substituted derivatives. The presence of the allyl group as the pendant can be used for further functionalization of the polymer.

Structural stability, vibrational, and bonding properties of potassium 1, 1'-dinitroamino-5, 5'-bistetrazolate: An emerging green primary explosive.

PubMed

Yedukondalu, N; Vaitheeswaran, G

2015-08-14

Potassium 1,1'-dinitroamino-5,5'-bistetrazolate (K2DNABT) is a nitrogen rich (50.3% by weight, K2C2N12O4) green primary explosive with high performance characteristics, namely, velocity of detonation (D = 8.33 km/s), detonation pressure (P = 31.7 GPa), and fast initiating power to replace existing toxic primaries. In the present work, we report density functional theory (DFT) calculations on structural, equation of state, vibrational spectra, electronic structure, and absorption spectra of K2DNABT. We have discussed the influence of weak dispersive interactions on structural and vibrational properties through the DFT-D2 method. We find anisotropic compressibility behavior (b

Homo- and heteroleptic bismuth(III/V) thiolates from N-heterocyclic thiones: synthesis, structure and anti-microbial activity.

PubMed

Luqman, Ahmad; Blair, Victoria L; Brammananth, Rajini; Crellin, Paul K; Coppel, Ross L; Andrews, Philip C

2014-10-27

Homo- and heteroleptic bismuth thiolato complexes have been synthesised and characterised from biologically relevant tetrazole-, imidazole-, thiadiazole- and thiazole-based heterocyclic thiones (thiols): 1-methyl-1H-tetrazole-5-thiol (1-MMTZ(H)); 4-methyl-4H-1,2,4-triazole-3-thiol (4-MTT(H)); 1-methyl-1H-imidazole-2-thiol (2-MMI(H)); 5-methyl-1,3,4-thiadiazole-2-thiol (5-MMTD(H)); 1,3,4-thiadiazole-2-dithiol (2,5-DMTD(H)2 ); and 4-(4-bromophenyl)thiazole-2-thiol (4-BrMTD(H)). Reaction of BiPh3 with 1-MMTZ(H) produced the rare Bi(V) thiolato complex [BiPh(1-MMTZ)4 ], which undergoes reduction in DMSO to give [BiPh(1-MMTZ)2 {(1-MMTZ(H)}2 ]. Reactions with PhBiCl2 or BiPh3 generally produced monophenylbismuth thiolates, [BiPh(SR)2 ]. The crystal structures of [BiPh(1-MMTZ)2 {1-MMTZ(H)}2 ], [BiPh(5-MMTD)2 ], [BiPh{2,5-DMTD(H)}2 (Me2 CO)] and [Bi(4-BrMTD)3 ] were obtained. Evaluation of the bactericidal properties against M. smegmatis, S. aureus, MRSA, VRE, E. faecalis and E. coli showed complexes containing the anionic ligands 1- MMTZ, 4-MTT and 4-BrMTD to be most effective. The dithiolato dithione complexes [BiPh(4-MTT)2 {4-MTT(H)}2 ] and [BiPh(1-MMTZ)2 {1-MMTZ(H)}2 ] were most effective against all the bacteria: MICs 0.34 μM for [BiPh(4-MTT)2 {4-MTT(H)}2 ] against VRE, and 1.33 μM for [BiPh(1-MMTZ)2 {1-MMTZ(H)}2 ] against M. smegmatis and S. aureus. Tris-thiolato Bi(III) complexes were least effective overall. All complexes showed little or no toxicity towards mammalian COS-7 cells at 20 μg mL(-1) . © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structural stability, vibrational, and bonding properties of potassium 1, 1'-dinitroamino-5, 5'-bistetrazolate: An emerging green primary explosive

NASA Astrophysics Data System (ADS)

Yedukondalu, N.; Vaitheeswaran, G.

2015-08-01

Potassium 1,1'-dinitroamino-5,5'-bistetrazolate (K2DNABT) is a nitrogen rich (50.3% by weight, K2C2N12O4) green primary explosive with high performance characteristics, namely, velocity of detonation (D = 8.33 km/s), detonation pressure (P = 31.7 GPa), and fast initiating power to replace existing toxic primaries. In the present work, we report density functional theory (DFT) calculations on structural, equation of state, vibrational spectra, electronic structure, and absorption spectra of K2DNABT. We have discussed the influence of weak dispersive interactions on structural and vibrational properties through the DFT-D2 method. We find anisotropic compressibility behavior (b

Tetrazole acetic acid: Tautomers, conformers, and isomerization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Araujo-Andrade, C.; Department of Chemistry, University of Coimbra, 3004-535 Coimbra; Reva, I., E-mail: reva@qui.uc.pt

2014-02-14

Monomers of (tetrazol-5-yl)-acetic acid (TAA) were obtained by sublimation of the crystalline compound and the resulting vapors were isolated in cryogenic nitrogen matrices at 13 K. The conformational and tautomeric composition of TAA in the matrix was characterized by infrared spectroscopy and vibrational calculations carried out at the B3LYP/6-311++G(d,p) level. TAA may adopt two tautomeric modifications, 1H- and 2H-, depending on the position of the annular hydrogen atom. Two-dimensional potential energy surfaces (PESs) of TAA were theoretically calculated at the MP2/6-311++G(d,p) level, for each tautomer. Four and six symmetry-unique minima were located on these PESs, for 1H- and 2H-TAA, respectively.more » The energetics of the detected minima was subsequently refined by calculations at the QCISD level. Two 1H- and three 2H-conformers fall within the 0–8 kJ mol{sup −1} energy range and should be appreciably populated at the sublimation temperature (∼330 K). Observation of only one conformer for each tautomer (1ccc and 2pcc) is explained in terms of calculated barriers to conformational rearrangements. All conformers with the cis O=COH moiety are separated by low barriers (less than 10 kJ mol{sup −1}) and collapse to the most stable 1ccc (1H-) and 2pcc (2H-) forms during deposition of the matrix. On the trans O=COH surfaces, the relative energies are very high (between 12 and 27 kJ mol{sup −1}). The trans forms are not thermally populated at the sublimation conditions and were not detected in matrices. One high-energy form in each tautomer, 1cct (1H-) and 2pct (2H-), was found to differ from the most stable form only by rotation of the OH group and separated from other forms by high barriers. This opened a perspective for their stabilization in a matrix. 1cct and 2pct were generated in the matrices selectively by means of narrow-band near-infrared (NIR) irradiations of the samples at 6920 and 6937 cm{sup −1}, where the first OH stretching overtone vibrations of 1ccc and 2pcc occur. The reverse transformations could be induced by irradiations at 7010 and 7030 cm{sup −1}, transforming 1cct and 2pct back to 1ccc and 2pcc, also selectively. Besides the NIR-induced transformations, the photogenerated 1cct and 2pct forms also decay in N{sub 2} matrices back to 1ccc and 2pcc spontaneously, with characteristic decay times of hours (1H) and tens of minutes (2H). The decay mechanism is rationalized in terms of the proton tunneling. In crystals, TAA exists exclusively as 1H-tautomer. By contrast, the tautomeric composition of the matrix-isolated monomers was found to consist of both 1H- and 2H-tautomers, in comparable amounts. A mechanistic discussion of the tautomerization process occurring during sublimation, accounting also for the observed minor decomposition of TAA leading to CO{sub 2} and 5-methyl-tetrazole, is proposed.« less

Derivatives of 1,5-diamino-1H-tetrazole: a new family of energetic heterocyclic-based salts.

PubMed

Gálvez-Ruiz, Juan Carlos; Holl, Gerhard; Karaghiosoff, Konstantin; Klapötke, Thomas M; Löhnwitz, Karolin; Mayer, Peter; Nöth, Heinrich; Polborn, Kurt; Rohbogner, Christoph J; Suter, Max; Weigand, Jan J

2005-06-13

1,5-Diamino-1H-tetrazole (2, DAT) can easily be protonated by reaction with strong mineral acids, yielding the poorly investigated 1,5-diaminotetrazolium nitrate (2a) and perchlorate (2b). A new synthesis for 2 is introduced that avoids lead azide as a hazardous byproduct. The reaction of 1,5-diamino-1H-tetrazole with iodomethane (7a) followed by the metathesis of the iodide (7a) with silver nitrate (7b), silver dinitramide (7c), or silver azide (7d) leads to a new family of heterocyclic-based salts. In all cases, stable salts were obtained and fully characterized by vibrational (IR, Raman) spectroscopy, multinuclear NMR spectroscopy, mass spectrometry, elemental analysis, X-ray structure determination, and initial safety testing (impact and friction sensitivity). Most of the salts exhibit good thermal stabilities, and both the perchlorate (2b) and the dinitramide (7c) have melting points well below 100 degrees C, yet high decomposition onsets, defining them as new (7c), highly energetic ionic liquids. Preliminary sensitivity testing of the crystalline compounds indicates rather low impact sensitivities for all compounds, the highest being that of the perchlorate (2b) and the dinitramide (7c) with a value of 7 J. In contrast, the friction sensitivities of the perchlorate (2b, 60 N) and the dinitramide (7c, 24 N) are relatively high. The enthalpies of combustion (Delta(c)H degrees ) of 7b-d were determined experimentally using oxygen bomb calorimetry: Delta(c)H degrees (7b) = -2456 cal g(-)(1), Delta(c)H degrees (7c) = -2135 cal g(-)(1), and Delta(c)H degrees (7d) = -3594 cal g(-)(1). The standard enthalpies of formation (Delta(f)H degrees ) of 7b-d were obtained on the basis of quantum chemical computations using the G2 (G3) method: Delta(f)H degrees (7b) = 41.7 (41.2) kcal mol(-)(1), Delta(f)H degrees (7c) = 92.1 (91.1) kcal mol(-)(1), and Delta(f)H degrees (7d) = 161.6 (161.5) kcal mol(-)(1). The detonation velocities (D) and detonation pressures (P) of 2b and 7b-d were calculated using the empirical equations of Kamlet and Jacobs: D(2b) = 8383 m s(-)(1), P(2b) = 32.2 GPa; D(7b) = 7682 m s(-)(1), P(7b) = 23.4 GPa; D(7c) = 8827 m s(-)(1), P(7c) = 33.6 GPa; and D(7d) = 7405 m s(-)(1), P(7d) = 20.8 GPa. For all compounds, a structure determination by single-crystal X-ray diffraction was performed. 2a and 2b crystallize in the monoclinic space groups C2/c and P2(1)/n, respectively. The salts of 7 crystallize in the orthorhombic space groups Pna2(1) (7a, 7d) and Fdd2 (7b). The hydrogen-bonded ring motifs are discussed in the formalism of graph-set analysis of hydrogen-bond patterns and compared in the case of 2a, 2b, and 7b.

78 FR 31840 - Safety Zone; USO Patriotic Festival Air Show, Atlantic Ocean; Virginia Beach, VA

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-28

...-AA00 Safety Zone; USO Patriotic Festival Air Show, Atlantic Ocean; Virginia Beach, VA AGENCY: Coast... provide for the safety of life on navigable waters during the USO Patriotic Festival Air Show. This action... Patriotic Festival Air Show, Atlantic Ocean; Virginia Beach, VA. (a) Regulated Area. The following area is a...

Ant and Mite Diversity Drives Toxin Variation in the Little Devil Poison Frog.

PubMed

McGugan, Jenna R; Byrd, Gary D; Roland, Alexandre B; Caty, Stephanie N; Kabir, Nisha; Tapia, Elicio E; Trauger, Sunia A; Coloma, Luis A; O'Connell, Lauren A

2016-06-01

Poison frogs sequester chemical defenses from arthropod prey, although the details of how arthropod diversity contributes to variation in poison frog toxins remains unclear. We characterized skin alkaloid profiles in the Little Devil poison frog, Oophaga sylvatica (Dendrobatidae), across three populations in northwestern Ecuador. Using gas chromatography/mass spectrometry, we identified histrionicotoxins, 3,5- and 5,8-disubstituted indolizidines, decahydroquinolines, and lehmizidines as the primary alkaloid toxins in these O. sylvatica populations. Frog skin alkaloid composition varied along a geographical gradient following population distribution in a principal component analysis. We also characterized diversity in arthropods isolated from frog stomach contents and confirmed that O. sylvatica specialize on ants and mites. To test the hypothesis that poison frog toxin variability reflects species and chemical diversity in arthropod prey, we (1) used sequencing of cytochrome oxidase 1 to identify individual prey specimens, and (2) used liquid chromatography/mass spectrometry to chemically profile consumed ants and mites. We identified 45 ants and 9 mites in frog stomachs, including several undescribed species. We also showed that chemical profiles of consumed ants and mites cluster by frog population, suggesting different frog populations have access to chemically distinct prey. Finally, by comparing chemical profiles of frog skin and isolated prey items, we traced the arthropod source of four poison frog alkaloids, including 3,5- and 5,8-disubstituted indolizidines and a lehmizidine alkaloid. Together, the data show that toxin variability in O. sylvatica reflects chemical diversity in arthropod prey.

Novel Cholinesterase Inhibitors Based on O-Aromatic N,N-Disubstituted Carbamates and Thiocarbamates.

PubMed

Krátký, Martin; Štěpánková, Šárka; Vorčáková, Katarína; Švarcová, Markéta; Vinšová, Jarmila

2016-02-11

Based on the presence of carbamoyl moiety, twenty salicylanilide N,N-disubstituted (thio)carbamates were investigated using Ellman's method for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). O-Aromatic (thio)carbamates exhibited weak to moderate inhibition of both cholinesterases with IC50 values within the range of 1.60 to 311.0 µM. IC50 values for BChE were mostly lower than those obtained for AChE; four derivatives showed distinct selectivity for BChE. All of the (thio)carbamates produced a stronger inhibition of AChE than rivastigmine, and five of them inhibited BChE more effectively than both established drugs rivastigmine and galantamine. In general, 5-chloro-2-hydroxy-N-[4-(trifluoromethyl)-phenyl]benzamide, 2-hydroxy-N-phenylbenzamide as well as N-methyl-N-phenyl carbamate derivatives led to the more potent inhibition. O-{4-Chloro-2-[(4-chlorophenyl)carbamoyl]phenyl} dimethylcarbamothioate was identified as the most effective AChE inhibitor (IC50 = 38.98 µM), while 2-(phenylcarbamoyl)phenyl diphenylcarbamate produced the lowest IC50 value for BChE (1.60 µM). Results from molecular docking studies suggest that carbamate compounds, especially N,N-diphenyl substituted representatives with considerable portion of aromatic moieties may work as non-covalent inhibitors displaying many interactions at peripheral anionic sites of both enzymes. Mild cytotoxicity for HepG2 cells and consequent satisfactory calculated selectivity indexes qualify several derivatives for further optimization.

Structure-activity relationships of 2, 4-disubstituted pyrimidines as dual ERα/VEGFR-2 ligands with anti-breast cancer activity.

PubMed

Luo, Guoshun; Tang, Zhichao; Lao, Kejing; Li, Xinyu; You, Qidong; Xiang, Hua

2018-04-25

Both ERα and VEGFR-2 are important targets for cancer therapies. Here a series of 2, 4-disubstituted pyrimidine derivatives were designed, synthesized and evaluated as dual ERα/VEGFR-2 ligands. Most of the derivatives exhibited potent activities in both enzymatic and cellular assays. Structure-activity relationship studies showed that a hydrogen-bonding interaction in the head section is important factors for the enhancement of ERα-binding affinity. The most potent compound II-9OH, an analog of 2-(4-hydroxylphenyl)pyrimidine, was 19-fold more efficacious than tamoxifen in MCF-7 cancer cells and exhibited the best ERα binding affinity (IC 50  = 1.64 μM) as well as excellent VEGFR-2 inhibition (IC 50  = 0.085 μM). Furthermore, this dual targeted compound II-9OH exerted significantly antiestrogenic property via suppressing the expression of progesterone receptor (PgR) mRNA in MCF-7 cells and also showed obvious in vivo angiogenesis inhibitory effects in CAM assay. An induction of apoptosis and a decrease in cell migration, accompanied by transduction inhibition of Raf-1/MAPK/ERK pathway, were observed in MCF-7 cells after treatment with II-9OH, suggesting that II-9OH is a promising candidate for the development of multifunctional agents targeting ERα and VEGFR-2 in the therapy of some breast cancers. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Functional disubstituted polyacetylenes: Synthesis, liquid crystallinity, light emission, and fluorescent photopatterning of biphenyl-containing poly(1-phenyl-octyne)s with different functional bridges.

PubMed

Lam, Jacky W Y; Qin, Anjun; Dong, Yuping; Lai, Lo Ming; Häussler, Matthias; Dong, Yongqiang; Tang, Ben Zhong

2006-11-02

Biphenyl (Biph)-containing 1-phenyl-1-octynes and their polymers are synthesized, and the effects of functional bridge groups on the mesomorphic and optical properties of the polymers are studied. The nonmesomorphic disubstituted acetylene monomers (C6H13)C[triple bond]C(C6H4)O(CH2)12O-Biph-OC7H15 (1), (C6H13)C[triple bond]C(C6H4)O(CH2)11OOC-Biph-OC7H15 (2), and (C6H13)C[triple bond]C(C6H4)CO2(CH2)12OOC-Biph-OC7H15 (3) are prepared by multistep reaction routes and converted into their corresponding polymers P1-P3 by a WCl6-Ph4Sn catalyst. The structures and properties of the polymers are characterized and evaluated by NMR, TGA, DSC, POM, XRD, UV, and PL analyses. The mesogenic pendants have endowed the polymers with high thermal stability (> or =400 degrees C). While P1 exhibits no liquid crystallinity, P2 and P3 form enantiotropic S(A) phase with a monolayer structure. Upon photoexcitation, the polymers emit blue and blue-green lights of 460 and 480 nm, respectively, in THF with quantum efficiencies larger than 30%. UV irradiation of a thin film of P2 through a mask oxidizes and quenches the light emission of the exposed regions, generating a two-dimensional luminescent photoimage.

Structural Basis of APH(3)-IIIa-Mediated Resistance to N1-Substituted Aminoglycoside Antibiotics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fong, D.; Berghuis, A

2009-01-01

Butirosin is unique among the naturally occurring aminoglycosides, having a substituted amino group at position 1 (N1) of the 2-deoxystreptamine ring with an (S)-4-amino-2-hydroxybutyrate (AHB) group. While bacterial resistance to aminoglycosides can be ascribed chiefly to drug inactivation by plasmid-encoded aminoglycoside-modifying enzymes, the presence of an AHB group protects the aminoglycoside from binding to many resistance enzymes, and hence, the antibiotic retains its bactericidal properties. Consequently, several semisynthetic N1-substituted aminoglycosides, such as amikacin, isepamicin, and netilmicin, were developed. Unfortunately, butirosin, amikacin, and isepamicin are not resistant to inactivation by 3'-aminoglycoside O-phosphotransferase type IIIa [APH(3')-IIIa]. We report here the crystal structuremore » of APH(3')-IIIa in complex with an ATP analog, AMPPNP [adenosine 5'-(?,{gamma}-imido)triphosphate], and butirosin A to 2.4-A resolution. The structure shows that butirosin A binds to the enzyme in a manner analogous to other 4,5-disubstituted aminoglycosides, and the flexible antibiotic-binding loop is key to the accommodation of structurally diverse substrates. Based on the crystal structure, we have also constructed a model of APH(3')-IIIa in complex with amikacin, a commonly used semisynthetic N1-substituted 4,6-disubstituted aminoglycoside. Together, these results suggest a strategy to further derivatize the AHB group in order to generate new aminoglycoside derivatives that can elude inactivation by resistance enzymes while maintaining their ability to bind to the ribosomal A site.« less

C-H bond functionalization via hydride transfer: formation of α-arylated piperidines and 1,2,3,4-tetrahydroisoquinolines via stereoselective intramolecular amination of benzylic C-H bonds.

PubMed

Vadola, Paul A; Carrera, Ignacio; Sames, Dalibor

2012-08-17

We here report a study of the intramolecular amination of sp(3) C-H bonds via the hydride transfer cyclization of N-tosylimines (HT-amination). In this transformation, 5-aryl aldehydes are subjected to N-toluenesulfonamide in the presence of BF(3)·OEt(2) to effect imine formation and HT-cyclization, leading to 2-arylpiperidines and 3-aryl-1,2,3,4-tetrahydroisoquinolines in a one-pot procedure. We examined the reactivity of a range of aldehyde substrates as a function of their conformational flexibility. Substrates of higher conformational rigidity were more reactive, giving higher yields of the desired products. However, a single substituent on the alkyl chain linking the N-tosylimine and the benzylic sp(3) C-H bonds was sufficient for HT-cyclization to occur. In addition, an examination of various arenes revealed that the electronic character of the hydridic C-H bonds dramatically affects the efficiency of the reaction. We also found that this transformation is highly stereoselective; 2-substituted aldehydes yield cis-2,5-disubstituted piperidines, while 3-substituted aldehydes afford trans-2,4-disubstituted piperidines. The stereoselectivity is a consequence of thermodynamic control. The pseudoallylic strain between the arene and tosyl group on the piperidine ring is proposed to rationalize the greater stability of the isomer with the aryl ring in the axial position. This preferential placement of the arene is proposed to affect the observed stereoselectivity.

A nonpeptidyl growth hormone secretagogue.

PubMed

Smith, R G; Cheng, K; Schoen, W R; Pong, S S; Hickey, G; Jacks, T; Butler, B; Chan, W W; Chaung, L Y; Judith, F

1993-06-11

A nonpeptidyl secretagogue for growth hormone of the structure 3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-([2'-(1H-tetrazol-5 -yl) (1,1'-biphenyl)-4-yl]methyl)-1H-1-benzazepin-3(R)-yl)-butanamid e (L-692,429) has been identified. L-692,429 synergizes with the natural growth hormone secretagogue growth hormone-releasing hormone and acts through an alternative signal transduction pathway. The mechanism of action of L-692,429 and studies with peptidyl and nonpeptidyl antagonists suggest that this molecule is a mimic of the growth hormone-releasing hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6). L-692,429 is an example of a nonpeptidyl specific secretagogue for growth hormone.

Chlorine-Free Red-Burning Pyrotechnics.

PubMed

Sabatini, Jesse J; Koch, Ernst-Christian; Poret, Jay C; Moretti, Jared D; Harbol, Seth M

2015-09-07

The development of a red, chlorine-free pyrotechnic illuminant of high luminosity and spectral purity was investigated. Red-light emission based solely on transient SrOH(g) has been achieved by using either 5-amino-1H-tetrazole or hexamine to deoxidize the combustion flame of a Mg/Sr(NO3 )2 /Epon-binder composition and reduce the amount of both condensed and gaseous SrO, which emits undesirable orange-red light. The new formulations were found to possess high thermal onset temperatures. Avoiding chlorine in these formulations eliminates the risk of the formation of PCBs, PCDDs, and PCDFs. This finding, hence, will have a great impact on both military pyrotechnics and commercial firework sectors. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Symposium on Explosives and Pyrotechnics, 13th, Hilton Head Island, SC, Dec. 2-4, 1986, Proceedings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1987-01-01

The present conference on explosive and pyrotechnic technologies discusses the shock-sensitivity of RDX, the thermodynamic properties of RDX, TNT, nitroglycerine, and HMX energetic molecules, the dynamic resistivity of exploding conductors, the decomposition of azides, the critical shock-initiation energy of emulsion explosives, actuator valve optimization, pyrotechnic aerosolization from novel imbibed liquid matrices, tetrazole initiators, and polymeric binders for red phosphorus pellets. Also discussed are channel-effect studies, the dynamic desensitization of coal mine explosives, the electromagnetic and electrostatic protection of explosives, the reliability of fuze explosive trains, the hazardous properties of explosive chemicals, the emulsification of an explosive with a chemical foamingmore » agent, and low energy ignition of HMX using a foil bridge.« less

Synthetic and Spectroscopic Studies on N-(i,j-Disubstituted Phenyl)-4- Substituted Benzenesulphonamides, 4-X'C6H4SO2NH(i,j-X2C6H3), where X' = H, CH3, C2H5, F, Cl or Br; i, j = 2, 3; 2, 4; 2, 5; 2, 6 or 3, 4; and X = CH3 or Cl

NASA Astrophysics Data System (ADS)

Shetty, Mahesha; Gowda, B. Thimme

2005-02-01

Fifty four N-(i,j-disubstituted phenyl)-4-substituted benzenesulphonamides of the general formula 4-X'C6H4SO2NH(i,j-X2C6H3), where X' = H, CH3, C2H5, F, Cl or Br; i,j = 2,3; 2,4; 2,5; 2,6 or 3, 4; and X = CH3 or Cl, are prepared and characterized and their infrared, 1H and 13C NMR spectra in solution are studied. The N-H stretching vibrations νN-H absorb in the range 3305 - 3205 cm-1, while the asymmetric and symmetric SO2 vibrations vary in the ranges 1377 - 1307 cm-1 and 1184 - 1128 cm-1, respectively. The N-(i,j-disubstituted phenyl)-4-substituted benzenesulphonamides show C-S, S-N and C-N stretching vibrations in the ranges 844 - 800 cm-1, 945 - 891 cm-1 and 1309 - 1170 cm-1, respectively. The compounds do not exhibit particular trends in the variation of these frequencies on substitution either at ortho or meta positions with either a methyl group or Cl. The observed 1H and 13C chemical shifts of are assigned to protons and carbon atoms of the two benzene rings. Incremental shifts of the ring protons and carbon atoms due to -SO2NH(i,j-X2C6H3) groups in C6H5SO2NH(i,j-X2C6H3) and 4-X'C6H4SO2NH- groups in 4-X'C6H4SO2NH(C6H*) are computed and employed to calculate the chemical shifts of the ring protons and carbon atoms in the substituted compounds 4-X'C6H4SO2NH(i,j-X2C6H3). The different methods of calculation lead to almost the same values in most cases and agree well with the observed chemical shifts, indicating the validity of the principle of additivity of the substituent effects with chemical shifts in these compounds.

Application of Chan-Lam cross coupling for the synthesis of N-heterocyclic carbene precursors bearing strong electron donating or withdrawing groups

NASA Astrophysics Data System (ADS)

Huang, Liliang; He, Chengxiang; Sun, Zhihua

2015-07-01

Chan-Lam cross coupling allowed efficient synthesis of N,N’-disubstituted ortho-phenylene diamines bearing strong electron donating or withdrawing groups, such as nitro or methoxy groups, with moderate to high yields. These diamines can then be turned into N-heterocyclic carbene precursors after condensation with trimethyl orthoformate. The same strategy can also be utilized for the synthesis of N-monosubstituted aniline derivatives containing a functionalized ortho-aminomethyl group as intermediates for chiral 6-membered ring carbene precursors.

Synthesis of heterocycles: Indolo (2,1-a) isoquinolines, renewables, and aptamer ligands for cellular imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beasley, Jonathan

2013-01-01

In this thesis, we explore both total syntheses and methodologies of several aromatic heterocyclic molecules. Extensions of the Kraus indole synthesis toward 2-substituted and 2,3-disubstituted indoles, as well as biologically attractive indolo[2,1-a]isoquinolines are described. Recent renewable efforts directed to commodity maleic acid and the first reported furan-based ionic liquids are described. Our total synthesis of mRNA aptamer ligand PDC-Gly, and its dye coupled forms, plus aminoglycoside dye coupled ligands used in molecular imaging, are described.

Ribosomal incorporation of backbone modified amino acids via an editing-deficient aminoacyl-tRNA synthetase.

PubMed

Iqbal, Emil S; Dods, Kara K; Hartman, Matthew C T

2018-02-14

The ability to incorporate non-canonical amino acids (ncAA) using translation offers researchers the ability to extend the functionality of proteins and peptides for many applications including synthetic biology, biophysical and structural studies, and discovery of novel ligands. Here we describe the high promiscuity of an editing-deficient valine-tRNA synthetase (ValRS T222P). Using this enzyme, we demonstrate ribosomal translation of 11 ncAAs including those with novel side chains, α,α-disubstitutions, and cyclic β-amino acids.

Discovery, synthesis, selectivity modulation and DMPK characterization of 5-azaspiro[2.4]heptanes as potent orexin receptor antagonists.

PubMed

Stasi, Luigi Piero; Artusi, Roberto; Bovino, Clara; Buzzi, Benedetta; Canciani, Luca; Caselli, Gianfranco; Colace, Fabrizio; Garofalo, Paolo; Giambuzzi, Silvia; Larger, Patrice; Letari, Ornella; Mandelli, Stefano; Perugini, Lorenzo; Pucci, Sabrina; Salvi, Matteo; Toro, PierLuigi

2013-05-01

Starting from a orexin 1 receptor selective antagonist 4,4-disubstituted piperidine series a novel potent 5-azaspiro[2.4]heptane dual orexin 1 and orexin 2 receptor antagonist class has been discovered. SAR and Pharmacokinetic optimization of this series is herein disclosed. Lead compound 15 exhibits potent activity against orexin 1 and orexin 2 receptors along with low cytochrome P450 inhibition potential, good brain penetration and oral bioavailability in rats. Copyright © 2013 Elsevier Ltd. All rights reserved.

Copper-free route to triazole-modified peptidomimetic by the combination of two multicomponent reactions in one pot.

PubMed

Niu, Teng-fei; Gu, Lin; Yi, Wen-bin; Cai, Chun

2012-05-14

An efficient copper-free protocol for the synthesis of 5-methyl-1H-1,2,3-triazole-modified peptidomimetics through the combination of Ugi four-component reaction with a three-component cycloaddition, has been developed. The copper-free straightforward process is suitable for drug discovery. The chemoselective preparation of 1,4-disubstituted, triazole-modified peptidomimetics by using alkynyl substituted amines may have potential biological and synthetic application. At last, a "Lapinski type" analysis of the physical properties was performed, which is expected to help drug discovery.

Trisphenalenyl-based neutral radical molecular conductor.

PubMed

Pal, Sushanta K; Itkis, Mikhail E; Tham, Fook S; Reed, Robert W; Oakley, Richard T; Haddon, Robert C

2008-03-26

We report the preparation, crystallization, and solid-state characterization of the first member of a new family of tris(1,9-disubstituted phenalenyl)silicon neutral radicals. In the solid state, the radical packs as weak partial pi-dimers with intermolecular carbon...carbon contacts that fall at the van der Waals atomic separation. Magnetic susceptibility measurements indicate approximately 0.7 Curie spins per molecule from room temperature down to 50 K, below which antiferromagnetic coupling becomes apparent; the compound has a room-temperature single-crystal conductivity of sigmaRT = 2.4 x 10(-6) S cm(-1).

Ketene reactions with tertiary amines.

PubMed

Allen, Annette D; Andraos, John; Tidwell, Thomas T; Vukovic, Sinisa

2014-01-17

Tertiary amines react rapidly and reversibly with arylketenes in acetonitrile forming observable zwitterions, and these undergo amine catalyzed dealkylation forming N,N-disubstituted amides. Reactions of N-methyldialkylamines show a strong preference for methyl group loss by displacement, as predicted by computational studies. Loss of ethyl groups in reactions with triethylamine also occur by displacement, but preferential loss of isopropyl groups in the phenylketene reaction with diisopropylethylamine evidently involves elimination. Quinuclidine rapidly forms long-lived zwitterions with arylketenes, providing a model for catalysis by cinchona and related alkaloids in stereoselective additions to ketenes.

Copper(II) Carboxylate Promoted Intramolecular Diamination of Terminal Alkenes: Improved Reaction Conditions and Expanded Substrate Scope

PubMed Central

Zabawa, Thomas P.

2008-01-01

The copper(II) carboxylate promoted diamination reaction has been improved by the use of the organic soluble copper(II) neodecanoate [Cu(ND)2]. Cu(ND)2 allowed the less polar solvent, dichloroethane (DCE) to be used, and as a consequence, decomposition of less reactive substrates could be avoided. High diastereoselectivity was observed in the synthesis of 2,5-disubstituted pyrrolidines. Ureas, bis(anilines) and α-amido pyrroles derived from 2-allylaniline could also participate in the diamination reaction. PMID:17447781

Copper-Catalyzed, Directing Group-Assisted Fluorination of Arene and Heteroarene C-H Bonds

PubMed Central

Truong, Thanh; Klimovica, Kristine; Daugulis, Olafs

2013-01-01

We have developed a method for direct, copper-catalyzed, auxiliary-assisted fluorination of β-sp2 C-H bonds of benzoic acid derivatives and γ-sp2 C-H bonds of α,α-disubstituted benzylamine derivatives. The reaction employs CuI catalyst, AgF fluoride source, and DMF, pyridine, or DMPU solvent at moderately elevated temperatures. Selective mono- or difluorination can be achieved by simply changing reaction conditions. The method shows excellent functional group tolerance and provides a straightforward way for the preparation of ortho-fluorinated benzoic acids. PMID:23758609

Enantioselective organocatalytic one-pot amination/aza-Michael/aldol condensation reaction sequence: synthesis of 3-pyrrolines with a quaternary stereocenter.

PubMed

Desmarchelier, Alaric; Coeffard, Vincent; Moreau, Xavier; Greck, Christine

2012-10-08

Primary amine-catalyzed direct conversion of α,α-disubstituted aldehydes into 3-pyrrolines with a quaternary stereocenter is reported. The one-pot enantioselective sequence is based on a α-amination, an aza-Michael addition of hydrazine, an aldol condensation dehydratation and proceeds with good yields and excellent levels of enantioselectivity. Synthetically attractive applications including the formation of aziridinopyrrolidine or epoxypyrrolidine derivatives with good yields and selectivities are also described. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polymerization of Enantiomerically Pure 2,3-Dicarboalkoxy Norbornadienes and 5,6-Disubstituted Norbornenes by Well-Characterized Molybdenum ROMP catalysts

DTIC Science & Technology

1993-10-29

menthol , R-(-)-pantalactone, BBr3 (IM in CH2C12), PhMe2SiCI and t-BuLi were purchased from Aldrich and used as received. Mo(CHCMe2Ph)(NAr)(O-t-Bu)2 was...2,3- (COCl)2norbornadiene1 9 (9.05 g, 41.7 mmol) in THF (50 mL) was added dropwise to a stirred THF (200 mL) solution of IR, 2S, 5R-(-)- menthol (14.33 g

Stereoselective Formation of Trisubstituted Vinyl Boronate Esters by the Acid-Mediated Elimination of α-Hydroxyboronate Esters

PubMed Central

2015-01-01

The copper-catalyzed diboration of ketones followed by an acid-catalyzed elimination leads to the formation of 1,1-disubstituted and trisubstituted vinyl boronate esters with moderate to good yields and selectivity. Addition of tosic acid to the crude diboration products provides the corresponding vinyl boronate esters upon elimination. The trisubstituted vinyl boronate esters are formed as the (Z)-olefin isomer, which was established by subjecting the products to a Suzuki–Miyaura coupling reaction to obtain alkenes of known geometry. PMID:24915498

Silicon-directed rhenium-catalyzed allylic carbaminations and oxidative fragmentations of γ-silyl allylic alcohols.

PubMed

Chavhan, Sanjay W; Cook, Matthew J

2014-04-22

A highly regioselective allylic substitution of β-silyl allylic alcohols has been achieved that provides the branched isomer as a single product. This high level of regiocontrol is achieved through the use of a vinyl silane group that can perform a Hiyama coupling providing 1,3-disubstituted allylic amines. An unusual oxidative fragmentation product was also observed at elevated temperature that appears to proceed by a Fleming-Tamao-type oxidation-elimination pathway. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lipid oxidation. Part 2. Oxidation products of olive oil methyl esters.

PubMed

Pokorný, J; Tài, P; Parízková, H; Smidrkalová, E; El-Tarras, M F; Janícek, G

1976-01-01

Olive oil was converted into methyl esters which were autoxidized at 60 degrees C. The composition of oxidized products was determined by the comparison of infrared spectra and NMR spectra of the original and acetylated samples, the sample reduced with potassium iodide and the acetylated reduced sample. Oxidized products were separated by preparative thin layer chromatography on silica gel and characterized by selective detection and by infrared spectrometry of the fractions. The oxidation products consisted of hydroperoxido butyl oleate, substituted hydroperoxides, mono- and disubstituted monomeric derivatives and a small amount of oligomers.

Application of 2-cyanoethyl N,N,N',N'-tetraisopropylphosphorodiamidite for in situ preparation of deoxyribonucleoside phosphoramidites and their use in polymer-supported synthesis of oligodeoxyribonucleotides.

PubMed Central

Nielsen, J; Taagaard, M; Marugg, J E; van Boom, J H; Dahl, O

1986-01-01

Deoxyribonucleoside phosphoramidites are prepared in situ from 5'-O,N-protected deoxyribonucleosides and 2-cyanoethyl N,N,N',N'-tetraisopropylphosphorodiamidite with tetrazole as catalyst, and the solutions applied directly on an automatic solid-phase DNA synthesizer. Using LCAA-CPG support and a cycle time of 12.5 min, oligonucleotides of 16-25 bases are obtained with a DMT-efficiency per cycle of 98.0-99.3%. The crude and fully deblocked products are of a purity comparable to that obtained using purified phosphoramidites. In case of d(G)16 the product was difficult to analyse and a better product was not obtained using doubly protected (O-6 diphenylcarbamoyl) guanine. PMID:3763407

Pentazadiene: a high-nitrogen linkage in energetic materials.

PubMed

Wang, Qi; Pang, Fuqing; Wang, Guilong; Huang, Jinglun; Nie, Fude; Chen, Fu-Xue

2017-02-16

A novel N 5 -linear energetic moiety of pentazadiene has been constructed for the first time from a triazene precursor. Thus, a series of 1,3,5-tri(tetrazol-5-yl)pentaza-1,4-dienes have been synthesized in moderate to high yields by treatment of 1,3-bis(tetr-azol-5-yl)triazenes with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) under mild conditions. All compounds were fully characterized using IR spectroscopy, 1 H and 13 C NMR spectroscopy, HRMS, and differential scanning calorimetry (DSC), and, in the case of 1,3,5-tri(2-methyltetrazol-5-yl)pentaza-1,4-diene (2a) together with single crystal X-ray structuring and 15 N NMR spectroscopy. Calculations predict that 2a has a heat of formation of 1699.2 kJ mol -1 .

Isolation of compound and CNS depressant activities of Mikania scandens Willd with special emphasis to brain biogenic amines in mice.

PubMed

Pal, Dilipkumar; Mazumder, Upal Kanti

2014-12-01

Mikania scandens, a twining herb that grows as a weed in India and Bangladesh is used as vegetables and is a good source of vitamin A, C, B complex, mikanin, sesquiterpenes, betasitosterin, stigmasterol and friedelin. The present communication reports CNS depressant activities with special emphasis to brain biogenic amines in mice. Ethanol extract of leaves of M. scandens (EEMS) was prepared by Soxhalation and analyzed chemically. EEMS potentiated sleeping time induced by pentobarbitone, diazepam and meprobamate and showed significant reduction in the number of writhes and stretches. EEMS caused significant protection against pentylene tetrazole-induced convulsion and increased catecholamines and brain amino acids level significantly. Results showed that EEMS produced good CNS depressant effects in mice.

New Imidazole-based High Nitrogen Energetic Materials

NASA Astrophysics Data System (ADS)

Windler, G. Kenneth; Leonard, Philip; Schulze, Maxwell; Hartline, Ernest

2017-06-01

Energetic materials derive their power from energy release, usually in the form of gaseous products. The type and quantity of these products contribute to performance and detonation parameters. In particular, high-nitrogen materials produce large quantities of elemental nitrogen, and can be tuned via molecular structure for suitability as propellants (gas generators) or explosives. In this work, the five-membered nitrogen heterocycle imidazole is used as a substrate for a variety of high-nitrogen materials. Substitution of the imidazole ring directly with nitro-, azido-, diazo-, and tetrazole moieties allows for tunable properties of the resultant energetic material. Properties can be further tailored by salt formation at the acidic proton(s) on the molecules. The various combinations of these derivatives are presented, along with the substitution effects on physical, chemical, and explosive properties.

Ruthenium Catalyzed Diastereo- and Enantioselective Coupling of Propargyl Ethers with Alcohols: Siloxy-Crotylation via Hydride Shift Enabled Conversion of Alkynes to π-Allyls

PubMed Central

Liang, Tao; Zhang, Wandi; Chen, Te-Yu; Nguyen, Khoa D.; Krische, Michael J.

2015-01-01

The first enantioselective carbonyl crotylations through direct use of alkynes as chiral allylmetal equivalents are described. Chiral ruthenium(II) complexes modified by Josiphos (SL-J009-1) catalyze the C-C coupling of TIPS-protected propargyl ether 1a with primary alcohols 2a-2o to form products of carbonyl siloxy-crotylation 3a-3o, which upon silyl deprotection-reduction deliver 1,4-diols 5a-5o with excellent control of regio-, anti-diastereo- and enantioselectivity. Structurally related propargyl ethers 1b and 1c bearing ethyl- and phenyl-substituents engage in diastereo- and enantioselective coupling, as illustrated in the formation of adducts 5p and 5q, respectively. Selective mono-tosylation of diols 5a, 5c, 5e, 5f, 5k and 5m is accompanied by spontaneous cyclization to deliver the trans-2,3-disubstituted furans 6a, 6c, 6e, 6f, 6k and 6m, respectively. Primary alcohols 2a, 2l and 2p were converted to the siloxy-crotylation products 3a, 3l and 3p, which upon silyl deprotection-lactol oxidation were transformed to the trans-4,5-disubstituted γ-butyrolactones 7a, 7l and 7p. The formation of 7p represents a total synthesis of (+)-trans-whisky lactone. Unlike closely related ruthenium catalyzed alkyne-alcohol C-C couplings, deuterium labeling studies provide clear evidence of a novel 1,2-hydride shift mechanism that converts metal-bound alkynes to π-allyls in the absence of intervening allenes. PMID:26418572

Synthesis of axially disubstituted silicon phthalocyanines and investigation of photodynamic effects on HCT-116 colorectal cancer cell line.

PubMed

Sarı, Ceren; Eyüpoğlu, Figen Celep; Değirmencioğlu, İsmail; Bayrak, Rıza

2018-05-15

Photodynamic therapy is one of the hot topics in cancer studies recently. Basically, photosensitizing chemical substrates which are stimulated by light having a specific wavelength cause fatal effect on different kind of cells in photodynamic therapy. In this study, axially 4-{[(1E)-2-furylmethylene]amino}phenol, 4-{[(1E)-2-thienylmethylene]amino}phenol and 4-{[(1E)-(4-nitro-2-thienyl)methylene]amino}phenol disubstituted silicon phthalocyanines were synthesized as Photosensitizers for photodynamic therapy in cancer treatment for the first time. The structural characterizations of these novel compounds were performed by a combination of FT-IR, 1 H-NMR, UV-vis and mass. All these newly prepared compounds did not show aggregation at the concentration range of 2 × 10 -6 -12 × 10 -6 M in tetrahydrofurane and also did not show aggregation in different organic solvents at 2 × 10 -6 M concentration. Phthalocyanines which are synthesized in this study are tested on HCT-116 colorectal cancer cells and stimulated by light has wavelength of 680 nm. The toxic effects on cancer cells which are caused by different concentrations of photosensitizing molecules have been examined and compared with the toxic effects on cancer cells that were kept in the dark. It is confirmed that these molecules caused toxic effects on colorectal cancer cells when they were stimulated by light but there was no toxic effect in the dark. Copyright © 2018. Published by Elsevier B.V.

Design and synthesis of novel HDAC8 inhibitory 2,5-disubstituted-1,3,4-oxadiazoles containing glycine and alanine hybrids with anti cancer activity.

PubMed

Pidugu, Vijaya Rao; Yarla, Nagendra Sastry; Pedada, Srinivasa Rao; Kalle, Arunasree M; Satya, A Krishna

2016-11-01

Oxadiazole is a heterocyclic compound containing an oxygen atom and two nitrogen atoms in a five-membered ring. Of the four oxadiazoles known, 1,3,4-oxadiazole has become an important structural motif for the development of new drugs and the compounds containing 1,3,4-oxadiazole cores have a broad spectrum of biological activity. Herein, we describe the design, synthesis and biological evaluation of a series of novel 2,5-disubstituted 1,3,4-oxadiazoles (10a-10j) as class I histone deacetylase (HDAC) inhibitors. The compounds were designed and evaluated for HDAC8 selectivity using in silico docking software (Glide) and the top 10 compounds with high dock score and obeying Lipinski's rule were synthesized organically. Further the biological HDAC inhibitory and selectivity assays and anti-proliferative assays were carried out. In in silico and in vitro studies, all compounds (10a-10j) showed significant HDAC inhibition and exhibited HDAC8 selectivity. Among all tested compounds, 10b showed substantial HDAC8 inhibitory activity and better anticancer activity which is comparable to the positive control, a FDA approved drug, vorinostat (SAHA). Structural activity relation is discussed with various substitutions in the benzene ring connected on 1,3,4-oxadizole and glycine/alanine. The study warranted further investigations to develop HDAC8-selective inhibitory molecule as a drug for neoplastic diseases. Novel 1,3,4-oxadizole substituted with glycine/alanine showed HDAC8 inhibition. Copyright © 2016 Elsevier Ltd. All rights reserved.

3-{(E)-[4-(4-Hy-droxy-3-meth-oxy-phen-yl)butan-2-yl-idene]amino}-1-phenyl-urea: crystal structure and Hirshfeld surface analysis.

PubMed

Tan, Ming Yueh; Crouse, Karen A; Ravoof, Thahira B S A; Jotani, Mukesh M; Tiekink, Edward R T

2018-01-01

Two independent mol-ecules ( A and B ) comprise the asymmetric unit of the title compound, C 18 H 21 N 3 O 3 . The urea moiety is disubstituted with one amine being linked to a phenyl ring, which is twisted out of the plane of the CN 2 O urea core [dihedral angles = 25.57 (11) ( A ) and 29.13 (10)° ( B )]. The second amine is connected to an imine ( E conformation), which is linked in turn to an ethane bridge that links a disubstituted benzene ring. Intra-molecular amine-N-H⋯N(imine) and hydroxyl-O-H⋯O(meth-oxy) hydrogen bonds close S (5) loops in each case. The mol-ecules have twisted conformations with the dihedral angles between the outer rings being 38.64 (81) ( A ) and 48.55 (7)° ( B ). In the crystal, amide-N-H⋯O(amide) hydrogen bonds link the mol-ecules A and B via an eight-membered {⋯HNCO} 2 synthon. Further associations between mol-ecules, leading to supra-molecular layers in the ac plane, are hydrogen bonds of the type hydroxyl-O-H⋯N(imine) and phenyl-amine-N-H⋯O(meth-oxy). Connections between layers, leading to a three-dimensional architecture, comprise benzene-C-H⋯O(hy-droxy) inter-actions. A detailed analysis of the calculated Hirshfeld surfaces shows mol-ecules A and B participate in very similar inter-molecular inter-actions and that any variations relate to conformational differences between the mol-ecules.

A Broadly Applicable NHC–Cu-Catalyzed Approach for Efficient, Site-, and Enantioselective Coupling of Readily Accessible (Pinacolato)alkenylboron Compounds to Allylic Phosphates and Applications to Natural Product Synthesis

PubMed Central

2015-01-01

A set of protocols for catalytic enantioselective allylic substitution (EAS) reactions that allow for additions of alkenyl units to readily accessible allylic electrophiles is disclosed. Transformations afford 1,4-dienes that contain a tertiary carbon stereogenic site and are promoted by 1.0–5.0 mol % of a copper complex of an N-heterocyclic carbene (NHC). Aryl- as well as alkyl-substituted electrophiles bearing a di- or trisubstituted alkene may be employed. Reactions can involve a variety of robust alkenyl–(pinacolatoboron) [alkenyl–B(pin)] compounds that can be either purchased or prepared by various efficient, site-, and/or stereoselective catalytic reactions, such as cross-metathesis or proto-boryl additions to terminal alkynes. Vinyl-, E-, or Z-disubstituted alkenyl-, 1,1-disubstituted alkenyl-, acyclic, or heterocyclic trisubstituted alkenyl groups may be added in up to >98% yield, >98:2 SN2′:SN2, and 99:1 enantiomeric ratio (er). NHC–Cu-catalyzed EAS with alkenyl–B(pin) reagents containing a conjugated carboxylic ester or aldehyde group proceed to provide the desired 1,4-diene products in good yield and with high enantioselectivity despite the presence of a sensitive stereogenic tertiary carbon center that could be considered prone to epimerization. In most instances, the alternative approach of utilizing an alkenylmetal reagent (e.g., an Al-based species) represents an incompatible option. The utility of the approach is illustrated through applications to enantioselective synthesis of natural products such as santolina alcohol, semburin, nyasol, heliespirone A, and heliannuol E. PMID:24467274

A broadly applicable NHC-Cu-catalyzed approach for efficient, site-, and enantioselective coupling of readily accessible (pinacolato)alkenylboron compounds to allylic phosphates and applications to natural product synthesis.

PubMed

Gao, Fang; Carr, James L; Hoveyda, Amir H

2014-02-05

A set of protocols for catalytic enantioselective allylic substitution (EAS) reactions that allow for additions of alkenyl units to readily accessible allylic electrophiles is disclosed. Transformations afford 1,4-dienes that contain a tertiary carbon stereogenic site and are promoted by 1.0-5.0 mol % of a copper complex of an N-heterocyclic carbene (NHC). Aryl- as well as alkyl-substituted electrophiles bearing a di- or trisubstituted alkene may be employed. Reactions can involve a variety of robust alkenyl-(pinacolatoboron) [alkenyl-B(pin)] compounds that can be either purchased or prepared by various efficient, site-, and/or stereoselective catalytic reactions, such as cross-metathesis or proto-boryl additions to terminal alkynes. Vinyl-, E-, or Z-disubstituted alkenyl-, 1,1-disubstituted alkenyl-, acyclic, or heterocyclic trisubstituted alkenyl groups may be added in up to >98% yield, >98:2 SN2':SN2, and 99:1 enantiomeric ratio (er). NHC-Cu-catalyzed EAS with alkenyl-B(pin) reagents containing a conjugated carboxylic ester or aldehyde group proceed to provide the desired 1,4-diene products in good yield and with high enantioselectivity despite the presence of a sensitive stereogenic tertiary carbon center that could be considered prone to epimerization. In most instances, the alternative approach of utilizing an alkenylmetal reagent (e.g., an Al-based species) represents an incompatible option. The utility of the approach is illustrated through applications to enantioselective synthesis of natural products such as santolina alcohol, semburin, nyasol, heliespirone A, and heliannuol E.

C-H Bond Functionalization via Hydride Transfer: Formation of α-Arylated Piperidines and 1,2,3,4-Tetrahydroisoquinolines via Stereoselective Intramolecular Amination of Benzylic C-H Bonds

PubMed Central

Vadola, Paul A.; Carrera, Ignacio; Sames, Dalibor

2012-01-01

We here report a study of the intramolecular amination of sp3 C-H bonds via the hydride transfer cyclization of N-tosylimines (HT-amination). In this transformation, 5-aryl-aldehydes are subjected to N-toluenesulfonamide in the presence of BF3•OEt2 to effect imine formation and HT-cyclization, leading to 2-aryl-piperidines and 3-aryl-1,2,3,4-tetrahydroisoquinolines in a one-pot procedure. We examined the reactivity of a range of aldehyde substrates as a function of their conformational flexibility. Substrates of higher conformational rigidity were more reactive, giving higher yields of the desired products. However, a single substituent on the alkyl chain linking the N-tosylimine and the benzylic sp3 C-H bonds was sufficient for HT-cyclization to occur. In addition, an examination of various arenes revealed that the electronic character of the hydridic C-H bonds dramatically affects the efficiency of the reaction. We also found that this transformation is highly stereoselective; 2-substituted aldehydes yield cis-2,5-disubstituted piperidines, while 3-substituted aldehydes afford trans-2,4-disubstituted piperidines. The stereoselectivity is a consequence of thermodynamic control. The pseudo-allylic strain between the arene and tosyl group on the piperidine ring is proposed to rationalize the greater stability of the isomer with the aryl ring in the axial position. This preferential placement of the arene is proposed to affect the observed stereoselectivity. PMID:22672002

Study of magnetization switching for MRAM based memory technologies

NASA Astrophysics Data System (ADS)

Pham, Huy

Amphibian alkaloids are attractive targets for synthesis due to their biological activity. An important class of amphibian alkaloids is the 2,5-disubstituted pyrrolidine-based family of compounds. There are many synthetic approaches for the preparation of the trans-2,5-disubstituted pyrrolidines, but methods for the construction of the cis-2,5-pyrrolidines are limited. Therefore, it was desired to develop an enantioselective approach for the preparation of cis-2,5-disubsituted pyrrolidines. (+)-Tropin-2-one derived from cocaine was used as starting material to exploit the inherent stereochemistry for construction of the cis-pyrrolidine ring. This permitted the unequivocal assignment of the absolute configuration of the target pyrrolidine. The structurally simple pyrrolidine alkaloid, 225H, was selected as a target to develop a general synthetic approach. The enantioselective synthesis of 225H was achieved in nine steps and good overall yield. The search for potent cannabinoid receptor partial agonist ligands as potential marijuana addiction therapeutic agents has led to an investigation of the synthesis of diaryl ether hybrid analogues of BAY 59-3074. A series of 2-(3-alkyl-5-hydroxyphenoxy)-6-(trifluoromethyl)benzonitriles, 3-(2-cyano-3-(trifluoromethyl)phenoxy)phenylalkanoates, and (3-(benzyloxy)phenoxy)-6-(trifluoromethyl)benzonitriles were synthesized and evaluated in vitro for CB1 affinity. The olivetol diaryl ether analogue was the most potent ligand of the alkyl series, but the diaryl ester analogues exhibited modest affinity for CB1 receptors. The most potent compound of the series was the 2-(3-(benzyloxy)phenoxy)-6-(trifluoromethyl)benzonitrile. Keywords. amphibian alkaloids, enantioselective synthesis, pyrrolidine, cannabinoid receptor, marijuana.

Actitudes de los candidatos y maestros de ciencias en servicio acerca del uso de las herramientas computadorizadas en las clases de ciencias

NASA Astrophysics Data System (ADS)

Bayuelo, Ezequiel

Este estudio examino y comparo las actitudes de los candidatos a maestros de ciencias y los maestros de ciencias en servicio acerca de la utilizacion de las herramientas computadorizadas en las clases de ciencias. Tambien identifico y diferencio el uso que ellos dan a estas herramientas en las clases de ciencias. Este estudio presenta un diseno descriptivo exploratorio. Constituyeron la muestra trescientos diez sujetos que fueron candidatos a maestros de ciencias o maestros de ciencias en servicio. Para recoger los datos se construyo y valido un cuestionario de treinta y un itemes. Se utilizaron las pruebas estadisticas no parametricas Kruskal Wallis y Chi-cuadrado (test de homogeneidad) para establecer las diferencias entre las actitudes de los sujetos con relacion al uso de las herramientas computadorizadas en las clases de ciencias. Los hallazgos evidenciaron que son positivas y muy parecidas las actitudes de los candidatos a maestros y maestros en servicio hacia el uso de las herramientas computadorizadas. No hubo diferencias entre los candidatos y maestros en servicio en terminos de las actitudes de confianza y empatia hacia el uso de las herramientas computadorizadas en las clases de ciencias. En aspectos como el uso del banco de datos bibliografico Eric y el uso de las herramientas computadorizadas en actividades educativas como explorar conceptos, conceptuar, aplicar lo aprendido y hacer asignaciones hubo diferencias estadisticamente significativas entre los candidatos y los maestros en servicio. Al comparar las frecuencias observadas con las esperadas hubo mas maestros en servicio y menos candidatos que indicaron usar el anterior banco de datos y las herramientas computadorizadas en las mencionadas actividades educativas.

A Comparison of Ulnar Shortening Osteotomy Alone Versus Combined Arthroscopic Triangular Fibrocartilage Complex Debridement and Ulnar Shortening Osteotomy for Ulnar Impaction Syndrome

PubMed Central

Song, Hyun Seok

2011-01-01

Background This study compared the results of patients treated for ulnar impaction syndrome using an ulnar shortening osteotomy (USO) alone with those treated with combined arthroscopic debridement and USO. Methods The results of 27 wrists were reviewed retrospectively. They were divided into three groups: group A (USO alone, 10 cases), group B (combined arthroscopic debridement and USO, 9 cases), and group C (arthroscopic triangular fibrocartilage complex [TFCC] debridement alone, 8 cases). The wrist function was evaluated using the modified Mayo wrist score, disabilities of the arm, shoulder and hand (DASH) score and Chun and Palmer grading system. Results The modified Mayo wrist score in groups A, B, and C was 74.5 ± 8.9, 73.9 ± 11.6, and 61.3 ± 10.2, respectively (p < 0.05). The DASH score in groups A, B, and C was 15.6 ± 11.8, 19.3 ± 11.9, and 33.2 ± 8.5, respectively (p < 0.05). The average Chun and Palmer grading score in groups A and B was 85.7 ± 8.9 and 84.7 ± 6.7, respectively. The difference in the Mayo wrist score, DASH score and Chun and Palmer grading score between group A and B was not significant (p > 0.05). Conclusions Both USO alone and combined arthroscopic TFCC debridement with USO improved the wrist function and reduced the level of pain in the patients treated for ulnar impaction syndrome. USO alone may be the preferred method of treatment in patients if the torn flap of TFCC is not unstable. PMID:21909465

Enhancing the Art of Space Operations - Progress in JHU/APL Ultra-Stable Oscillator Capabilities

DTIC Science & Technology

2008-12-01

solution for robust extraterrestrial clocks with an operational life requirement greater than 10 years. Disciplined USO systems could be placed in very...USO) has been demonstrated in nearly 50 years of space applications to be a strategic asset to the space timekeeping and signal technologies of the...while also providing flight USO hardware to missions such as the NASA Gravity Recovery and Climate Experiment (GRACE) and JHU/APL’s New Horizons

Validation of Universal Scale in Oral Surgery (USOS) for Patient's Psycho-emotional Status Rating.

PubMed

Astramskaite, Inesa; Pinchasov, Ginnady; Gervickas, Albinas; Sakavicius, Dalius; Juodzbalys, Gintaras

2017-01-01

There aren't any objective methods that may help in standard evaluation of oral surgery patient's psycho-emotional status. Without any standardized evaluation, two main problems appear: heterogeneity between studies and ineffective patient's evaluation. Therefore, Universal Scale in Oral Surgery (USOS) for patient's psycho-emotional status rating has previously been proposed by authors. The aim of present study is to assess the clinical effectivity and validate the Universal Scale in Oral Surgery in case of outpatient tooth extraction for adult healthy patients. Clinical trial to validate the USOS for patient's psycho-emotional status rating was performed. In total 90 patients, that came for outpatient dental extraction to Lithuanian University of Health Sciences Oral and Maxillofacial Surgery Department ambulatory, were enrolled in clinical trial. Patients filled self-reported questionnaires before the procedure. Operating surgeon rated USOS for patient's psycho-emotional status rating doctor's part questionnaire after the procedure. 4 - 6 weeks later all patients were asked to fill USOS for patient's psycho-emotional status rating questionnaire retrospectively. According to the statistical analysis, the final composition of USOS for patient's psycho-emotional status rating that would fit to reliability coefficient should be composed from 6 patient part questions and 3 general doctor part questions. Universal Scale in Oral Surgery for patient's psycho-emotional status rating is a novel, doctor and patient rated scale which is suitable for clinical and scientific usage.

Oncologic and reproductive outcomes of cystectomy compared with oophorectomy as a treatment for borderline ovarian tumours.

PubMed

Song, Taejong; Hun Choi, Chel; Lee, Yoo-Young; Kim, Tae-Joong; Lee, Jeong-Won; Bae, Duk-Soo; Kim, Byoung-Gie

2011-08-01

The aim of this study was to compare the oncologic and reproductive outcomes of patients with borderline ovarian tumours (BOTs) who were treated with cystectomy or unilateral salpingo-oophorectomy (USO). The medical records of patients with BOTs who were treated between 1997 and 2009 were reviewed retrospectively. The recurrence rates were compared between the USO and cystectomy groups. The reproductive outcomes were assessed by telephone interviews. Patients with BOTs underwent a USO (n= 117) or cystectomy (n= 38). There were 12 patients who had recurrences: 1 patient had an invasive recurrence and 11 had borderline recurrences. The recurrence rate in the USO group (6.0%) was lower than in the cystectomy group (13.2%); however, this difference was not statistically significant (P= 0.110). All of the patients with recurrences were successfully treated with surgery and there was no clinical evidence of disease. Of the 116 patients contacted by telephone, 113 (97.4%) resumed menstruation following the surgery, and 45 of the 52 patients (86.5%) who attempted to conceive had successful pregnancies. USO (89.2%), like cystectomy (85.7%), resulted in excellent pregnancy rates for patients with BOTs. A USO is an appropriate treatment for women with BOTs who wish to preserve fertility. However, a cystectomy is a satisfactory fertility-sparing therapy when a cystectomy is the only surgical option.

Synthesis, Chemical and Physical Characterization of TKX-50

NASA Astrophysics Data System (ADS)

Klapoetke, Thomas

2015-06-01

TKX-50 (bis(hydroxylammonium) 5,5'-bis(tetrazolate-1 N-oxide)) is one of the most promising ionic salts as a possible replacement for RDX. The thermal behavior of TKX-50 (bis(hydroxylammonium) 5,5'-(tetrazolate-1 N-oxide)) and the kinetics of its thermal decomposition were studied using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The calculated results of the detonation parameters and equations of state for the detonation products (EOS DP) of explosive materials TKX-50 and MAD-X1 and several of their derivatives were obtained using the computer program EXPLO5 V.6.01. These values were also calculated for standard explosive materials which are commonly used such as TNT, PETN, RDX, HMX as well as for the more powerful explosive material CL-20 to allow comparisons to be made. The determination of the detonation parameters and EOS DP was conducted both for explosive materials having the maximum crystalline density and for porous right up to 50% in volume materials. The influence of the content of plastic binder polyisobutylene used (up to 20% in volume) on all of the investigated properties was also examined. Calculated results on shock wave loading of different inert barriers in a wide range of their dynamic properties under explosion on their surfaces of concrete size charges of different explosive materials in various initial states were obtained with the use of the one-dimensional computer hydrocode EP. Barriers due to materials such as polystyrene, textolite, magnesium, aluminum, zinc, copper, tantalum or tungsten were examined (Fig. 1). Initial values of pressure and other parameters of loading on the interface explosive-barrier were determined in the process of conducted calculations. Phenomena of propagation and attenuation of shock waves in barrier materials were considered too for all possible situations. From these calculations, an essentially complete overview of the explosion properties and characteristics of shock wave action onto barriers was obtained for several new and also for several standard explosive materials as a comparison. Work done in collaboration with Golubev/Fischer/Stierstorfer/Bohanek/Dobrilovic.

Aspirin and probenecid inhibit organic anion transporter 3-mediated renal uptake of cilostazol and probenecid induces metabolism of cilostazol in the rat.

PubMed

Wang, Chong; Wang, Changyuan; Liu, Qi; Meng, Qiang; Cang, Jian; Sun, Huijun; Peng, Jinyong; Ma, Xiaochi; Huo, Xiaokui; Liu, Kexin

2014-06-01

This study aimed to evaluate the transporter-mediated renal excretion mechanism for cilostazol and to characterize the mechanism of drug-drug interaction (DDI) between cilostazol and aspirin or probenecid. Concentrations of cilostazol and its metabolites OPC-13015 [6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-2(1H)-quinolinone] and OPC-13213 [3,4-dihydro-6-[4-[1-(trans-4-hydroxycyclohexyl)-1H-tetrazol-5-yl]butoxy]-2-(1H)-quinolinone] in rat biologic or cell samples were measured by liquid chromatography-tandem mass spectrometry. Coadministration with probenecid, benzylpenicillin, or aspirin decreased the cumulative urinary excretion of cilostazol and renal clearance. Concentrations of cilostazol and OPC-13213 in plasma decreased, and the concentration of OPC-13015 increased in the presence of probenecid. By contrast, rat plasma cilostazol, in combination with benzylpenicillin or aspirin, sharply increased, and concentrations of OPC-13015 and OPC-13213 did not change. In urine, OPC-13015 was below the level of detection. The cumulative urinary excretion of OPC-13213 decreased in the presence of probenecid, benzylpenicillin, or aspirin. Cilostazol was distributed in the kidney and liver, with tissue to plasma partition coefficient (Kp) values of 8.4 ml/g and 16.3 ml/g, respectively. Probenecid and aspirin reduced cilostazol distribution in the kidney. Probenecid did not affect cilostazol metabolism in the kidney but increased cilostazol metabolism in the liver, and aspirin had no effect on cilostazol metabolism. Benzylpenicillin, aspirin, and cyclo-trans-4-l-hydroxyprolyl-l-serine (JBP485) reduced cilostazol uptake in kidney slices and human organic anion transporter 3 (hOAT3)-human embryonic kidney 293 (HEK293) cells, whereas p-aminohippuric acid did not. Compared with the vector, hOAT3-HEK293 cells accumulated more cilostazol, whereas hOAT1-HEK293 cells did not. OAT3 and Oat3 play a major role in cilostazol renal excretion, whereas OAT1 and Oat1 do not. Oat3 and Cyp3a are both targets of the DDI between cilostazol and probenecid. Aspirin inhibits OAT3-mediated uptake of cilostazol and does not influence cilostazol metabolism.

Fragment-Based Optimization of Small Molecule CXCL12 Inhibitors for Antagonizing the CXCL12/CXCR4 Interaction

PubMed Central

Ziarek, Joshua J.; Liu, Yan; Smith, Emmanuel; Zhang, Guolin; Peterson, Francis C.; Chen, Jun; Yu, Yongping; Chen, Yu; Volkman, Brian F.; Li, Rongshi

2013-01-01

The chemokine CXCL12 and its G protein-coupled receptor (GPCR) CXCR4 are high-priority clinical targets because of their involvement in metastatic cancers (also implicated in autoimmune disease and cardiovascular disease). Because chemokines interact with two distinct sites to bind and activate their receptors, both the GPCRs and chemokines are potential targets for small molecule inhibition. A number of chemokines have been validated as targets for drug development, but virtually all drug discovery efforts focus on the GPCRs. However, all CXCR4 receptor antagonists with the exception of MSX-122 have failed in clinical trials due to unmanageable toxicities, emphasizing the need for alternative strategies to interfere with CXCL12/CXCR4-guided metastatic homing. Although targeting the relatively featureless surface of CXCL12 was presumed to be challenging, focusing efforts at the sulfotyrosine (sY) binding pockets proved successful for procuring initial hits. Using a hybrid structure-based in silico/NMR screening strategy, we recently identified a ligand that occludes the receptor recognition site. From this initial hit, we designed a small fragment library containing only nine tetrazole derivatives using a fragment-based and bioisostere approach to target the sY binding sites of CXCL12. Compound binding modes and affinities were studied by 2D NMR spectroscopy, X-ray crystallography, molecular docking and cell-based functional assays. Our results demonstrate that the sY binding sites are conducive to the development of high affinity inhibitors with better ligand efficiency (LE) than typical protein-protein interaction inhibitors (LE ≤ 0.24). Our novel tetrazole-based fragment 18 was identified to bind the sY21 site with a Kd of 24 μM (LE = 0.30). Optimization of 18 yielded compound 25 which specifically inhibits CXCL12-induced migration with an improvement in potency over the initial hit 9. The fragment from this library that exhibited the highest affinity and ligand efficiency (11: Kd = 13 μM, LE = 0.33) may serve as a starting point for development of inhibitors targeting the sY12 site. PMID:23368099

Photoelectron Spectroscopy of Nitrogen Containing Molecules of Biological and Industrial Interest

NASA Astrophysics Data System (ADS)

Pinto, Rui Montenegro Val-do-Rio

The work presented herein is based on the gas-phase spectroscopic characterization of several molecules of high nitrogen content which are relevant to organic synthesis, industry and fundamental research on molecular physics. It is mainly an experimental enterprise on selected organic azides and tetrazoles, with heavy support on theoretical results from readily available computational methods. Part of the work relies on the design and construction of scientific apparatus, which substantially improve the existing equipment and extend the limits of the experiment. The electronic structure and gas-phase thermal decomposition of methyl 2-azidopropionate (M2AP, N3CH3CHCO2CH 3), benzyl azide (BA, C6H5CH2N 3), 2-, 3- and 4- methyl benzyl azide (2-, 3- and 4-MBA, CH3C 6H4CH2N3), 5-aminotetrazole (5ATZ, NH2CN4H), and 5-methyltetrazole (5MTZ, CH3CN 4H) are investigated through photoelectron spectroscopy, using either He(I) (21.22 eV) or synchrotron radiation in the Xray range. Relevant information obtained from mass spectrometry and matrix-isolation infrared spectroscopy is used to complement characterization of the samples. Regarding each molecules' thermal decomposition, pathways are proposed which account for the observed end products. Conformational analysis is performed, and the special case of annular tautomerism is addressed in the tetrazole compounds. High-temperature pyrolysis work is performed in collaboration with the University of Southampton, and XPS analysis using synchrotron radiation is performed at Elettra, the multidisciplinary synchrotron light laboratory in Trieste, Italy. Experimental findings are rationalized using different computational methods, based on post-Hartree-Fock approaches: many-body perturbation theory (MPn), configuration interaction (CI) and Green's function methods (OVGF, P3), as well as density functional theory (DFT), are used extensively to obtain optimized molecular geometries, ionization energies, orbital contours, relative energies, vibrational frequencies, and to assess possible pathways for thermal or electron impact fragmentation. Composite methods (G n and CBS) are used to estimate to kcal mol-1 accuracy the energy balance between reactants, transition structures and products in the overall decomposition process of the specified molecules.

A novel dumbbell-like polyoxometalate assembled of copper(II)-disubstituted monovacant keggin polyoxoanions with a tetranuclear copper cluster.

PubMed

Miao, Hao; Xu, Xiao; Ju, Wei-Wei; Wan, Hong-Xiang; Zhang, Yu; Zhu, Dun-Ru; Xu, Yan

2014-03-17

A dimeric Keggin polyoxometalate, [Cu(bpy)(μ2-OH)]4[(H2O)(bpy)2HPW11Cu2O39]2·2CH3CH2OH·10H2O (1), constructed from two dicopper(II)-substituted monovacant Keggin polyoxoanions bridged by a Cu4 cluster, has been hydrothermally synthesized. Magnetic analysis indicates predominantly an antiferromagnetic interaction between copper(II) centers. Compound 1 also shows very high catalytic activity for the esterification of phosphoric acid with equimolar lauryl alcohol to monoalkyl phosphate ester.

Synthesis and Characterization of Mono-, Di-, and Tetranitrated 7,8-Disubstituted Glycolurils

DTIC Science & Technology

2014-02-01

Cheetah 7.0 [7] . All of the compounds 8–13 are predicted to have performance values less than TNT with 15 and 16 approaching the performance of TNT...0.25 1.25 0.25 a) Calculated values in brackets. b) Calculated using Cheetah 7.0. c) Peak decomposition temperature at 10 Kmin1 in a pinhole pan. d) Ex...118, 445–458. [7] S. Bastea, L. E. Fried, K. R. Glaesemann, W. M. Howard, I. W. Kuo, P. C. Souers, P. A. Vitello, Cheetah 7.0 User’s Manual, LLNL-SM

Synthesis and antimalarial evaluation of novel isocryptolepine derivatives.

PubMed

Whittell, Louise R; Batty, Kevin T; Wong, Rina P M; Bolitho, Erin M; Fox, Simon A; Davis, Timothy M E; Murray, Paul E

2011-12-15

A series of mono- and di-substituted analogues of isocryptolepine have been synthesized and evaluated for in vitro antimalarial activity against chloroquine sensitive (3D7) and resistant (W2mef) Plasmodium falciparum and for cytotoxicity (3T3 cells). Di-halogenated compounds were the most potent derivatives and 8-bromo-2-chloroisocryptolepine displayed the highest selectivity index (106; the ratio of cytotoxicity (IC(50)=9005 nM) to antimalarial activity (IC(50)=85 nM)). Our evaluation of novel isocryptolepine compounds has demonstrated that di-halogenated derivatives are promising antimalarial lead compounds. Copyright © 2011 Elsevier Ltd. All rights reserved.

Nitromethane with IBX/TBAF as a nitrosating agent: synthesis of nitrosamines from secondary or tertiary amines under mild conditions.

PubMed

Potturi, Hima K; Gurung, Ras K; Hou, Yuqing

2012-01-06

Aliphatic or aromatic N,N-disubstituted nitrosamine was generated in fair to excellent yield from the reaction of a secondary or tertiary amine with o-iodoxybenzoic acid (IBX) or o-iodosylbenzoic acid (IBA)/R(4)NX (X = halide) and nitromethane. The product yield was strongly influenced by both the halide of R(4)NX and iodanes. IBX gave a higher yield than IBA, while the halides follow F(-) > Cl(-) > Br(-) ∼ I(-). Nitrous acid formed in situ from nitromethane and IBX (or IBA)/halides is likely responsible for the observed reaction.

Biting Deterrence and Insecticidal Activity of Hydrazide-Hydrazones and Their Corresponding 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazoles Against Aedes aegypti

DTIC Science & Technology

2012-09-11

against biting insects and later on new insecticides including pyrethroids have been widely used to control a wide range of insect pests in agriculture and...1 to 20 are shown in Table 1. 2.2 Biological activity 2.2.1 Insects The Ae. aegypti (L.) mosquitoes used in these studies were from a laboratory...sucrose solution. Females (5–9 days old) were selected for bioassays. For larval bioassays, the eggs were hatched 1 day prior to testing, and the

One-pot, multicomponent synthesis of 2,3-disubstituted quinazolin-ones with potent and selective activity against Toxoplasma gondii.

PubMed

Brown, Carla E; Kong, Tiffany; Bordón, Claudia; Yolken, Robert; Jones-Brando, Lorraine; McNulty, James

2018-05-15

The discovery of two quinazolinones with selective, single-digit micromolar activity (IC 50  = 6-7 µM) against the tachyzoites of the apicomplexan parasite Toxoplasma gondii is reported. These potent and selective third generation derivatives contain a benzyloxybenzyl substituent at C2 and a bulky aliphatic moiety at N3. Here we show that these quinazolinones inhibit T. gondii tachyzoite replication in an established infection, but do not significantly affect host cell invasion by the tachyzoites. Copyright © 2018 Elsevier Ltd. All rights reserved.

Hybrid dopamine uptake blocker-serotonin releaser ligands: a new twist on transporter-focused therapeutics.

PubMed

Blough, Bruce E; Landavazo, Antonio; Partilla, John S; Baumann, Michael H; Decker, Ann M; Page, Kevin M; Rothman, Richard B

2014-06-12

As part of our program to study neurotransmitter releasers, we report herein a class of hybrid dopamine reuptake inhibitors that display serotonin releasing activity. Hybrid compounds are interesting since they increase the design potential of transporter related compounds and hence represent a novel and unexplored strategy for therapeutic drug discovery. A series of N-alkylpropiophenones was synthesized and assessed for uptake inhibition and release activity using rat brain synaptosomes. Substitution on the aromatic ring yielded compounds that maintained hybrid activity, with the two disubstituted analogues (PAL-787 and PAL-820) having the most potent hybrid activity.

The Application of Vinylogous Iminium Salt Derivatives and Microwave Accelerated Vilsmeier-Haack Reactions to Efficient Relay Syntheses of the Polycitone and Storniamide Natural Products

PubMed Central

Gupton, John T.; Banner, Edith J.; Sartin, Melissa D.; Coppock, Matthew B.; Hempel, Jonathan E.; Kharlamova, Anastasia; Fisher, Daniel C.; Giglio, Ben C.; Smith, Kristin L.; Keough, Matt J.; Smith, Timothy M.; Kanters, Rene P.F.; Dominey, Raymond N.; Sikorski, James A.

2008-01-01

Studies directed at the synthesis of polycitone and storniamide natural products via vinylogous iminium salts and microwave accelerated Vilsmeier-Haack formylations are described. The successful strategy relies on the formation of a 2,4-disubstituted pyrrole or a 2,3,4-trisubstituted pyrrole from a vinamidinium salt or vinamidinium salt derivative followed by formylation at the 5-position of the pyrrole. Subsequent transformations of the selectively formylated pyrroles lead to efficient and regiocontrolled relay syntheses of the respective pyrrole containing natural products. PMID:18709182

Analysis of a thioether lubricant by infrared Fourier microemission spectrophotometry

NASA Technical Reports Server (NTRS)

Jones, W. R., Jr.; Morales, W.; Lauer, J. L.

1986-01-01

An infrared Fourier microemission spectrophotometer is used to obtain spectra (wavenumber range, 630 to 1230 0.1 cm) from microgram quantities of thioether lubricant samples deposited on aluminum foil. Infrared bands in the spectra are reproducible and could be identified as originating from aromatic species (1,3-disubstituted benzenes). Spectra from all samples (neat and formulated, used and unused) are very similar. Additives (an acid and a phosphinate) present in low concentration (0.10 percent) in the formulated fluid are not detected. This instrument appears to be a viable tool in helping to identify lubricant components separated by liquid chromatography.

Study on US/O3 mechanism in p-chlorophenol decomposition

PubMed Central

Xu, Xian-wen; Xu, Xin-hua; Shi, Hui-xiang; Wang, Da-hui

2005-01-01

Study on the effects of sonolysis, ozonolysis and US/O3 system on the decomposition of p-chlorophenol in aqueous solutions indicated that in the cases of US/O3 system, individual ozonolysis and sonolysis, the decomposition rate of p-chlorophenol reached 78.78%, 56.20%, 2.79% after a 16-min reaction while its CODcr (chemical oxygen demand) removal rate was 97.02%, 62.17%, 3.67% after a 120-min reaction. The decomposition reaction of p-chlorophenol follows pseudo-first-order kinetics. The enhancement factors of p-chlorophenol and its CODcr under US/O3 system reached 63% and 237% respectively. The main intermediates during the decomposition include catechol, hydroquinone, p-benzoquinone, phenol, fumaric acid, maleic acid, oxalic acid and formic acid. The decomposition mechanism of p-chlorophenol was also discussed. PMID:15909343

Substance use, childhood sexual abuse, and sexual risk behavior among women in methadone treatment.

PubMed

Cohen, Lisa R; Tross, Susan; Pavlicova, Martina; Hu, Mei-Chen; Campbell, Aimee N; Nunes, Edward V

2009-01-01

Substance use and a history of childhood sexual abuse (CSA) are risk factors for unprotected sex among women, yet questions remain as to how their combined influence may differentially affect sexual risk. The current study investigated how complex relationships among drug use and CSA may contribute to unprotected sexual occasions (USO). A Generalized Linear Mixed Model was used to examine the interaction between current cocaine/stimulants and opioid use and CSA on number of USOs in a sample of 214 sexually active women in outpatient methadone maintenance treatment. For women with CSA, an increase in days of cocaine/stimulant use was associated with a significant increase in USOs. In contrast, an increase in days of opiate use was associated with a significant decrease in USOs. For the group of women who did not report CSA, there was a significant increase in USOs with increased opiate use. Findings indicate that CSA is related to unprotected sexual occasions depending on drug type and severity of use. Women with CSA using cocaine are at particularly high risk for having unprotected sex and should be specifically targeted for HIV prevention interventions.

Dicloruro de paraquat

EPA Pesticide Factsheets

El dicloruro de paraquat, comúnmente conocido como “paraquat,” es uno de los herbicidas registrados de mayor uso en los Estados Unidos. El paraquat también se conoce como Gramaxone (un producto popular de uso final

General Chemistry Division. Quarterly report, July--September 1978

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harrar, J.E.

1978-11-17

Status of the following studies is given: nonaqueous titrimetry; molar absorbance of 1,3,5,-triamine-2,4,6,-trinitrobenzene in dimethylsulfoxide, potentiometric microdetermination of pentaerythritol tetranitrate (PETN) in PETN-containing composites; potentiometric semimicrodetermination of some tetrazoles with silver nitrate; applications of a mode-locked krypton ion laser; time-resolved spectroscopy; photoelectrochemistry; evaluation of a prototype atomic emission source system; laser spectroscopy of neptunium; high-performance liquid chromatography of polyphenyl ether; acquisition of a portable, computerized mass spectrometer; improved inlet for quantitative mass spectrometry; a computer data system for the UTI gas analyzers; analysis of perfluorobutene-2; examination of iridium coatings; source of high-intensity, polarized x rays for fluorescence analysis; mass spectrometermore » for the coal gasification field test; materials protection measurement guides; the LOG system of sample file control; and methylation of platinum compounds by methylcobalamin. (LK)« less

Star-shaped discotic compounds with tetrazole and oxadiazole fragments

NASA Astrophysics Data System (ADS)

Usol'tseva, Nadezhda V.; Akopova, Olga B.; Smirnova, Antonina I.; Kovaleva, Maria I.; Bumbina, Natalia V.; Zharnikova, Nataliia V.

2017-08-01

Two series of star-shaped discotic compounds (A and B) were studied to establish the relationship between their molecular structure and mesogenity. Series A included 19 three-arm compounds with known mesomorphism. Series B consisted of 132 new compounds with unknown mesomorphism: pyromellitic and cyanuric acid derivatives, 5,5‧-azo-bis-isophthalic and 4,4‧-azodiphthalic acids and triphenylene derivatives. The columnar mesomorphism prediction data for both series were obtained using the original program СМР ChemCard. The prediction data for series A are in good agreement with the experimental results and the reliability of the prediction was estimated to be 89.5%. The same method was applied for series B. The prediction results were approved by the synthesis of individual representatives of series B. A good correlation of the prediction with the experimental data was revealed.

Biting deterrence and insecticidal activity of hydrazide-hydrazones and their corresponding 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazoles against Aedes aegypti.

PubMed

Tabanca, Nurhayat; Ali, Abbas; Bernier, Ulrich R; Khan, Ikhlas A; Kocyigit-Kaymakcioglu, Bedia; Oruç-Emre, Emine E; Unsalan, Seda; Rollas, Sevim

2013-06-01

Taking into account the improvement in insecticidal activity by the inclusion of fluorine in the hydrazone moiety, the authors synthesized new 4-fluorobenzoic acid hydrazides and 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazoles, substituting a phenyl group or a heteroaryl ring carrying one or two atoms of F, Cl and Br, and investigated their biting deterrent and larvicidal activities against Aedes aegypti for the first time. The compound 3-acetyl-5-(4-fluorophenyl)-2-[4-(dimethylamino)phenyl]-2,3-dihydro-1,3,4-oxadiazole (17) produced the highest biting deterrent activity (BDI = 1.025) against Ae. Aegypti, followed by 4-fluorobenzoic acid [(phenyl)methylene] hydrazide (1). These activity results were similar to those of N,N-diethyl-meta-toluamide (DEET), which showed a proportion not biting of 0.8-0.92. When compounds 1 and 17 were tested on cloth worn on human volunteers, compound 1 was not repellent for some volunteers until present in excess of 500 nmol cm(-2) , while compound 17 was not repellent at the highest concentration tested (1685 nmol cm(-2) ). In the larvicidal screening bioassays, only compounds 10, 11, 12 and 17 showed 100% mortality at the highest screening dose of 100 ppm against Ae. aegypti larvae. Compounds 11 and 12 with LD50 values of 24.1 and 30.9 ppm showed significantly higher mortality than 10 (80.3 ppm) and 17 (58.7 ppm) at 24-h post-treatment. The insecticidal and biting deterrent activities were correlated with the presence of a halogen atom on the phenyl or heteroaryl substituent of the hydrazone moiety. © 2012 Society of Chemical Industry.

On the molecular and supramolecular properties of N,N‧-disubstituted iminoisoindolines: Synthesis, spectroscopy, X-ray structure and Hirshfeld surface analyses, and DFT calculations of two (E)-N,N‧-bis(aryl)iminoisoindolines (aryl = 2-tert-butylphenyl or perfluorophenyl)

NASA Astrophysics Data System (ADS)

Bitzer, Rodrigo S.; Visentin, Lorenzo C.; Hörner, Manfredo; Nascimento, Marco A. C.; Filgueiras, Carlos A. L.

2017-02-01

Supramolecular studies of iminoisoindoline-derived compounds have been prompted by their biological and photophysical properties. In this article, we report the synthesis, spectroscopy, X-ray structural characterization, and DFT study of two N,N‧-(aryl)-disubstituted 1-iminoisoindolines, namely (E)-N,N‧-bis(2-tert-butylphenyl)iminoisoindoline (2-t-BuPhimiso) and (E)-N,N‧-bis(perfluorophenyl)iminoisoindoline (F5Phimiso). Our X-ray structural analyses have shown that the isoindoline N2 atom of 2-t-BuPhimiso is slightly pyramidalized whereas the respective atom of F5Phimiso displays the expected trigonal planar geometry. The supramolecular arrangement of 2-t-BuPhimiso comprises one-dimensional chains along the [101] direction formed by Csbnd H···πarene interactions, in which the isoindoline ring behaves as a hydrogen-bond donor. For 2-t-BuPhimiso, DFT calculations at the B97-D3/6-311G** level have shown that the dimer formed by this Csbnd H···πarene contact displays a binding energy of -12.83 kcal mol-1. Product F5Phimiso assembles in the crystal state through type-I F3 synthons in addition to Csbnd H⋯F, C-Fδ-···πF+, and πarene/F-πarene/F stacking interactions. Accordingly, our DFT-D3 calculations have confirmed that these interactions synergistically play a dominating role in the crystal packing of F5Phimiso. Finally, the relative stability of the (Z) and (E) isomers of each product has been evaluated at the DFT level of theory. Our calculations have shown that the (E) forms are the most stable ones.

Coordination chemistry and catalytic activity of N-heterocyclic carbene iridium(I) complexes.

PubMed

Fu, Ching-Feng; Chang, Yung-Hung; Liu, Yi-Hong; Peng, Shei-Ming; Elsevier, Cornelis J; Chen, Jwu-Ting; Liu, Shiuh-Tzung

2009-09-21

Iridium complexes [(CO)2Ir(NHC-R)Cl] (R = Et-, 3a; PhCH2-, 3b; CH3OCH2CH2-, 3c; o-CH3OC6H4CH2-, 3d; NHC: N-heterocyclic carbene) are prepared via the carbene transfer from [(NHC-R)W(CO)5] to [Ir(COD)Cl]2. By using substitution with 13CO, we are able to estimate the activation energy (G) of the CO-exchange in 3a-d, which are in the range of 12-13 kcal mol-1, significantly higher than those for the phosphine analog [(CO)2Ir(PCy3)Cl]. Reactions of 3b and 3d with an equimolar amount of PPh3 result in the formation of the corresponding [(NHC-R)Ir(CO)(PPh3)Cl] with the phosphine and NHC in trans arrangement. In contrast, the analogous reaction of 3a or 3c with phosphine undergoes substitution followed by the anion metathesis to yield the corresponding di-substituted [(NHC-R)Ir(CO)(PPh3)2]BF4 (5) directly. Treatment of 3b or 3d with excess of PPh3 leads to the similar product of disubstitution 5b and 5d. The analysis for the IR data of carbonyliridium complexes provides the estimation of electron-donating power of NHCs versus phosphines. The NHC moiety on the iridium center cannot be replaced by phosphines, even 1,2-bis(diphenylphohino)ethane (dppe). All the carbene moieties on the iridium complexes are inert toward sulfur treatment, indicating a strong interaction between NHC and the iridium centers. Complexes 3a-c are active on the catalysis of the oxidative cyclization of 2-(o-aminophenyl)ethanol to yield the indole compound. The phosphine substituted complexes or analogs are less active.

Genetic and structural elucidation of capsular polysaccharides from Streptococcus pneumoniae serotype 23A and 23B, and comparison to serotype 23F.

PubMed

Ravenscroft, Neil; Omar, Aneesa; Hlozek, Jason; Edmonds-Smith, Cesarina; Follador, Rainer; Serventi, Fabio; Lipowsky, Gerd; Kuttel, Michelle M; Cescutti, Paola; Faridmoayer, Amirreza

2017-10-10

Streptococcus pneumoniae is a globally important encapsulated human pathogen with approximately 100 different serotypes recognized. Serogroup 23 consists of serotype 23F, present in licensed vaccines, and emerging serotypes 23A and 23B. Here, we report the previously unknown structures of the pneumococcal capsular polysaccharides serotype 23A and 23B determined using genetic analysis, NMR spectroscopy, composition and linkage analysis and Smith degradation (of polysaccharide 23A). The structure of the serotype 23A capsular polysaccharide is: →4)-β-D-Glcp-(1→3)-[[α-L-Rhap-(1→2)]-[Gro-(2→P→3)]-β-D-Galp-(1→4)]-β-L-Rhap-(1→. This structure differs from polysaccharide 23F as it features a disaccharide backbone and the di-substituted β-Gal is linked to β-Rha as a side chain. This is due to the different polymerization position catalysed by the unusually divergent repeat unit polymerase Wzy in the 23A cps biosynthesis locus. Steric crowding in 23A, confirmed by molecular models, causes the NMR signal for H-1 of the di-substituted 2,3-β-Gal to resonate in the α-anomeric region. The structure of the serotype 23B capsular polysaccharide is the same as 23F, but without the terminal α-Rha: →4)-β-D-Glcp-(1→4)-[Gro-(2→P→3)]-β-D-Galp-(1→4)-β-L-Rhap-(1→. The immunodominant terminal α-Rha of 23F is more sterically crowded in 23A and absent in 23B. This may explain the reported typing cross reactions for serotype 23F: slight with 23A and none with 23B. Copyright © 2017 Elsevier Ltd. All rights reserved.

Symmetrically tetrasubstituted [2.2]paracyclophanes: their systematization and regioselective synthesis of several types of bis-bifunctional derivatives by double electrophilic substitution.

PubMed

Vorontsova, Natalia V; Rozenberg, Valeria I; Sergeeva, Elena V; Vorontsov, Evgenii V; Starikova, Zoya A; Lyssenko, Konstantin A; Hopf, Henning

2008-01-01

The possible number of chiral and achiral tetrasubstituted [2.2]paracyclophanes possessing different types of symmetry (C(2), C(i), C(s), C(2v), C(2h)) is evaluated and a unified independent trivial naming descriptor system is introduced. The reactivity and regioselectivity of the electrophilic substitution of the chiral pseudo-meta- and achiral pseudo-para-disubstituted [2.2]paracyclophanes are investigated in an approach suggested to be general for the synthesis of bis-bifunctional [2.2]paracyclophanes. The mono- and diacylation of chiral pseudo-meta-dihydroxy[2.2]paracyclophane 14 with acetylchloride occur ortho-regioselectively to produce tri- 22, 23 and symmetrically 21 tetrasubstituted acyl derivatives. The same reaction with benzoylchloride is neither regio-, nor chemoselective, and gives rise to a mixture of ortho-/para-, mono-/diacylated compounds 27-31. The double acylation of pseudo-meta-dimethoxy[2.2]paracyclophane 18 is completely para-regioselective. Electrophilic substitution of pseudo-meta-bis(methoxycarbonyl)[2.2]paracyclophane 20 regioselectively generates the pseudo-gem-substitution pattern. Formylation of this substrate produces the monocarbonyl derivatives 35 only, whereas the Fe-catalyzed bromination may be directed towards mono- 36 or disubstitution 37 products chemoselectively by varying the reactions conditions. The diacylation and dibromination reactions of the respective achiral diphenol 12 and bis(methoxycarbonyl) 40 derivatives of the pseudo-para-structure retain regioselectivities which are characteristic for their pseudo-meta-regioisomers. Imino ligands 26, 25, and 39, which were obtained from monoacyl- 22 and diacyldihydroxy[2.2]paracyclophanes 21, 38, are tested as chiral ligands in stereoselective Et(2)Zn addition to benzaldehyde producing 1-phenylpropanol with ee values up to 76 %.

A new phosphine oxide host based on ortho-disubstituted dibenzofuran for efficient electrophosphorescence: towards high triplet state excited levels and excellent thermal, morphological and efficiency stability.

PubMed

Han, Chunmiao; Xie, Guohua; Li, Jing; Zhang, Zhensong; Xu, Hui; Deng, Zhaopeng; Zhao, Yi; Yan, Pengfei; Liu, Shiyong

2011-08-01

An efficient host for blue and green electrophosphorescence, 4,6-bis(diphenylphosphoryl)dibenzofuran (o-DBFDPO), with the structure of a short-axis-substituted dibenzofuran was designed and synthesised. It appears that the greater density of the diphenylphosphine oxide (DPPO) moieties in the short-axis substitution configuration effectively restrains the intermolecular interactions, because only very weak π-π stacking interactions could be observed, with a centroid-to-centroid distance of 3.960 Å. The improved thermal stability of o-DBFDPO was corroborated by its very high glass transition temperature (T(g)) of 191 °C, which is the result of the symmetric disubstitution structure. Photophysical investigation showed o-DBFDPO to be superior to the monosubstituted derivative, with a longer lifetime (1.95 ns) and a higher photoluminescent quantum efficiency (61 %). The lower first singlet state excited level (3.63 eV) of o-DBFDPO demonstrates the stronger polarisation effect attributable to the greater number of DPPO moieties. Simultaneously, an extremely high first triplet state excited level (T(1)) of 3.16 eV is observed, demonstrating the tiny influence of short-axis substitution on T(1). The improved carrier injection ability, which contributed to low driving voltages of blue- and green-emitting phosphorescent organic light-emitting diodes (PHOLEDs), was further confirmed by Gaussian calculation. Furthermore, the better thermal and morphological properties of o-DBFDPO and the matched frontier molecular orbital (FMO) levels in the devices significantly reduced efficiency roll-offs. Efficient blue and green electrophosphorescence based on the o-DBFDPO host was demonstrated. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identification of Disubstituted Sulfonamide Compounds as Specific Inhibitors of Hepatitis B Virus Covalently Closed Circular DNA Formation

PubMed Central

Cai, Dawei; Mills, Courtney; Yu, Wenquan; Yan, Ran; Aldrich, Carol E.; Saputelli, Jeffry R.; Mason, William S.; Xu, Xiaodong; Guo, Ju-Tao; Block, Timothy M.

2012-01-01

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) plays a central role in viral infection and persistence and is the basis for viral rebound after the cessation of therapy, as well as the elusiveness of a cure even after extended treatment. Therefore, there is an urgent need for the development of novel therapeutic agents that directly target cccDNA formation and maintenance. By employing an innovative cell-based cccDNA assay in which secreted HBV e antigen is a cccDNA-dependent surrogate, we screened an in-house small-molecule library consisting of 85,000 drug-like compounds. Two structurally related disubstituted sulfonamides (DSS), termed CCC-0975 and CCC-0346, emerged and were confirmed as inhibitors of cccDNA production, with low micromolar 50% effective concentrations (EC50s) in cell culture. Further mechanistic studies demonstrated that DSS compound treatment neither directly inhibited HBV DNA replication in cell culture nor reduced viral polymerase activity in the in vitro endogenous polymerase assay but synchronously reduced the levels of HBV cccDNA and its putative precursor, deproteinized relaxed circular DNA (DP-rcDNA). However, DSS compounds did not promote the intracellular decay of HBV DP-rcDNA and cccDNA, suggesting that the compounds interfere primarily with rcDNA conversion into cccDNA. In addition, we demonstrated that CCC-0975 was able to reduce cccDNA biosynthesis in duck HBV-infected primary duck hepatocytes. This is the first attempt, to our knowledge, to identify small molecules that target cccDNA formation, and DSS compounds thus potentially serve as proof-of-concept drug candidates for development into therapeutics to eliminate cccDNA from chronic HBV infection. PMID:22644022

Virtual libraries of tetrapyrrole macrocycles. Combinatorics, isomers, product distributions, and data mining.

PubMed

Taniguchi, Masahiko; Du, Hai; Lindsey, Jonathan S

2011-09-26

A software program (PorphyrinViLiGe) has been developed to enumerate the type and relative amounts of substituted tetrapyrrole macrocycles in a virtual library formed by one of four different classes of reactions. The classes include (1) 4-fold reaction of n disubstituted heterocycles (e.g., pyrroles or diiminoisoindolines) to form β-substituted porphyrins, β-substituted tetraazaporphyrins, or α- or β-substituted phthalocyanines; (2) combination of m aminoketones and n diones to form m × n pyrroles, which upon 4-fold reaction give β-substituted porphyrins; (3) derivatization of an 8-point tetrapyrrole scaffold with n reagents, and (4) 4-fold reaction of n aldehydes and pyrrole to form meso-substituted porphyrins. The program accommodates variable ratios of reactants, reversible or irreversible reaction (reaction classes 1 and 2), and degenerate modes of formation. Pólya's theorem (for enumeration of cyclic entities) has also been implemented and provides validation for reaction classes 3 and 4. The output includes the number and identity of distinct reaction-accessible substituent combinations, the number and identity of isomers thereof, and the theoretical mass spectrum. Provisions for data mining enable assessment of the number of products having a chosen pattern of substituents. Examples include derivatization of an octa-substituted phthalocyanine with eight reagents to afford a library of 2,099,728 members (yet only 6435 distinct substituent combinations) and reversible reaction of six distinct disubstituted pyrroles to afford 2649 members (yet only 126 distinct substituent combinations). In general, libraries of substituted tetrapyrrole macrocycles occupy a synthetically accessible region of chemical space that is rich in isomers (>99% or 95% for the two examples, respectively).

1,2,3-Triazole Rings as a Disulfide Bond Mimetic in Chimeric AGRP-Melanocortin Peptides: Design, Synthesis, and Functional Characterization.

PubMed

Tala, Srinivasa R; Singh, Anamika; Lensing, Cody J; Schnell, Sathya M; Freeman, Katie T; Rocca, James R; Haskell-Luevano, Carrie

2018-05-16

The melanocortin system is involved in the regulation of complex physiological functions, including energy and weight homeostasis, feeding behavior, inflammation, sexual function, pigmentation, and exocrine gland function. The five melanocortin receptors that belong to the superfamily of G protein-coupled receptors (GPCRs) are regulated by endogenously expressed agonists and antagonists. The aim of this study was to explore the potential of replacing the disulfide bridge in chimeric AGRP-melanocortin peptide Tyr-c[Cys-His-d-Phe-Arg-Trp-Asn-Ala-Phe-Cys]-Tyr-NH 2 (1) with 1,2,3-triazole moieties. A series of 1,2,3-triazole-bridged peptidomimetics were designed, synthesized, and pharmacologically evaluated at the mouse melanocortin receptors. The ligands possessed nanomolar to micromolar agonist cAMP signaling potency. A key finding was that the disulfide bond in peptide 1 can be replaced with the monotriazole ring with minimal effect on the functional activity at the melanocortin receptors. The 1,5-disubstituted triazole-bridged peptide 6 showed equipotent functional activity at the mMC3R and modest 5-fold decreased agonist potency at the mMC4R compared to those of 1. Interestingly, the 1,4- and 1,5-disubstituted isomers of the triazole ring resulted in different selectivities at the receptor subtypes, indicating subtle structural features that may be exploited in the generation of selective melanocortin ligands. Introducing cyclic and acyclic bis-triazole moieties into chimeric AGRP template 1 generally decreased agonist activity. These results will be useful for the further design of neuronal chemical probes for the melanocortin receptors as well as in other receptor systems.

Comparison of the frequency estimation of the DORIS/Jason2 oscillator thanks to the onboard DIODE and Time Transfer by Laser Link experiment

NASA Astrophysics Data System (ADS)

Jayles, C.; Exertier, P.; Martin, N.; Chauveau, J. P.; Samain, E.; Tourain, C.; Auriol, A.; Guillemot, P.

2016-12-01

The main applications for DORIS are precise orbit determination, and precise Geodesy. Onboard Jason-2 for instance, the DORIS tracking component is the French contribution to the precise orbit determination capability, a key capability for altimetry product scientific result accuracy. T2L2 is a time transfer technique based on the propagation of light pulses for synchronization between two clocks. Hosting T2L2 on-board Jason-2 was to allow for very fine DORIS USO (Ultra-Stable Oscillator) frequency monitoring, and for this purpose T2L2 was connected to the DORIS USO. Thanks to the continuous tracking of T2L2/Jason-2 by the Laser Ranging network it is possible to monitor the USO for several days, weeks, and even much longer, and thus to also compare with the DIODE (the DORIS on-board orbit determination software) frequency bias estimates. The DORIS USO frequency biases estimate comparison between two independent systems, T2L2 and DIODE, can be of benefit to both, allowing the accuracies of both systems to be better understood, and for improvements to be made to both systems. Such comparison is the central topic of the present paper. T2L2 monitors the DORIS on-board USO frequency with an accuracy of much better than 10-12 which is the specification for the Doppler instrumentation. The paper investigates the limits of the DORIS-DIODE frequency bias estimates using T2L2, showing that USO frequency compliance accuracy of 10-12 has been reached.

Defense.gov Special Report: Medal of Honor

Science.gov Websites

Recipients Joint Chiefs of Staff, USO Salute Medal of Honor Recipients At an awards dinner, members of the the USO-Metro's 33rd Annual Awards Dinner in Arlington, Va., March 24, 2015, where they shared their

Sociodemographic profile of medicines users in Brazil: results from the 2014 PNAUM survey.

PubMed

Bertoldi, Andréa Dâmaso; Pizzol, Tatiane da Silva Dal; Ramos, Luiz Roberto; Mengue, Sotero Serrate; Luiza, Vera Lucia; Tavares, Noemia Urruth Leão; Farias, Mareni Rocha; Oliveira, Maria Auxiliadora; Arrais, Paulo Sergio Dourado

2016-12-01

To analyze the prevalence of medicine use by the Brazilian population and its distribution according to sociodemographic factors. Study using data from the Pesquisa Nacional de Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM - National Survey on Access, Use and Promotion of Rational Use of Medicines), a nationwide household survey of a representative sample of the Brazilian urban population. The data were collected between September 2013 and February 2014. The overall use of medicines, defined as the use of any medicine, use of medicines for treating chronic medical conditions and for acute health conditions, was evaluated. The independent variables included gender, age group, socioeconomic position, and region of Brazil. Analyzes included prevalence calculations, 95% confidence intervals (95%CI) and Pearson Chi-square tests to evaluate the differences between groups, considering a 5% level of significance. The prevalence of medicines use was 50.7% (95%CI 49.3-52.2), with 39.3% (95%CI 37.5-41.1) accounting for men and 61.0% (95%CI 59.3-62.6) for women. Medicines use was observed to increase with increasing age, except among children within the zero to four years age group. The lowest prevalence for medicines use was found among those with a low socioeconomic position and those who reside in the North region of Brazil. The prevalence of medicine use to treat chronic diseases was 24.3% (95%CI 23.3-25.4), whereas it was 33.7% (95%CI 32.1-35.4) for treating acute diseases. We found extensive variability in the prevalence of medicines use across regions of Brazil. The poorest regions (North, Northeast, and Midwest) have a lower prevalence of medicines use to treat chronic diseases, indicating the need to minimize inequalities in access to medicines within the country. Analisar a prevalência do uso de medicamentos pela população brasileira e sua distribuição segundo aspectos sociodemográficos. Estudo com dados da Pesquisa Nacional de Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM), pesquisa nacional de base populacional, realizada entre setembro de 2013 e fevereiro de 2014 em residências de municípios urbanos. Avaliou-se o uso de todos os medicamentos (global), uso de medicamentos para doenças crônicas e uso de medicamentos para doenças agudas. As variáveis independentes utilizadas foram sexo, idade, classificação econômica e região do País. Foram calculados prevalências e intervalos de confiança de 95% (IC95%) e aplicado teste Qui-quadrado de Pearson para avaliação das diferenças entre os grupos, considerando o nível de significância de 5%. A prevalência global de uso de medicamentos foi de 50,7% (IC95% 49,3-52,2), sendo 39,3% (IC95% 37,5-41,1) no sexo masculino e 61,0% (IC95% 59,3-62,6) no sexo feminino. Observou-se aumento nas prevalências de uso com a idade (exceto de zero a quatro anos). As menores prevalências de uso ocorreram no grupo mais pobre e na região Norte do País. A prevalência de uso de medicamentos para doenças crônicas foi de 24,3% (IC95% 23,3-25,4) e para doenças agudas foi de 33,7% (IC95% 32,1-35,4). Existe grande variabilidade nas prevalências globais de uso de medicamentos por regiões brasileiras. As regiões consideradas mais pobres (Norte, Nordeste e Centro-Oeste) apresentam menores prevalências de uso de medicamentos para doenças crônicas, o que indica a necessidade de minimizar as desigualdades no acesso aos medicamentos dentro do País.

Defense.gov - Special Report: Travels with Mullen

Science.gov Websites

, 2010 Top Stories Mullen, USO Performers Thank Troops KUWAIT CITY, Kuwait, April 1, 2010 – U.S. Navy Sirico and Rose McGowan, and Brian Stinchcomb of the New Orleans Saints on a USO sponsored tour of

Facile preparation of a new BINAP-based building block, 5,5'-diiodoBINAP, and its synthetic application.

PubMed

Shimada, Toyoshi; Suda, Masahiko; Nagano, Toyohiro; Kakiuchi, Kiyomi

2005-11-25

[reaction: see text] Bis(pyridine)iodonium tetrafluoroborate was successfully used for regioselective iodination of BINAP dioxide to give 5,5'-diiodoBINAP dioxide in an excellent yield of 92%, with no observed formation of 4,4'-diiodoBINAP dioxide. A Sonogashira cross-coupling reaction with 5,5'-diiodoBINAP dioxide gave the desired bis(trimethylsilylethynyl) product in 86% yield. The resulting 5,5'-disubstituted BINAP dioxides were reduced to the corresponding phosphines, which were used as chiral ligands for rhodium-catalyzed asymmetric 1,4-addition of phenylboronic acid to 2-cyclohexenone to give 3-phenylcyclohexanone in excellent yield with high enantioselectivity.

Development of 1-aryl-3-furanyl/thienyl-imidazopyridine templates for inhibitors against hypoxia inducible factor (HIF)-1 transcriptional activity.

PubMed

Fuse, Shinichiro; Ohuchi, Toshiaki; Asawa, Yasunobu; Sato, Shinichi; Nakamura, Hiroyuki

2016-12-15

1,3-Disubstituted-imidazopyridines were designed for developing inhibitors against HIF-1 transcriptional activity. Designed compounds were rapidly synthesized from a key aromatic scaffold via microwave-assisted Suzuki-Miyaura coupling/CH direct arylation sequence. Evaluation of ability to inhibit the hypoxia induced transcriptional activity of HIF-1 revealed that the compound 2i and 3a retained the same level of the inhibitory activity comparing with that of known inhibitor, YC-1 (1). Identified, readily accessible 1-aryl-3-furanyl/thienyl-imidazopyridine templates should be useful for future drug development. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthesis and antitumour activity of 4-aminoquinazoline derivatives

NASA Astrophysics Data System (ADS)

Lipunova, G. N.; Nosova, E. V.; Charushin, V. N.; Chupakhin, O. N.

2016-07-01

Pieces of data on the synthesis and antitumour activity of 4-aminoquinazolines are summarized and analyzed. Key methods for the synthesis of these compounds are considered, primarily cyclocondensation of carboxylic acid derivatives, as well as the oxidation of quinazolines and the cyclization of disubstituted thioureas. Improvements of synthetic schemes for erlotinib, gefitinib and lapatinib, which are the best-known pharmaceuticals based on compounds of the title class, are also considered. Synthetic strategies and biological activities for new 4-aminoquinazoline derivatives that are EGFR-tyrosine kinase inhibitors, multiactive compounds, and labelled compounds for use as positron emission tomography (PET) imaging agents are discussed. The bibliography includes 263 references.

BCl3‐Induced Annulative Oxo‐ and Thioboration for the Formation of C3‐Borylated Benzofurans and Benzothiophenes

PubMed Central

Warner, Andrew J.; Churn, Anna; McGough, John S.

2016-01-01

Abstract BCl3‐induced borylative cyclization of aryl‐alkynes possessing ortho‐EMe (E=S, O) groups represents a simple, metal‐free method for the formation of C3‐borylated benzothiophenes and benzofurans. The dichloro(heteroaryl)borane primary products can be protected to form synthetically ubiquitous pinacol boronate esters or used in situ in Suzuki–Miyaura cross couplings to generate 2,3‐disubstituted heteroarenes from simple alkyne precursors in one pot. In a number of cases alkyne trans‐haloboration occurs alongside, or instead of, borylative cyclization and the factors controlling the reaction outcome are determined. PMID:27897368

Discovery of Novel 3,3-Disubstituted Piperidines as Orally Bioavailable, Potent, and Efficacious HDM2-p53 Inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bogen, Stéphane L.; Pan, Weidong; Gibeau, Craig R.

2016-03-10

A new subseries of substituted piperidines as p53-HDM2 inhibitors exemplified by 21 has been developed from the initial lead 1. Research focused on optimization of a crucial HDM2 Trp23–ligand interaction led to the identification of 2-(trifluoromethyl)thiophene as the preferred moiety. Further investigation of the Leu26 pocket resulted in potent, novel substituted piperidine inhibitors of the HDM2-p53 interaction that demonstrated tumor regression in several human cancer xenograft models in mice. The structure of HDM2 in complex with inhibitors 3, 10, and 21 is described.

Asymmetric intramolecular Pauson-Khand reaction mediated by a remote sulfenyl or sulfinyl group.

PubMed

García Ruano, José Luis; Torrente, Esther; Parra, Alejandro; Alemán, José; Martín-Castro, Ana M

2012-08-03

In this work, we report the use of the asymmetric intramolecular Pauson-Khand reactions of 4-aryl-4-cyano-1,6-enynes for obtaining enantiomerically enriched bicyclo[3.3.0]octenones, and the influence of both the quaternary stereocenter and the sulfur functions located at ortho-position of the aryl group, on their stereoselectivity and reactivity. The sulfenyl derivatives bearing substituted or unsubstituted triple bonds and mono- and disubstituted alkene moieties afford bicyclo[3.3.0]octenones in high yields with complete diastereocontrol. These results are explained by assuming the association of the lone electron pair at sulfur to the Co-alkyne complexes.

Structure-based design of a novel series of azetidine inhibitors of the hepatitis C virus NS3/4A serine protease.

PubMed

Parsy, Christophe; Alexandre, François-René; Brandt, Guillaume; Caillet, Catherine; Cappelle, Sylvie; Chaves, Dominique; Convard, Thierry; Derock, Michel; Gloux, Damien; Griffon, Yann; Lallos, Lisa; Leroy, Frédéric; Liuzzi, Michel; Loi, Anna-Giulia; Moulat, Laure; Musiu, Chiara; Rahali, Houcine; Roques, Virginie; Seifer, Maria; Standring, David; Surleraux, Dominique

2014-09-15

Structural homology between thrombin inhibitors and the early tetrapeptide HCV protease inhibitor led to the bioisosteric replacement of the P2 proline by a 2,4-disubstituted azetidine within the macrocyclic β-strand mimic. Molecular modeling guided the design of the series. This approach was validated by the excellent activity and selectivity in biochemical and cell based assays of this novel series and confirmed by the co-crystal structure of the inhibitor with the NS3/4A protein (PDB code: 4TYD). Copyright © 2014 Elsevier Ltd. All rights reserved.

Substance Use, Depression and Sociodemographic Determinants of HIV Sexual Risk Behavior in Outpatient Substance Abuse Treatment Patients.

PubMed

Tross, Susan; Feaster, Daniel J; Thorens, Gabriel; Duan, Rui; Gomez, Zoilyn; Pavlicova, Martina; Hu, Mei Chen; Kyle, Tiffany; Erickson, Sarah; Spector, Anya; Haynes, Louise; Metsch, Lisa R

2015-01-01

The NIDA Clinical Trials Network trial of rapid HIV testing/counseling in 1281 patients was a unique opportunity to examine relationships among substance use, depressive symptoms, and sex risk behavior. Past 6-month substance use; substance use severity (Drug Abuse Screening Test - 10); depressive symptoms (Quick Inventory of Depressive Symptomatology); and three types of sex risk behavior (unprotected sex occasions [USOs] with primary partners; USOs with nonprimary partners; and USOs while high/drunk) were assessed. Zero-inflated negative binomial analyses provided: probability and rate of sex risk behavior (in risk behavior subsample). Levels of sexual risk behavior were high, while variable across the three types of sex risk behaviors. Among the patients, 50.4% had engaged in USOs with primary partners, 42% in sex while drunk or high, and 23.8% in USOs with nonprimary partners. Similar factors were significantly associated with all three types of sex risk behaviors. For all types, problem drinking, cocaine use, and substance use severity had an exacerbating effect. Older age was associated with lower risk behavior; other relationship categories (eg, married, separated/divorced, cohabitating) were associated with greater risk behavior than was single status. Depressive symptoms were associated with decreased likelihood of USOs with a primary partner. Sexual risk behavior is common among individuals in outpatient substance abuse treatment. Results highlight problem drinking (eg, up to three-fold) and cocaine (eg, up to twice) in increasing sex risk behavior. They demonstrate the utility of distinguishing between partner types and presence/absence of alcohol/drugs during sex. Findings argue for the need to integrate sex risk reduction into drug treatment.

Perfil das alterações vasculares periféricas em dependentes de crack acompanhados em Centro de Atenção Psicossocial para Álcool e Drogas (CAPS-AD)

PubMed Central

da Costa, Antônio Fagundes; Baldaçara, Leonardo Rodrigo; da Silva, Sílvio Alves; Tavares, Ana Célia de Freitas Ramos; Orsolin, Ederson de Freitas; Prehl, Vinícius Barros; Gondo, Fernando Hirohito Beltran; Santana, Hernani Lopes

2016-01-01

Resumo Contexto O consumo de crack é um dos grandes desafios em saúde pública, e o uso dessa droga tem efeitos diretos na saúde de seus usuários. Objetivos Avaliar o perfil das alterações vasculares em pacientes com dependência de crack em Centro de Atenção Psicossocial para Álcool e Drogas (CAPS-AD) e observar os possíveis efeitos vasculares periféricos. Métodos Trata-se de um estudo observacional, descritivo, de corte transversal. Os pacientes da amostra foram submetidos a um questionário objetivo para avaliar questões demográficas, padrão de uso da droga, coexistência de diabetes melito, hipertensão arterial ou tabagismo, exame físico e ecográfico. Os dados foram sumarizados e analisados estatisticamente com teste qui-quadrado ou teste exato de Fisher. Resultados A média de idade da amostra foi de 33,29 (±7,15) anos, e 74% eram do gênero masculino. A média de idade de início de uso da droga foi de 23,4 (±7,78) anos, com tempo médio de uso de 9,58 (±5,64) anos. O consumo médio diário de pedras de crack foi de 21,45 (±8,32) pedras. A alteração de pulsos em membros inferiores foi mais frequente em mulheres. A prevalência do espessamento da parede arterial nos membros inferiores foi de 94,8%. O tempo de uso da droga apresentou associação estatística (p = 0,0096) com alteração do padrão de curva espectral das artérias dos membros inferiores. Conclusões Há alterações vasculares periféricas em usuários de crack. O tempo de uso da droga exerceu um maior impacto nesse sistema, o que sugere associação entre o uso do crack e a diminuição de fluxo arterial.

Porous MOF with Highly Efficient Selectivity and Chemical Conversion for CO2.

PubMed

Wang, Hai-Hua; Hou, Lei; Li, Yong-Zhi; Jiang, Chen-Yu; Wang, Yao-Yu; Zhu, Zhonghua

2017-05-31

A new Co(II)-based MOF, {[Co 2 (tzpa)(OH)(H 2 O) 2 ]·DMF} n (1) (H 3 tzpa = 5-(4-(tetrazol-5-yl)phenyl)isophthalic acid), was constructed by employing a tetrazolyl-carboxyl ligand H 3 tzpa. 1 possesses 1D tubular channels that are decorated by μ 3 -OH groups, uncoordinated carboxylate O atoms, and open metal centers generated by the removal of coordinated water molecules, leading to high CO 2 adsorption capacity and significantly selective capture for CO 2 over CH 4 and CO in the temperature range of 298-333 K. Moreover, 1 shows the chemical stability in acidic and basic aqueous solutions. Grand canonical Monte Carlo simulations identified multiple CO 2 -philic sites in 1. In addition, the activated 1 as the heterogeneous Lewis and Brønsted acid bifunctional catalyst facilitates the chemical fixation of CO 2 coupling with epoxides into cyclic carbonates under ambient conditions.

Synthesis and methemoglobinemia-inducing properties of benzocaine isosteres designed as humane rodenticides.

PubMed

Conole, Daniel; Beck, Thorsten M; Jay-Smith, Morgan; Tingle, Malcolm D; Eason, Charles T; Brimble, Margaret A; Rennison, David

2014-04-01

A number of isosteres (oxadiazoles, thiadiazoles, tetrazoles and diazines) of benzocaine were prepared and evaluated for their capacity to induce methemoglobinemia-with a view to their possible application as humane pest control agents. It was found that an optimal lipophilicity for the formation of methemoglobin (metHb) in vitro existed within each series, with 1,2,4-oxadiazole 3 (metHb%=61.0±3.6) and 1,3,4-oxadiazole 10 (metHb%=52.4±0.9) demonstrating the greatest activity. Of the 5 candidates (compounds 3, 10, 11, 13 and 23) evaluated in vivo, failure to induce a lethal end-point at doses of 120mg/kg was observed in all cases. Inadequate metabolic stability, particularly towards hepatic enzymes such as the CYPs, was postulated as one reason for their failure. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fluorogenic Ag+–Tetrazolate Aggregation Enables Efficient Fluorescent Biological Silver Staining

PubMed Central

Xie, Sheng; Wong, Alex Y. H.; Kwok, Ryan T. K.; Li, Ying; Su, Huifang; Lam, Jacky W. Y.

2018-01-01

Abstract Silver staining, which exploits the special bioaffinity and the chromogenic reduction of silver ions, is an indispensable visualization method in biology. It is a most popular method for in‐gel protein detection. However, it is limited by run‐to‐run variability, background staining, inability for protein quantification, and limited compatibility with mass spectroscopic (MS) analysis; limitations that are largely attributed to the tricky chromogenic visualization. Herein, we reported a novel water‐soluble fluorogenic Ag+ probe, the sensing mechanism of which is based on an aggregation‐induced emission (AIE) process driven by tetrazolate‐Ag+ interactions. The fluorogenic sensing can substitute the chromogenic reaction, leading to a new fluorescence silver staining method. This new staining method offers sensitive detection of total proteins in polyacrylamide gels with a broad linear dynamic range and robust operations that rival the silver nitrate stain and the best fluorescent stains. PMID:29575702

Synthesis and properties of dithymidine phosphate analogues containing 3'-thiothymidine.

PubMed Central

Cosstick, R; Vyle, J S

1990-01-01

Dithymidine-3'-S-phosphorothioate (d(TspT)) has been prepared from a 5'-O-monomethoxytritylthymidine-3'-S-phosphorothioamidite (7) by activation with 5-(p-nitrophenyl)tetrazole in the presence of 3'-O-acetylthymidine. The resulting dinucleoside phosphorothioite is readily oxidised to the corresponding 3'-S-phosphorothioate using either tetrabutylammonium (TBA) periodate or TBA oxone and has been deprotected under standard conditions to yield d(TspT). This dithymidine phosphate analogue is comparatively resistant to hydrolysis by nuclease P1, but the P-S bond is readily cleaved by aqueous solutions of either iodine or silver nitrate. Dithymidine-3'-S-phosphorodithioate (d[Tsp(s)T]) was prepared in an analogous fashion using sulphur to oxidise the intermediate dinucleoside phosphorothioite. Absolute stereochemistry has been assigned to the diastereoisomers of d[Tsp(s)T] by comparing their physical and chemical properties to those of the dinucleoside phosphorothioates. PMID:2315041

Near Field Enhanced Photocurrent Generation in P-type Dye-Sensitized Solar Cells

PubMed Central

Xu, Xiaobao; Cui, Jin; Han, Junbo; Zhang, Junpei; Zhang, Yibo; Luan, Lin; Alemu, Getachew; Wang, Zhong; Shen, Yan; Xiong, Dehua; Chen, Wei; Wei, Zhanhua; Yang, Shihe; Hu, Bin; Cheng, Yibing; Wang, Mingkui

2014-01-01

Over the past few decades, the field of p-type dye-sensitized solar cell (p-DSSC) devices has undergone tremendous advances, in which Cu-based delafossite nanocrystal is of prime interest. This paper presents an augment of about 87% improvement in photocurrent observed in a particular configuration of organic dye P1 sensitized CuCrO2 delafossite nanocrystal electrode coupled with organic redox shuttle, 1-methy-1H- tetrazole-5-thiolate and its disulfide dimer when Au nanoparticles (NPs, with diameter of about 20 nm) is added into the photocathode, achieving a power convert efficiency of 0.31% (measured under standard AM 1.5 G test conditions). Detailed investigation shows that the local electrical-magnetic field effect, induced by Au NPs among the mesoporous CuCrO2 film, can improve the charge injection efficiency at dye/semiconductor interface, which is responsible for the bulk of the gain in photocurrent. PMID:24492539

New hydrolytically stable solvent for Am/Eu separation in acidic media

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smirnov, I.V.; Babain, V.A.; Chirkov, A.V.

Americium and europium extraction by synergistic mixture of 2,6-bis(1-aryl-1H-tetrazol-5-yl)pyridines (ATP) - chlorinated cobalt dicarbollide (CCD) in polar diluent s from HNO{sub 3} media was studied. Meta-nitro-benzo-trifluoride, phenyl-tri-fluoro-methyl sulfone and 1,2-dichloroethane were used as diluents. The effect of diluent, composition of aqueous phase and substituent nature in aryl ring of ATPs on the extraction efficiency and selectivity of americium and europium separation was investigated. At the optimal ratio of nATP:CCD 1:1 the Am - Eu separation factor exceeded 90. Extraction of {sup 85}Sr, {sup 137}Cs and {sup 133}Ba was investigated and it was found that the mixture nATP-CCD provided the separationmore » of Sr /Ba pair with a factor of 35. High resistance of 2,6-bisaryltetrazolyl pyridines to the action of nitric acid was demonstrated. (authors)« less

Synthesis and characterization of an anomeric sulfur analogue of CMP-sialic acid.

PubMed

Cohen, S B; Halcomb, R L

2000-09-22

alpha-2,3-Sialyltransferase catalyzes the transfer of sialic acid from CMP-sialic acid (1) to a lactose acceptor. An analogue of 1 was synthesized in which the anomeric oxygen atom was replaced with a sulfur atom (1S). The key step in the synthesis of 1S was a tetrazole-promoted coupling of a cytidine-5'-phosphoramidite with a glycosyl thiol of a protected sialic acid. Compounds 1 and 1S were characterized for their activity in a sialyl transfer assay. The rate of solvolysis in aqueous buffer of analogue 1S was 50-fold slower than that of 1. Analogue 1S was found to be substrate for alpha-2,3-sialyltransferase. The K(m) of 1S was just 3-fold higher than that of 1, while the k(cat) of 1S was 2 orders of magnitude lower compared to 1.

76 FR 20392 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-12

..., SMH, SNDK, SPLS, SPXU, SPY, SSO, SYMC, TBT, T, TLT, TNA,TSM, TWM, TXN, TZA, UCO, USO, UWM, UYG, VALE..., S, SH, SLV, SPF, SPXU, SPY, SSO, TBT, TLT, TWM, TZA, UCO, USO, UWM, VXX, XLI, XLP. Transactions in...

Structure and properties of bis(1-phenyl-1h-tetrazole-5-thiolate)diiron tetranitrosyl

NASA Astrophysics Data System (ADS)

Sanina, N. A.; Kozub, G. I.; Kondrat'eva, T. A.; Shilov, G. V.; Korchagin, D. V.; Emel'yanova, N. S.; Poleshchuk, O. Kh.; Chernyak, A. V.; Kulikov, A. V.; Mushenok, F. B.; Ovanesyan, N. S.; Aldoshin, S. M.

2013-06-01

New tetranitrosyl binuclear iron complex [Fe2(SС7H5N4)2(NO)4] (I) has been synthesized by interaction of aqueous solutions of anionic salts [Fе(S2O3)2(NO)2]3- and [SС7H5N4]-. The latter one was synthesized by reduction of bis-(1-phenyl-1H-tetrazole-5-yl) disulfide with hydrazine hydrate in ethanol at T = 25 °C. Molecular and crystalline structure of I was determined by X-ray analysis; the complex has binuclear structure of "μ-SCN" type with ˜4.02 Å between the iron atoms. Shortened О⋯О contacts (2.81 Å) between the NO groups of similar type are observed. Parameters of Mössbauer spectrum for I are: isomer shift δFe = 0.311(1) mm/s, quadrupole splitting ΔEQ = 1.044(1) mm/s, line width Γ = 0.267(1) mm/s at 85 K. From SQUID magnetometry data, the temperature and field dependences of the magnetic moment of I are well described in the frame of a simple model of binuclear iron complex with magnetic centers S1 = S2 = ½. In solution, binuclear structure of the complex remains, though the NO groups are non-equivalent. For solutions of I five-line hyperfine structure of spectrum (HFS) is observed, g-factor = 2.03. For polycrystals of I, no HFS was observed due to averaged exchange interaction between the electron spins of adjacent complexes. In polycrystals of I, the number of spins per one binuclear complex is <2, this being the evidence of antiferromagnetic exchange interaction of unpaired electrons of two iron atoms. The average number of spins in crystals (0.65) and solutions (0.55) are close. The maximum amount of NO generated by I in 1% dimethylsulfoxide (DMSO) aqueous solution is ˜13.8 nM, it halves in 8 min after decomposition starts, and reaches ˜3.8 nM in anaerobic conditions at Т = 25 °С, pH 7.0. This is due, according to quantum-chemical calculations, to the presence of a more stable Fesbnd NO bond in I than in its isostructural analog - nitrosyl iron complex with 1-methyltetrazole-5-yl (II).

Gas-phase behaviour of Ru(II) cyclopentadienyl-derived complexes with N-coordinated ligands by electrospray ionization mass spectrometry: fragmentation pathways and energetics.

PubMed

Madeira, Paulo J Amorim; Morais, Tânia S; Silva, Tiago J L; Florindo, Pedro; Garcia, M Helena

2012-08-15

The gas-phase behaviour of six Ru(II) cyclopentadienyl-derived complexes with N-coordinated ligands, compounds with antitumor activities against several cancer lines, was studied. This was performed with the intent of establishing fragmentation pathways and to determine the Ru-L(N) and Ru-L(P) ligand bond dissociation energies. Such knowledge can be an important tool for the postulation of the mechanisms of action of these anticancer drugs. Two types of instruments equipped with electrospray ionisation were used (ion trap and a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer). The dissociation energies were determined using energy-variable collision-induced dissociation measurements in the ion trap. The FTICR instrument was used to perform MS(n) experiments on one of the compounds and to obtain accurate mass measurements. Theoretical calculations were performed at the density functional theory (DFT) level using two different functionals (B3LYP and M06L) to estimate the dissociation energies of the complexes under study. The influence of the L(N) on the bond dissociation energy (D) of RuCp compounds with different nitrogen ligands was studied. The lability order of L(N) was: imidazole<1-butylimidazole<5-phenyl-1H-tetrazole<1-benzylimidazole. Both the functionals used gave the following ligand lability order: imidazole<1-benzylimidazole<5-phenyl-1H-tetrazole<1-butylimidazole. It is clear that there is an inversion between 1-benzylimidazole and 1-butylimidazole for the experimental and theoretical lability orders. The M06L functional afforded values of D closer to the experimental values. The type of phosphane (L(P) ) influenced the dissociation energies, with values of D being higher for Ru-L(N) with 1-butylimidazole when the phosphane was 1,2-bis(diphenylphosphino)ethane. The Ru-L(P) bond dissociation energy for triphenylphosphane was independent of the type of complex. The D values of Ru-L(N) and Ru-L(P) were determined for all six compounds and compared with the values calculated by the DFT method. For the imidazole-derived ligands the energy trend was rationalized in terms of the increasing extension of the σ-donation/π-backdonation effect. The bond dissociation energy of Ru-PPh(3) was independent of the fragmentations. Copyright © 2012 John Wiley & Sons, Ltd.

A Study of Distance Learning Technology in Utah: A Statewide Overview.

ERIC Educational Resources Information Center

Chow, Stanley H. L.; And Others

This report was commissioned by the Utah State Office of Education (USOE) to provide USOE with information about the potential applications of distance learning technology in schools. The study includes: (1) a statewide assessment of instructional, staff development, and administrative needs which may be met by distance learning technology; and…

Activation of olefins via asymmetric Bronsted acid catalysis

DOE PAGES

Tsuji, Nobuya; Kennemur, Jennifer L.; Buyck, Thomas; ...

2018-03-30

The activation of olefins for asymmetric chemical synthesis traditionally relies on transition metal catalysts. In contrast, biological enzymes with Bronsted acidic sites of appropriate strength can protonate olefins and thereby generate carbocations that ultimately react to form natural products. Although chemists have recently designed chiral Bronsted acid catalysts to activate imines and carbonyl compounds, mimicking these enzymes to protonate simple olefins that then engage in asymmetric catalytic reactions has remained a substantial synthetic challenge. Here, we show that a class of confined and strong chiral Bronsted acids enables the catalytic asymmetric intramolecular hydroalkoxylation of unbiased olefins. In conclusion, the methodologymore » gives rapid access to biologically active 1,1-disubstituted tetrahydrofurans, including (–)-Boivinianin A.« less

Asymmetric nucleophilic monofluorobenzylation of carbonyl compounds: synthesis of enantiopure vic-fluorohydrins and α-fluorobenzylketones.

PubMed

Arroyo, Yolanda; Sanz-Tejedor, M Ascensión; Parra, Alejandro; García Ruano, José Luis

2012-04-23

Asymmetric nucleophilic monofluoroalkylation of a broad range of aldehydes with an α-fluoro-γ-sulfinylbenzyl carbanion takes place with complete control of the facial selectivity at the carbanion and good to high anti-diastereoselectivity to give easily separable mixtures of two optically pure 1,2-fluorohydrin derivatives (up to 24:1 anti/syn). Separation and removal of the p-tolylsulfinyl group with tBuLi provides enantiomerically pure anti-1,2-disubstituted-1,2-fluorohydrins, whereas α-fluorobenzylketones can be obtained by desulfinylation of the mixture followed by pyridinium chlorochromate oxidation (one-pot process). Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of novel di- and tricationic carbapenems with potent anti-MRSA activity.

PubMed

Maruyama, Takahisa; Yamamoto, Yasuo; Kano, Yuko; Kurazono, Mizuyo; Shitara, Eiki; Iwamatsu, Katsuyoshi; Atsumi, Kunio

2009-01-15

A new series of 1beta-methyl carbapenems possessing a 6,7-disubstituted imidazo[5,1-b]thiazol-2-yl group directly attached to the C-2 position of the carbapenem nucleus was prepared, and their activities against methicillin-resistant Staphylococcus aureus (MRSA) were evaluated. First, a benzyl moiety was introduced at the C-6 position of imidazo[5,1-b]thiazole attached to the carbapenem. These benzylated molecules showed potent anti-MRSA activity, but poor water solubility. In order to overcome this drawback, we designed and synthesized di- and tricationic carbapenems and finally discovered a novel carbapenem (15i), which exhibited excellent anti-MRSA activity and good water solubility.

Palladium-catalyzed cyclocoupling of 2-halobiaryls with isocyanides via the cleavage of carbon-hydrogen bonds.

PubMed

Tobisu, Mamoru; Imoto, Shinya; Ito, Sana; Chatani, Naoto

2010-07-16

To demonstrate the utility of isocyanides in catalytic C-H bond functionalization reactions, a palladium-catalyzed cyclocoupling reaction of 2-halobiaryls with isocyanides was developed. The reaction afforded an array of fluorenone imine derivatives via the cleavage of a C-H bond at the 2'-position of 2-halobiaryls. The use of 2,6-disubstituted phenyl isocyanide was crucial for this catalytic cyclocoupling reaction to proceed. The reaction was applicable to heterocyclic and vinylic substrates, allowing the construction of a wide range of ring system. The large kinetic isotope effect observed (k(H)/k(D) = 5.3) indicates that C-H bond activation was the turnover-limiting step in this catalysis.

Activation of olefins via asymmetric Bronsted acid catalysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsuji, Nobuya; Kennemur, Jennifer L.; Buyck, Thomas

The activation of olefins for asymmetric chemical synthesis traditionally relies on transition metal catalysts. In contrast, biological enzymes with Bronsted acidic sites of appropriate strength can protonate olefins and thereby generate carbocations that ultimately react to form natural products. Although chemists have recently designed chiral Bronsted acid catalysts to activate imines and carbonyl compounds, mimicking these enzymes to protonate simple olefins that then engage in asymmetric catalytic reactions has remained a substantial synthetic challenge. Here, we show that a class of confined and strong chiral Bronsted acids enables the catalytic asymmetric intramolecular hydroalkoxylation of unbiased olefins. In conclusion, the methodologymore » gives rapid access to biologically active 1,1-disubstituted tetrahydrofurans, including (–)-Boivinianin A.« less

Consecutive three-component synthesis of (hetero)arylated propargyl amides by chemoenzymatic aminolysis-Sonogashira coupling sequence.

PubMed

Hassan, Sidra; Ullrich, Anja; Müller, Thomas J J

2015-02-07

A novel chemoenzymatic three-component synthesis of (hetero)arylated propargyl amides in good yields based upon Novozyme® 435 (Candida antarctica lipase B (CAL-B)) catalyzed aminolysis of methyl carboxylates followed by Sonogashira coupling with (hetero)aryliodides in a consecutive one-pot fashion has been presented. This efficient methodology can be readily concatenated with a CuAAC (Cu catalyzed alkyne azide cycloaddition) as a third consecutive step to furnish 1,4-disubstituted 1,2,3-triazole ligated arylated propargyl amides. This one-pot process can be regarded as a transition metal catalyzed sequence that takes advantage of the copper source still present from the cross-coupling step.

BCl3 -Induced Annulative Oxo- and Thioboration for the Formation of C3-Borylated Benzofurans and Benzothiophenes.

PubMed

Warner, Andrew J; Churn, Anna; McGough, John S; Ingleson, Michael J

2017-01-02

BCl 3 -induced borylative cyclization of aryl-alkynes possessing ortho-EMe (E=S, O) groups represents a simple, metal-free method for the formation of C3-borylated benzothiophenes and benzofurans. The dichloro(heteroaryl)borane primary products can be protected to form synthetically ubiquitous pinacol boronate esters or used in situ in Suzuki-Miyaura cross couplings to generate 2,3-disubstituted heteroarenes from simple alkyne precursors in one pot. In a number of cases alkyne trans-haloboration occurs alongside, or instead of, borylative cyclization and the factors controlling the reaction outcome are determined. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Catalytic Enantioselective and Diastereoselective Allylic Alkylation with Fluoroenolates: Efficient Access to C3-Fluorinated and All-Carbon Quaternary Oxindoles

PubMed Central

Balaraman, Kaluvu; Wolf, Christian

2017-01-01

Synthetically versatile 3,3-disubstituted fluorooxindoles exhibiting vicinal chirality centers were obtained in high yields and with excellent enantio-, diastereo- and regioselectivity by catalytic asymmetric fluoroenolate alkylation with allylic acetates. The reaction proceeds under mild conditions and can be upscaled without compromising the asymmetric induction. The unique synthetic usefulness of the products is highlighted with the incorporation of additional functionalities and the formation of 3-fluorinated oxindoles exhibiting an array of four adjacent chirality centers. A new C-F bond functionalization path that provides unprecedented means for stereoselective generation of a chiral quaternary carbon center in the alkaloid scaffold is introduced. PMID:28026079

Controlling site selectivity in Pd-catalyzed oxidative cross-coupling reactions.

PubMed

Lyons, Thomas W; Hull, Kami L; Sanford, Melanie S

2011-03-30

This paper presents a detailed investigation of the factors controlling site selectivity in the Pd-mediated oxidative coupling of 1,3-disubstituted and 1,2,3-trisubstituted arenes (aryl-H) with cyclometalating substrates (L~C-H). The influence of both the concentration and the steric/electronic properties of the quinone promoter are studied in detail. In addition, the effect of steric/electronic modulation of the carboxylate ligand is discussed. Finally, we demonstrate that substitution of the carboxylate for a carbonate X-type ligand leads to a complete reversal in site selectivity for many arene substrates. The origins of these trends in site selectivity are discussed in the context of the mechanism of Pd-catalyzed oxidative cross-coupling.

Enantioselective Synthesis of 5,7-Bicyclic Ring Systems from Axially Chiral Allenes Using a Rh(I)-Catalyzed Cyclocarbonylation Reaction

PubMed Central

Grillet, Francois; Brummond, Kay M.

2013-01-01

A transfer of chirality in an intramolecular Rh(I)-catalyzed allenic Pauson-Khand reaction (APKR) to access tetrahydroazulenones, tetrahydrocyclopenta[c]azepinones and dihydrocyclopenta[c]oxepinones enantioselectively (22 – 99% ee) is described. The substitution pattern of the allene affected the transfer of chiral information. Complete transfer of chirality was obtained for all trisubstituted allenes, but loss of chiral information was observed for disubstituted allenes. This work constitutes the first demonstration of a transfer of chiral information from an allene to the 5-position of a cyclopentenone using a cyclocarbonylation reaction. The absolute configuration of the corresponding cyclocarbonylation product was also established, something that is rarely done. PMID:23485149

Progress towards synthetic chlorins with graded polarity, conjugatable substituents, and wavelength tunability

DOE PAGES

Ra, Doyoung; Gauger, Kelly A.; Muthukumaran, Kannan; ...

2015-04-01

Advances in chlorin synthetic chemistry now enable the de novo preparation of diverse chlorin-containing molecular architectures. Five distinct molecular designs have been explored here, including hydrophobic bioconjugatable (oxo)chlorins; a hydrophilic bioconjugatable chlorin; a trans-ethynyl/iodochlorin building block; a set of chlorins bearing electron-rich (methoxy, dimethylamino, methylthio) groups at the 3-position; and a set of ten 3,13-disubstituted chlorins chiefly bearing groups with extended π-moieties. Altogether 23 new chlorins (17 targets, 6 intermediates) have been prepared. Lastly, the challenge associated with molecular designs that encompass the combination of “hydrophilic, bioconjugatable and wavelength-tunable” chiefly resides in the nature of the hydrophilic unit.

Visible-Light Photocatalytic Decarboxylation of α,β-Unsaturated Carboxylic Acids: Facile Access to Stereoselective Difluoromethylated Styrenes in Batch and Flow

PubMed Central

2017-01-01

The development of synthetic methodologies which provide access to both stereoisomers of α,β-disubstituted olefins is a challenging undertaking. Herein, we describe the development of an operationally simple and stereoselective synthesis of difluoromethylated styrenes via a visible-light photocatalytic decarboxylation strategy using fac-Ir(ppy)3 as the photocatalyst. Meta- and para-substituted cinnamic acids provide the expected E-isomer. In contrast, ortho-substituted cinnamic acids yield selectively the less stable Z-product, whereas the E-isomer can be obtained via continuous-flow processing through accurate control of the reaction time. Furthermore, our protocol is amenable to the decarboxylative difluoromethylation of aryl propiolic acids. PMID:29109904

One-pot synthesis of biologically active 1,2,3-trisubstituted pyrrolo[2,3-b]quinoxalines through a palladium-catalyzed reaction with internal alkyne moieties.

PubMed

Keivanloo, Ali; Besharati-Seidani, Tayebeh; Kaboudin, Babak; Yoshida, Akihiro; Yokomatsu, Tsutomu

2018-06-16

Synthesis of 2,3-disubstituted 1-alkylpyrrolo[2,3-b]quinoxalines was accomplished through the reaction of 3-chloroquinoxalin-2-amines with internal alkynes in the presence of Pd(OAc)[Formula: see text], NaOAc, and KOtBu in DMSO. This method afforded desired pyrrolo[2,3-b]quinoxalines in 65-92% reaction yields. The minimum inhibition concentration and minimum bactericidal concentration determinations against Micrococcus luteus and Pseudomonas aeruginosa revealed that some of the synthesized compounds showed the same values compared to tetracycline. These compounds could be used in the future research for the development of new antibiotics.

New antibacterial xanthone from the marine sponge-derived Micrococcus sp. EG45.

PubMed

Eltamany, Enas E; Abdelmohsen, Usama Ramadan; Ibrahim, Amany K; Hassanean, Hashim A; Hentschel, Ute; Ahmed, Safwat A

2014-11-01

Microluside A [4 (19-para-hydroxy benzoyloxy-O-β-D-cellobiosyl), 5 (30-para-hydroxy benzoyloxy-O-β-D-glucopyranosyl) xanthone (1)] is a unique O-glycosylated disubstituted xanthone isolated from the broth culture of Micrococcus sp. EG45 cultivated from the Red Sea sponge Spheciospongia vagabunda. The structure of microluside A was determined by 1D- and 2D-NMR techniques as well as high resolution tandem mass spectrometry. The antimicrobial activity evaluation showed that 1 exhibited antibacterial potential against Enterococcus faecalis JH212 and Staphylococcus aureus NCTC 8325 with MIC values of 10 and 13 μM, respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

[State Oversight in Postsecondary Education and the Office of Education's Eligibility Process. Collected Remarks.

ERIC Educational Resources Information Center

Jung, Steven M.; Proffitt, John

Perspectives on an American Institutes for Research (AIR) study of state oversight in postsecondary education, conducted for the U.S. Office of Education (USOE), are offered by researcher Steven M. Jung. In addition, a list of recommendations by the General Accounting Office concerning USOE's eligibility process and responses by John Proffitt, on…

Defense.gov Special Report: Travels with Winnefeld: USO Tour

Science.gov Websites

Kaneohe Bay - Hawaii Osan Air Base - South Korea CIA Factbook - Diego Garcia Bagram Air Base - Afghanistan Naval Support Activity - Bahrain Naval Support Activity Naples - Italy Ramstein Air Base - Germany Photo Attacked in Seoul Stars Bring Piece of Home to Bagram Airfield During USO Spring Troop Visit Forward Base

Annual Evaluation: Elementary and Secondary Act of 1965 - Title I, Maine, FY 1970.

ERIC Educational Resources Information Center

Maine State Dept. of Education, Augusta.

This evaluation attempts to measure the extent and effectiveness of ESEA Title I programs designed to meet the needs of disadvantaged children and apprizes the public and the legislature of program outcomes. In keeping with USOE requirements for evaluating Title I programs, this document is constructed of (1) responses to USOE probes by…

77 FR 6160 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Approval of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-07

... SLV and USO strike price intervals. \\4\\ The Exchange also proposed certain non-substantive changes to... Strike Price Intervals for SLV and USO Options February 1, 2012. I. Introduction On December 7, 2011...-4 thereunder,\\2\\ a proposed rule change regarding strike price intervals for options on iShares[reg...

COBE navigation with one-way return-link Doppler in the post-helium-venting phase

NASA Technical Reports Server (NTRS)

Dunham, Joan; Nemesure, M.; Samii, M. V.; Maher, M.; Teles, Jerome; Jackson, J.

1991-01-01

The results of a navigation experiment with one way return link Doppler tracking measurements for operational orbit determination of the Cosmic Background Explorer (COBE) spacecraft are presented. The frequency of the tracking signal for the one way measurements was stabilized with an Ultrastable Oscillator (USO), and the signal was relayed by the Tracking and Data Relay Satellite System (TDRSS). The study achieved three objectives: space qualification of TDRSS noncoherent one way return link Doppler tracking; determination of flight performance of the USO coupled to the second generation TDRSS compatible user transponder; and verification of algorithms for navigation using actual one way tracking data. Orbit determination and the inflight USO performance evaluation results are presented.

Synthesis, photophysical, structural and electronic properties of novel regioisomerically pure 1,7-disubstituted perylene-3,4,9,10-tetracarboxylic monoimide dibutylester derivatives

NASA Astrophysics Data System (ADS)

Ozser, Mustafa E.; Mohiuddin, Obaidullah

2018-04-01

Three new isomerically pure 1,7-disubstituted perylene-3,4,9,10-tetracarboxylic monoimide dibutylester derivatives namely; N-[2-(diethylamino)ethyl]-1,7-dibromoperylene-3,4,9,10-tetracarboxy monoimide dibutylester (PMD-1), N-[2-(diethylamino)ethyl]-1,7-di(4-tert-butylphenoxy)perylene-3,4,9,10-tetracarboxy monoimide dibutylester (PMD-2) and N-[2-(diethylamino)ethyl]-1,7-di(pyrrolidinyl)perylene-3,4,9,10-tetracarboxy monoimide dibutylester (PMD-3), have been synthesized and their electronic absorption spectra, and steady-state fluorescence were investigated experimentally as well as by using density functional theory (DFT) calculations. All three compounds show good solubility in toluene and chloroform. Attachment of two tert-butylphenoxy groups at the 1,7-positions in PMD-2 resulted in a red shifted absorption band with an absorption maximum at 518 nm. UV/Vis absorption spectrum of PMD-3 bearing electron donating pyrrolidinyl groups at the 1,7-positions shows a broad absorption band within the visible region, extending to red region. Absorption maximum of lowest energy transition now shifts to 653 nm. In addition to the S0 → S1 absorption bands, bands belonging to S0 → S2 electronic transitions were observed at 378, 386, and 411 nm for PMD-1, PMD-2, and PMD-3 respectively. Compounds PMD-1, PMD-2 and PMD-3 display low fluorescence quantum yields of 0.027, 0.040 and 0.001, respectively in chloroform. DFT calculations revealed that the attachment of electron donating groups at 1,7-positions of perylene core, results in an increase in frontier orbitals energy levels. Observed energy increase in HOMO level is larger in each case, compared to the energy increase in LUMO levels, due to the higher contribution of side groups to HOMO. DFT calculated band gaps for PMD-1, PMD-2 and PMD-3 are 2.68, 2.63 and 2.29 eV respectively.

Mono- and Dinuclear Manganese Carbonyls Supported by 1,8-Disubstituted (L = Py, SMe, SH) Anthracene Ligand Scaffolds.

PubMed

Manes, Taylor A; Rose, Michael J

2016-06-06

Presented herein is a synthetic scheme to generate symmetric and asymmetric ligands based on a 1,8-disubstituted anthracene scaffold. The metal-binding scaffolds were prepared by aryl chloride activation of 1,8-dichloroanthracene using Suzuki-type couplings facilitated by [Pd(dba)2] as a Pd source; the choice of cocatalyst (XPhos or SPhos) yielded symmetrically or asymmetrically substituted scaffolds (respectively): namely, Anth-SMe2 (3), Anth-N2 (4), and Anth-NSMe (6). The ligands exhibit a nonplanar geometry in the solid state (X-ray), owing to steric hindrance between the anthracene scaffold and the coupled aryl units. To determine the flexibility and binding characteristics of the anthracene-based ligands, the symmetric scaffolds were complexed with [Mn(CO)5Br] to afford the mononuclear species [(Anth-SMe2)Mn(CO)3Br] (8) and [(Anth-N2)Mn(CO)3Br] (9), in which the donor moieties chelate the Mn center in a cis fashion. The asymmetric ligand Anth-NSMe (6) binds preferentially through the py moieties, affording the bis-ligated complex [(Anth-NSMe)2Mn(CO)3Br] (10), wherein the thioether-S donors remain unbound. Alternatively, deprotection of the thioether in 6 affords the free thiol ligand Anth-NSH (7), which more readily binds the Mn center. Complexation of 7 ultimately affords the mixed-valence Mn(I)/Mn(II) dimer of formula [(Anth-NS)3Mn2(CO)3] (11), which exhibits a fac-{Mn(CO)3} unit supported by a triad of bridging thiolates, which are in turn ligated to a supporting Mn(II) center (EPR: |D| = 0.053 cm(-1), E/|D| = 0.3, Aiso = -150 MHz). All of the metal complexes have been characterized by single-crystal X-ray diffraction, IR spectroscopy and NMR/EPR measurements-all of which demonstrate that the meta-linked, anthracene-based ligand scaffold is a viable approach for the coordination of metal carbonyls.

Modulation of the Substitution Pattern of 5-Aryl-2-Aminoimidazoles Allows Fine-Tuning of Their Antibiofilm Activity Spectrum and Toxicity

PubMed Central

Peeters, Elien; Hooyberghs, Geert; Robijns, Stijn; Waldrant, Kai; De Weerdt, Ami; Delattin, Nicolas; Liebens, Veerle; Kucharíková, Soňa; Tournu, Hélène; Verstraeten, Natalie; Dovgan, Barbara; Girandon, Lenart; Fröhlich, Mirjam; De Brucker, Katrijn; Michiels, Jan; Cammue, Bruno P. A.; Thevissen, Karin; Vanderleyden, Jozef; Van der Eycken, Erik

2016-01-01

We previously synthesized several series of compounds, based on the 5-aryl-2-aminoimidazole scaffold, that showed activity preventing the formation of Salmonella enterica serovar Typhimurium and Pseudomonas aeruginosa biofilms. Here, we further studied the activity spectrum of a number of the most active N1- and 2N-substituted 5-aryl-2-aminoimidazoles against a broad panel of biofilms formed by monospecies and mixed species of bacteria and fungi. An N1-substituted compound showed very strong activity against the biofilms formed by Gram-negative and Gram-positive bacteria and the fungus Candida albicans but was previously shown to be toxic against various eukaryotic cell lines. In contrast, 2N-substituted compounds were nontoxic and active against biofilms formed by Gram-negative bacteria and C. albicans but had reduced activity against biofilms formed by Gram-positive bacteria. In an attempt to develop nontoxic compounds with potent activity against biofilms formed by Gram-positive bacteria for application in antibiofilm coatings for medical implants, we synthesized novel compounds with substituents at both the N1 and 2N positions and tested these compounds for antibiofilm activity and toxicity. Interestingly, most of these N1-,2N-disubstituted 5-aryl-2-aminoimidazoles showed very strong activity against biofilms formed by Gram-positive bacteria and C. albicans in various setups with biofilms formed by monospecies and mixed species but lost activity against biofilms formed by Gram-negative bacteria. In light of application of these compounds as anti-infective coatings on orthopedic implants, toxicity against two bone cell lines and the functionality of these cells were tested. The N1-,2N-disubstituted 5-aryl-2-aminoimidazoles in general did not affect the viability of bone cells and even induced calcium deposition. This indicates that modulating the substitution pattern on positions N1 and 2N of the 5-aryl-2-aminoimidazole scaffold allows fine-tuning of both the antibiofilm activity spectrum and toxicity. PMID:27550355

Uso de terreno urbano y rural en Puerto Rico

Treesearch

Sebastian Martinuzzi; William A. Gould; Olga M. Ramos Gonzalez; Maya Quinones; Michael E. Jimenez

2008-01-01

El Proyecto de Analisis de Gap de Puerto Rico (PRGAP) (Gould et al. 2008) desarrollo tres usos de terrenos para Puerto Rico: Urbano, Suburbano, y Rural (Martinuzzi et al. 2007). Estas regiones tambien pueden ser consideradas como urbano, densamente-poblado rural, y escasamente-poblado rural, o como urbano y area silvestre con una interfase de area silvestre-urbana. La...

Use of medicines and other products for therapeutic purposes among children in Brazil.

PubMed

Pizzol, Tatiane da Silva Dal; Tavares, Noemia Urruth Leão; Bertoldi, Andréa Dâmaso; Farias, Mareni Rocha; Arrais, Paulo Sergio Dourado; Ramos, Luiz Roberto; Oliveira, Maria Auxiliadora; Luiza, Vera Lucia; Mengue, Sotero Serrate

2016-12-01

To assess the prevalence of the use of medicines and other products for therapeutic purposes in the Brazilian pediatric population and test whether demographic, socioeconomic and health factors are associated with use. A cross-sectional population-based study (National Survey on Access, Use and Promotion of Rational Use of Medicines - PNAUM), including 7,528 children aged 12 or younger, living in urban areas in Brazil. Medicine use to treat chronic or acute diseases was reported by the primary caregiver present at the household interview. Associations between independent variables and medicine use were investigated by Poisson regression. The overall prevalence of medicine use was 30.7% (95%CI 28.3-33.1). The prevalence of medicine use for chronic diseases was 5.6% (95%CI 4.7-6.7) and for acute conditions, 27.1% (95%CI 24.8-29.4). The factors significantly associated with overall use were five years old or under, living in the Northeast region, having health insurance and using health services in the last 12 months (emergency visits and hospitalizations). The following were associated with drug use for chronic diseases: age ≥ 2 years, Southeast and South regions, and use of health services. For drug use in treating acute conditions, the following associated factors were identified: ≤ 5 years, North, Northeast or Midwest regions, health insurance, and one or more emergency visits. The most commonly used drugs among children under two years of age were paracetamol, ascorbic acid, and dipyrone; for children aged two years or over they were dipyrone, paracetamol, and amoxicillin. The use of medicine by children is considerable, especially in treating acute medical conditions. Children using drugs for chronic diseases have a different demographic profile from those using drugs for acute conditions in relation to gender, age, and geographic region. Estimar a prevalência de uso de medicamentos e outros produtos com finalidade terapêutica na população pediátrica brasileira e testar se fatores demográficos, socioeconômicos e médicos estão associados ao uso. Estudo transversal de base populacional (Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos - PNAUM), incluindo 7.528 crianças com 12 anos ou menos de idade, residentes na zona urbana do território brasileiro. O uso de medicamentos para tratar doenças crônicas ou agudas foi referido pelo principal cuidador da criança presente na entrevista domiciliar. Associações entre as variáveis independentes e o uso de medicamentos foram investigadas por meio de regressão de Poisson. A prevalência de uso global de medicamentos foi de 30,7% (IC95% 28,3-33,1). A prevalência de uso de medicamentos para doenças crônicas foi de 5,6% (IC95% 4,7-6,7) e para condições agudas, 27,1% (IC95% 24,8-29,4). Os fatores significativamente associados com o uso global foram ter no máximo cinco anos de idade, residir na região Nordeste, ter plano de saúde e utilizar serviços de saúde nos últimos 12 meses (consultas de emergência e internações). Associaram-se ao uso de medicamentos para doenças crônicas: idade ≥ 2 anos, regiões Sudeste e Sul e utilização de serviços de saúde. Para o uso de medicamentos em condições agudas, foram identificados os seguintes fatores associados: ≤ 5 anos, Norte, Nordeste ou Centro-Oeste, plano de saúde e uma ou mais consultas de emergência. Os medicamentos com maior prevalência de uso pelas crianças menores de dois anos foram paracetamol, ácido ascórbico e dipirona; nas crianças com 2 ou mais anos, foram dipirona, paracetamol e amoxicilina. O uso de medicamentos na população infantil é substancial, principalmente no tratamento de condições médicas agudas. As crianças usuárias de medicamentos para doenças crônicas apresentam perfil demográfico diferente das usuárias de medicamentos para condições agudas, em relação ao sexo, à idade e à região geográfica.

Conceptos Basicos Sobre el Propano (in Spanish)

DOE Office of Scientific and Technical Information (OSTI.GOV)

El propano provee energia a mas de 143.000 vehiculos en los Estados Unidos y 23 millones en todo el mundo. Flotas de todos los Estados Unidos han implementado con exito el uso de vehiculos que funcionan con gas propano, y en la actualidad varios funcionan gracias a este gas, incluyendo autobuses escolares, lanzaderas y autobuses publicos, asi como tambien furgonetas, taxis, vehiculos utilizados por las fuerzas del orden, barredoras de calles y camiones para uso profesional. El propano tambien se utiliza con frecuencia en aplicaciones fuera de la carretera, tales como montacargas, podadoras y equipos de uso profesional y otrosmore » equipos agricolas. Las ventajas del propano incluyen la disponibilidad interna, su rendimiento y el hecho de que genera menos emisiones de gases contaminantes que otras alternativas energeticas.« less

Degradation of 2,4-dichlorophenol using combined approach based on ultrasound, ozone and catalyst.

PubMed

Barik, Arati J; Gogate, Parag R

2017-05-01

The present work investigates the application of ultrasound and ozone operated individually and in combination with catalyst (ZnO and CuO) for establishing the possible synergistic effects for the degradation of 2,4-dichlorophenol. The dependency of extent of degradation on the operating parameters like temperature (over the range of 30-36°C), initial pH (3-9), catalyst as ZnO (loading of 0.025-0.15g/L) and CuO (loading of 0.02-0.1g/L) and initial concentration of 2,4-DCP (20-50ppm) has been established to maximize the efficacy of ultrasound (US) induced degradation. Using only US, the maximum degradation of 2,4-DCP obtained was 28.85% under optimized conditions of initial concentration as 20ppm, pH of 5 and temperature of 34°C. Study of effect of ozone flow rate for approach of only ozone revealed that maximum degradation was obtained at 400mg/h ozone flow rate. The combined approaches such as US+O 3 , US+ZnO, US+CuO, O 3 +ZnO, O 3 +CuO, US+O 3 +ZnO and US+O 3 +CuO have been subsequently investigated under optimized conditions and observed to be more efficient as compared to individual approaches. The maximum extent of degradation for the combined operation of US+O 3 (400mg/h)+ZnO (0.1g/L) and US+O 3 (400mg/h)+CuO (0.08g/L) has been obtained as 95.66% and 97.03% respectively. The degradation products of 2,4-DCP have been identified using GC-MS analysis and the toxicity analysis has also been performed based on the anti-microbial activity test (agar-well diffusion method) for the different treatment strategies. The present work has conclusively established that the combined approach of US+O 3 +CuO was the most efficient treatment scheme resulting in near complete degradation of 2,4-DCP with production of less toxic intermediates. Copyright © 2016 Elsevier B.V. All rights reserved.

Biosynthesis in vitro of Caenorhabditis elegans phosphorylcholine oligosaccharides

PubMed Central

Cipollo, John F.; Awad, Antoine; Costello, Catherine E.; Robbins, Phillips W.; Hirschberg, Carlos B.

2004-01-01

The biosynthesis in vitro of phosphorylcholine oligosaccharides in Caenorhabditis elegans has been investigated. Here we show that extracts of C. elegans' microsomes transfer phosphorylcholine from L-α-dipalmitoyl phosphatidylcholine to hybrid and complex type N-linked oligosaccharides containing mannose residues disubstituted with N-acetylglucosamine. The reaction products are consistent with structures reported for C. elegans as well those found in the filarial nematodes Acanthocheilonema viteae, Onchocerca volvulus, and Brugia malayi, strongly supporting the concept that the phosphorylcholine oligosaccharide biosynthetic enzymes are conserved in this group of organisms. Because it is thought that phosphorylcholine substitution of oligosaccharides modulates host immune response in filarial infections, this in vitro system may help in gaining an understanding of the basis for this response. PMID:14993596

Synthesis and biological activity of pyrrole analogues of combretastatin A-4.

PubMed

Jung, Eun-Kyung; Leung, Euphemia; Barker, David

2016-07-01

A series of pyrrole analogues of combretastatin (CA-4) were synthesized and tested for their anti-proliferative activity. The highly diastereoselective acyl-Claisen rearrangement was used to provide 2,3-syn disubstituted morpholine amides which were used as precursors for the various analogues. This synthesis allows for the preparation of 1,2- and 2,3-diaryl-1H-pyrroles which are both geometrically similar to CA-4. These pyrrolic analogues were tested for their anti-proliferative activity against two human cell lines, K562 and MDA-MB-231 with 2,3-diaryl-1H-pyrrole 35 exhibiting the most potent activity with IC50 value of 0.07μM against MDA-MB-231 cell line. Copyright © 2016 Elsevier Ltd. All rights reserved.

Regioselective and enantiospecific rhodium-catalyzed allylic alkylation reactions using copper(I) enolates: synthesis of (-)-sugiresinol dimethyl ether.

PubMed

Evans, P Andrew; Leahy, David K

2003-07-30

The transition metal-catalyzed allylic alkylation represents a fundamentally important cross-coupling reaction for the construction of ternary carbon stereogenic centers. We have developed a regioselective and enantiospecific rhodium-catalyzed allylic alkylation of acyclic unsymmetrical allylic alcohol derivatives using copper(I) enolates to prepare beta-substituted ketones. This protocol represents a convenient asymmetric Claisen rearrangement surrogate in which alpha-substituted enolates permit the introduction of an additional stereogenic center. The synthetic utility of this transformation was highlighted in the construction of a trans-1,2-disubstituted cyclohexene and the total synthesis of (-)-sugiresinol dimethyl ether. Finally, we anticipate that copper(I) enolates may prove useful nucleophiles in related metal-catalyzed reactions.

Homologation Reaction of Ketones with Diazo Compounds.

PubMed

Candeias, Nuno R; Paterna, Roberta; Gois, Pedro M P

2016-03-09

This review covers the addition of diazo compounds to ketones to afford homologated ketones, either in the presence or in the absence of promoters or catalysts. Reactions with diazoalkanes, aryldiazomethanes, trimethylsilyldiazomethane, α-diazo esters, and disubstituted diazo compounds are covered, commenting on the complex regiochemistry of the reaction and the nature of the catalysts and promoters. The recent reports on the enantioselective version of ketone homologation reactions are gathered in one section, followed by reports on the use of cyclic ketones ring expansion in total synthesis. Although the first reports of this reaction appeared in the literature almost one century ago, the recent achievements, in particular, for the asymmetric version, forecast the development of new breakthroughs in the synthetically valuable field of diazo chemistry.

One-Pot Amide Bond Formation from Aldehydes and Amines via a Photoorganocatalytic Activation of Aldehydes.

PubMed

Papadopoulos, Giorgos N; Kokotos, Christoforos G

2016-08-19

A mild, one-pot, and environmentally friendly synthesis of amides from aldehydes and amines is described. Initially, a photoorganocatalytic reaction of aldehydes with di-isopropyl azodicarboxylate leads to an intermediate carbonyl imide, which can react with a variety of amines to afford the desired amides. The initial visible light-mediated activation of a variety of monosubstituted or disubstituted aldehydes is usually fast, occurring in a few hours. Following the photocatalytic reaction, addition of the primary amine at room temperature or the secondary amine at elevated temperatures leads to the corresponding amide from moderate to excellent yields without epimerization. This methodology was applied in the synthesis of Moclobemide, a drug against depression and social anxiety.

Applicability of common stomatal conductance models in maize under varying soil moisture conditions.

PubMed

Wang, Qiuling; He, Qijin; Zhou, Guangsheng

2018-07-01

In the context of climate warming, the varying soil moisture caused by precipitation pattern change will affect the applicability of stomatal conductance models, thereby affecting the simulation accuracy of carbon-nitrogen-water cycles in ecosystems. We studied the applicability of four common stomatal conductance models including Jarvis, Ball-Woodrow-Berry (BWB), Ball-Berry-Leuning (BBL) and unified stomatal optimization (USO) models based on summer maize leaf gas exchange data from a soil moisture consecutive decrease manipulation experiment. The results showed that the USO model performed best, followed by the BBL model, BWB model, and the Jarvis model performed worst under varying soil moisture conditions. The effects of soil moisture made a difference in the relative performance among the models. By introducing a water response function, the performance of the Jarvis, BWB, and USO models improved, which decreased the normalized root mean square error (NRMSE) by 15.7%, 16.6% and 3.9%, respectively; however, the performance of the BBL model was negative, which increased the NRMSE by 5.3%. It was observed that the models of Jarvis, BWB, BBL and USO were applicable within different ranges of soil relative water content (i.e., 55%-65%, 56%-67%, 37%-79% and 37%-95%, respectively) based on the 95% confidence limits. Moreover, introducing a water response function, the applicability of the Jarvis and BWB models improved. The USO model performed best with or without introducing the water response function and was applicable under varying soil moisture conditions. Our results provide a basis for selecting appropriate stomatal conductance models under drought conditions. Copyright © 2018 Elsevier B.V. All rights reserved.

Sociodemographic and Substance Use Disorder Determinants of HIV Sexual Risk Behavior in Men and Women in Outpatient Drug Treatment in the NIDA National Drug Abuse Treatment Clinical Trials Network.

PubMed

Kidd, Jeremy D; Tross, Susan; Pavlicova, Martina; Hu, Mei-Chen; Campbell, Aimee N C; Nunes, Edward V

2017-06-07

Sexual risk behavior is now the primary vector of HIV transmission among substance users in the United States with gender as a crucial moderator of risk behavior. The purpose of this study was to examine gender differences in factors (age, race/ethnicity, education) that predict main-partner unprotected sexual occasions (USO) using the unique platform of two parallel NIDA National Drug Abuse Treatment Clinical Trials Network gender-specific safer sex intervention trials. Baseline assessments of male (N = 430) and female (N = 377) participants included demographic characteristics; past 3-month sexual activity; and a diagnostic assessment for alcohol, cocaine/stimulant, and opioid use disorders. Using mixed effects generalized linear modeling of the main outcome USO, two-way interactions of gender with age, race/ethnicity, and education were evaluated and adjusted by alcohol, cocaine/stimulant, or opioid use disorder. When adjusted for alcohol use disorder, the interaction of education and gender was significant. For men, a high school or greater education was significantly associated with more USO compared to men with less than high school. For women, greater than high school education was significantly associated with less USO compared to women with a high school education. None of the other interactions were significant when adjusted for cocaine/stimulant or opioid use disorder. Conclusions/Importance: This study demonstrates gender differences in the relationship of education, alcohol use disorder, and main-partner USO in individuals in substance abuse treatment. This underscores the importance of considering demographic and substance use factors in HIV sexual risk behavior and in crafting prevention messages for this population.

Photoinduced Bioorthogonal 1,3-Dipolar Poly-cycloaddition Promoted by Oxyanionic Substrates for Spatiotemporal Operation of Molecular Glues.

PubMed

Hatano, Junichi; Okuro, Kou; Aida, Takuzo

2016-01-04

PGlue(PZ), a pyrazoline (PZ)-based fluorescent adhesive which can be generated spatiotemporally in living systems, was developed. Since PGlue(PZ) carries many guanidinium ion (Gu(+)) pendants, it strongly adheres to various oxyanionic substrates through a multivalent salt-bridge interaction. PGlue(PZ) is given by bioorthogonal photopolymerization of a Gu(+)-appended monomer (Glue(TZ)), bearing tetrazole (TZ) and olefinic termini. Upon exposure to UV light, Glue(TZ) transforms into a nitrileimine (NI) intermediate (Glue(NI)), which is eligible for 1,3-dipolar polycycloaddition. However, Glue(NI) in aqueous media can concomitantly be deactivated into Glue(WA) by the addition of water, and the polymerization hardly occurs unless Glue(NI) is concentrated. We found that, even under high dilution, Glue(NI) is concentrated on oxyanionic substrates to a sufficient level for the polymerization, so that their surfaces can be point-specifically functionalized with PGlue(PZ) by the use of a focused beam of UV light. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Predicting Trigger Bonds in Explosive Materials through Wiberg Bond Index Analysis.

PubMed

Harper, Lenora K; Shoaf, Ashley L; Bayse, Craig A

2015-12-21

Understanding the explosive decomposition pathways of high-energy-density materials (HEDMs) is important for developing compounds with improved properties. Rapid reaction rates make the detonation mechanisms of HEDMs difficult to understand, so computational tools are used to predict trigger bonds-weak bonds that break, leading to detonation. Wiberg bond indices (WBIs) have been used to compare bond densities in HEDMs to reference molecules to provide a relative scale for the bond strength to predict the activated bonds most likely to break to trigger an explosion. This analysis confirms that X-NO2 (X=N,C,O) bonds are trigger linkages in common HEDMs such as TNT, RDX and PETN, consistent with previous experimental and theoretical studies. Calculations on a small test set of substituted tetrazoles show that the assignment of the trigger bond depends upon the functionality of the material and that the relative weakening of the bond correlates with experimental impact sensitivities. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A copper-phosphonate network as a high-performance heterogeneous catalyst for the CO2 cycloaddition reactions and alcoholysis of epoxides.

PubMed

Ai, Jing; Min, Xue; Gao, Chao-Ying; Tian, Hong-Rui; Dang, Song; Sun, Zhong-Ming

2017-05-23

A novel 3D copper-phosphonate network, with the general formula Cu 7 (H 1 L) 2 (TPT) 3 (H 2 O) 6 , namely compound 1, has been synthesized using a rigid tetrahedral linker tetraphenylsilane tetrakis-4-phosphonic acid (H 8 L) and a nitrogen-containing ancillary ligand (TPT: [5-(4-(1H-1,2,4-triazol-1-yl)phenyl)-1H-tetrazole]) under hydrothermal conditions. The compound was fully characterized using PXRD, ICP, IR, TGA and elemental analysis. Compound 1 can be used as an efficient catalyst for the CO 2 coupling reaction that is greatly superior to many conventional MOF-based catalysts, where porosity is always mentioned and used. In addition, it shows excellent catalytic performance for ring-opening reactions with epoxides under ambient conditions. Additionally, compound 1 can be recycled at least three times without a significant compromise in the activity in the two catalytic reactions.

Cytoprotective effect of Valeriana officinalis extract on an in vitro experimental model of Parkinson disease.

PubMed

de Oliveria, Diêgo Madureira; Barreto, George; De Andrade, Deyse Valverde G; Saraceno, Ezequiel; Aon-Bertolino, Laura; Capani, Francisco; Dos Santos El Bachá, Ramon; Giraldez, Lisandro Diego

2009-02-01

Parkinson's disease (PD) is one of the most important neurodegenerative worldwide disorders. The potential cytoprotective effects of aqueous extract of Valeriana officinalis on rotenone-induced apoptosis in human neuroblastoma SH-SY5Y cells were demonstrated. The cytotoxicity, cell viability and analysis of cellular morphology were performed by MTT-tetrazole (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and phase contrast microscopy, respectively. Significant changes in the cellular morphology, and condensation of the cell body could be observed when cells were treated with 300 nM rotenone for 48 h. Three different concentrations of Valeriana officinalis extract were used (0.049, 0.098 and 0.195 mg/mL). These extracts brought about an increase of 7.0 +/- 1.3%, 14.5 +/- 1.3% and 14.5 +/- 3.2% in cell viability. Our results indicated that neuroprotector action of the Valeriana officinalis extract provides support for later studies as they help understanding this drug for the development of cytoprotective various therapies in PD.

Bis(azido) compounds of Pd and Pt with bulky phosphine ligands (dppn=1,8-bis(diphenylphosphino)naphthalene, dppf=1,1‧-bis(diphenylphosphino)ferrocene, 1-dpn=1-diphenylphosphino-naphthalene): Preparation, structures, and reactivity toward isocyanides

NASA Astrophysics Data System (ADS)

Huh, Hyun Sue; Lee, Yeon Kyoung; Lee, Soon W.

2006-05-01

Pd-bis(azido) compounds [Pd(dppn)(N 3) 2] and [Pd(dppf)(N 3) 2], which contain bulky chelating bis(phosphine) ligands (dppn=1,8-bis(diphenylphosphino)naphthalene, dppf=1,1'-bis(diphenylphosphino)ferrocene), were prepared from the corresponding chlorides and NaN 3. We also prepared the Pt-bis(azido) compound [Pt(1-dpn)(SMe 2)(N 3) 2] containing a bulky monodentate phosphine (1-dpn=1-diphenylphosphino-naphthalene). All these compounds underwent [2+3] cycloaddition with isocyanides (R-NC, R=cyclohexyl, tert-butyl, 2,6-dimethylphenyl) to convert azido ligands to five-membered, C-coordinated tetrazolate rings. In addition, we observed the [Pd(dppn)Cl 2]-mediated C-C coupling of PhC tbnd6 CH to generate the η 2-PhC tbnd6 C-C tbnd6 CPh ligand. All compounds have been structurally characterized by X-ray diffraction.

[Trattamento farmacologico del disturbo da uso di alcol. Evidenze scientifiche].

PubMed

Attilia, Fabio; Perciballi, Roberta; Rotondo, Claudia; Capriglione, Ida; Iannuzzi, Silvia; Attilia, Maria Luisa; Vitali, Mario; Alessandrini, Giovanni; Scamporrino, Maria Concetta Marcella; Fiore, Marco; Ceccanti, Mauro

2018-01-01

RIASSUNTO. La terapia farmacologica nei pazienti con disturbo da uso di alcol riveste un ruolo centrale nel progetto terapeutico, altamente contestualizzato in un approccio multidisciplinare. Sebbene i trattamenti non farmacologici per la dipendenza da alcol risultino ben strutturati e in continua evoluzione, dal punto di vista medico le possibilità di intervento sono realmente ristrette, con poche molecole a disposizione approvate per il disturbo da uso di alcol: nello specifico, l'acamprostato, il naltrexone e, più recentemente, il nalmefene tra gli anticraving; il disulfiram tra gli avversivanti. Nuovi approcci sperimentali stanno cercando di ampliare tale gamma attraverso l'utilizzo di farmaci off-label. Evidenze scientifiche devono supportare l'indicazione terapeutica, quest'ultima deve dimostrarsi "cucita" sulle esigenze del paziente e sulle comorbilità presenti tenendo conto del profilo bio-psico-sociale individuale. Fondamentale risulta il follow-up per valutare la ritenzione in trattamento e il monitoraggio degli outcome alcologici.

Substituted polyacetylene separation membrane

DOEpatents

Pinnau, Ingo; Morisato, Atsushi

1998-01-13

A separation membrane useful for gas separation, particularly separation of C.sub.2+ hydrocarbons from natural gas. The invention encompasses the membrane itself, methods of making it and processes for using it. The membrane comprises a polymer having repeating units of a hydrocarbon-based, disubstituted polyacetylene, having the general formula: ##STR1## wherein R.sub.1 is chosen from the group consisting of C.sub.1 -C.sub.4 alkyl and phenyl, and wherein R.sub.2 is chosen from the group consisting of hydrogen and phenyl. In the most preferred embodiment, the membrane comprises poly(4-methyl-2-pentyne) ›PMP!. The membrane exhibits good chemical resistance and has super-glassy properties with regard to separating certain large, condensable permeant species from smaller, less-condensable permeant species. The membranes may also be useful in other fluid separations.

From indole to pyrrole, furan, thiophene and pyridine: Search for novel small molecule inhibitors of bacterial transcription initiation complex formation.

PubMed

Thach, Oscar; Mielczarek, Marcin; Ma, Cong; Kutty, Samuel K; Yang, Xiao; Black, David StC; Griffith, Renate; Lewis, Peter J; Kumar, Naresh

2016-03-15

The search for small molecules capable of inhibiting transcription initiation in bacteria has resulted in the synthesis of N,N'-disubstituted hydrazines and imine-carbohydrazides comprised of indole, pyridine, pyrrole, furan and thiophene using the respective trichloroacetyl derivatives, carbohydrazides and aldehydes. Replacement of the indole moiety by smaller heterocycles linked by CONHNC linkers afforded a broad variety of compounds efficiently targeting the RNA polymerase-σ(70)/σ(A) interaction as determined by ELISA and exhibiting increased inhibition of the growth of Escherichia coli compared to Bacillus subtilis in culture. The structural features of the synthesized transcription initiation inhibitors needed for antibacterial activity were identified employing molecular modelling and structure-activity relationship (SAR) studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Dual Anticancer Efficacy Molecule: A Selective Dark Cytotoxicity Photosensitizer.

PubMed

Chen, Jyun-Wei; Chang, Cheng-Chung

2016-11-09

Unlike traditional binary nanostructures that construct chemotherapy drugs and photodynamic therapy photosensitizers, we introduce a molecule with a chemo-photodynamic dual therapy function. A water-soluble aggregation-induced emission enhancement (AIEE) fluorogen, NV-12P, was designed and synthesized based on asymmetric 1,6-disubstituted naphthalene and can generate particular reactive oxygen species to undergo type I photodynamic therapy under irradiation. Furthermore, this compound can specifically localize in mitochondria and, after biological evaluation, can cause mitochondrial dysfunction and potent cytotoxicity to cancer cells but not normal cells. We conclude that this compound is a potential dual-toxic efficacy molecule because it exhibits selective dark cytotoxicity and efficient photodamage in cancer cells. Additionally, we also supported the optimal combinational treatment course for the best chemo-phototherapy efficacy.

Quadratic response functions in the relativistic four-component Kohn-Sham approximation

NASA Astrophysics Data System (ADS)

Henriksson, Johan; Saue, Trond; Norman, Patrick

2008-01-01

A formulation and implementation of the quadratic response function in the adiabatic four-component Kohn-Sham approximation is presented. The noninteracting reference state is time-reversal symmetric and formed from Kramers pair spinors, and the energy density is gradient corrected. Example calculations are presented for the optical properties of disubstituted halobenzenes in their meta and ortho conformations. It is demonstrated that correlation and relativistic effects are not additive, and it is shown that relativity alone reduces the μβ¯-response signal by 62% and 75% for meta- and ortho-bromobenzene, respectively, and enhances the same response by 17% and 21% for meta- and ortho-iodobenzene, respectively. Of the employed functionals, CAM-B3LYP shows the best performance and gives hyperpolarizabilities β distinctly different from B3LYP.

Application of the ultrasound in the mild synthesis of substituted 2,3-dihydroquinazolin-4(1H)-ones catalyzed by heterogeneous metal-MWCNTs nanocomposites

NASA Astrophysics Data System (ADS)

Safari, Javad; Gandomi-Ravandi, Soheila

2014-08-01

A practical method were applied successfully to synthesize mono- and disubstituted dihydroquinazolinones through three-component condensation of isatoic anhydride, primary amines or ammonium acetate with aromatic aldehydes in the presence of some transition metals-multi-walled carbon nanotubes under sonication. Also, metals supported on MWCNTs showed excellent catalytic performance for above-mentioned condensation. This methodology provides general, easy and efficient approach to afford the corresponding aryl substituted quinazolinone derivatives using mentioned nanocomposites as catalyst under sonication in excellent yields. The advantages of present protocol are convenient reaction, simple work-up, greenness, energy efficiency and reusable catalyst as well as mild reaction conditions. The employed metal-MWCNTs catalysts are heterogeneous and recyclable, that make the process more environmentally friendly.

Rim-Differentiated C5-Symmetric Tiara-Pillar[5]arenes

PubMed Central

2017-01-01

The synthesis of “rim-differentiated” C5-symmetric pillar[5]arenes, whose two rims are decorated with different chemical functionalities, has remained a challenging task. This is due to the inherent statistical nature of the cyclization of 1,4-disubstituted alkoxybenzenes with different substituents, which leads to four constitutional isomers with only 1/16th being rim-differentiated. Herein, we report a “preoriented” synthetic protocol based on FeCl3-catalyzed cyclization of asymmetrically substituted 2,5-dialkoxybenzyl alcohols. This yields an unprecedented 55% selectivity of the C5-symmetric tiara-like pillar[5]arene isomer among four constitutional isomers. Based on this new method, a series of functionalizable tiara-pillar[5]arene derivatives with C5-symmetry was successfully synthesized, isolated, and fully characterized in the solid state. PMID:29220153

A Convergent, Modular Approach to Functionalized 2,1-Borazaronaphthalenes from 2-Aminostyrenes and Potassium Organotrifluoroborates

PubMed Central

Wisniewski, Steven R.; Guenther, Courtney L.; Argintaru, O. Andreea; Molander, Gary A.

2014-01-01

Azaborines are an important class of compounds with applications in both medicinal chemistry and materials science. 2-Chloro-2,1-borazaronaphthalene was the first borazaronaphthalene reported in 1959; however, access to more highly functionalized substructures has been limited because of the harsh reaction conditions required to displace the chloride on boron. A convergent approach has been developed to synthesize disubstituted 2,1-borazaronaphthalenes from N-substituted 2-aminostyrenes and potassium organotrifluoroborates, where the potassium organotrifluoroborate is converted to the active R-BX2 species (X = Cl or F) in situ by addition of a fluorophile. Starting from aryl-, heteroaryl-, alkynyl-, alkenyl-, and alkyltrifluoroborates, a library of highly functionalized 2,1-borazaronaphthalenes are synthesized in one step under mild, transition-metal free conditions. PMID:24328074