Azole Heterocycles Research Articles

Synthesis, Structure, Spectroscopic Properties, and Antiproliferative Activity In Vitro of Novel Osmium(III) Complexes with Azole Heterocycles

Reactions of (H 2azole) 2[OsCl 6], where Hazole = pyrazole, Hpz, ( 1), indazole, Hind, ( 2), imidazole, Him, ( 3) and benzimidazole, Hbzim, ( 4) with the corresponding azole heterocycle in 1:4 molar ratio in boiling isoamyl alcohol or hexanol-1 afforded novel water-soluble osmium(III) complexes of the type trans-[OsCl 2(Hazole) 4]Cl, where Hazole = Hpz ( 5a), Hind ( 6a), Him ( 7a), and Hbzim ( 9a) in 50-70% ( 5a, 7a, 9a) and 5% ( 6a) yields. The synthesis of 7a was accompanied by a concurrent reaction which led to minor formation (<4%) of cis-[OsCl 2(Him) 4]Cl ( 8). The complexes were characterized by elemental analysis, IR spectroscopy, UV-vis spectroscopy, ESI mass spectrometry, cyclic voltammetry, and X-ray crystallography. 5a, 7a, and 9a were found to possess remarkable antiproliferative activity in vitro against A549 (non-small cell lung carcinoma), CH1 (ovarian carcinoma), and SW480 (colon carcinoma) cells, which was compared with that of related ruthenium compounds trans-[RuCl 2(Hazole) 4]Cl, where Hazole = Hpz (5b), Hind (6b), Him (7b), and Hbzim (9b).

Catalytic aza-Wittig Cyclizations for Heteroaromatic Synthesis

The first examples of heterocycle synthesis by iminophosphorane formation/intramolecular aza-Wittig cyclizations that are catalytic in the organophosphorus component are reported. The reaction has been demonstrated in the synthesis of both azine (phenanthridine) and azole (benzoxazole) heterocycles. Catalyst loadings down to 1 mol % have been used with little or no loss in reaction efficiency. The intimate involvement of the phosphine oxide in the catalytic cycle has been verified by in situ infrared spectroscopy.

Novel Ag(I) complexes with azole heterocycle ligands bearing acetic acid group: synthesis, characterization and crystal structures

Download options Please wait... Supplementary files Crystal structure data CIF (46K) Crystal structure data TXT (46K) Article information DOI https://doi.org/10.1039/B801070F Article type Paper Submitted 21 Jan 2008 Accepted 07 Apr 2008 First published 09 May 2008 Download Citation CrystEngComm, 2008,10, 1037-1043 BibTex EndNote MEDLINE ProCite ReferenceManager RefWorks RIS Permissions Request permissions Novel Ag(I) complexes with azole heterocycle ligands bearing acetic acid group: synthesis, characterization and crystal structures T. Hu, W. Du, B. Hu, J. Li, X. Bu and R. Cao, CrystEngComm, 2008, 10, 1037 DOI: 10.1039/B801070F To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page. If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given. If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page. Read more about how to correctly acknowledge RSC content. Social activity Tweet Share Search articles by author Tong-Liang Hu Wen-Ping Du Bo-Wen Hu Jian-Rong Li Xian-He Bu Rong Cao

Reaction of Azole Heterocycles with Tris(dimethylamino)borane, a New Method for the Construction of Tripodal Borate‐Centred Ligands

Reaction of 2-mercapto-1-methylimidazole (methimazole) with tris(dimethylamino)borane, B(NMe2)3, provides the tetrahedral dimethylamine adduct of tris(methimazolyl)borane, [(Me2HN)B(methimazolyl)3]. By contrast, imidazole, 2-methylimidazole, 2-chloroimidazole and benzimidazole provide the homoleptic tetra-azolyl systems H[B(azolyl)4], and the same product is obtained even when a substoichiometric quantity of the heterocyle is employed. The change in reaction outcome is correlated with the variation of basic pKa for the heterocycles. A simple acid-base reaction with elimination of HNMe2 is proposed for the reaction with the weakly basic, but more strongly acidic, methimazole. However, for the more strongly basic imidazoles, initial coordination of the heterocycle imine nitrogen to the weakly Lewis acidic boron centre in B(NMe2)3 to form the tetrahedral adduct [(azole)B(NMe2)3] is proposed. The greater availability of the NMe2 lone pairs in this species results in increased basicity and a rapid reaction with further heterocycle to provide the observed H[B(azolyl)4] products. For 2-nitroimidazole, the low basicity (and increased N-H acidity) results in the formation of [(HNMe2)B(2-nitroimidazolyl)3] on reaction with B(NMe2)3, analogous to the product formed with methimazole. Both [(HNMe2)B(methimazolyl)3] and H[B(benzimidazolyl)4] have been structurally characterised by single crystal X-ray crystallography. This chemistry has been exploited to provide a new synthesis of borate-centred tripod ligands, whereby N-methylimidazole is used to activate B(NMe2)3 to reaction with methimazole to form the new ligand [(N-methylimidazole)B(methimazolyl)3] in good yield and a complex of this ligand with Ru(II) has been structurally characterised.

Dependence of the carcinogenicity of nitric compounds on their structural characteristics

A new approach to the description of quantitative structure-activity relationships (QSAR analysis) based on compound descriptors has been used. The effect of the structural characteristics of nitric compounds on their carcinogenicity has been studied. It has been found that the carcinogenicity of nitric compounds is determined by the presence of furyl and/or azole heterocycles not condensed with benzene rings in their molecular structures. The carcinogenicity of the nitric compounds in which the benzene ring is the basic structure is determined by the presence of other substituents (halogens, amines, and methyl groups) and their positions relative to the nitro group.

Thermal latent coordination compounds

Complexes of the type M(Pa) 2 (HAz) 2 and M(QA) 2 (HAz) 2 (M=cobalt(II) and nickel(II); HPa=picolinic acid, HQa=quinaldic acid; HAz=azoles like imidazole (HIm), pyrazole (HPz), benzimidazole (HBzIm) etc.) show a similar thermal behaviour. In the first step of decomposition the corresponding azolinium picolinates or quinaldinates (H 2 AzPa, H 2 AzQa) are split off with formation of polymeric mixed ligand complexes M(Pa)(Az) or M(Qa)(Az). X-ray analysis of Co(Qa) 2 (HBzIm ) 2 XIIIa illustrates a proton transfer and a subsequent thermal removal of benzimidazolinium quinaldinate (H 2 BzImQa) : Hydrogen bridges from pyrrole nitrogen of the benzimidazole to the non-coordinated oxygen of the quinaldinate predetermine the thermal initiated proton transfer. The high volatility of the heterocyclic acids and the nitrogen coordination are responsible for the formation of the mixed ligand complex Co(Qa)(BzIm) XIVa. Exceptions are the complexes M(Pa) 2 (HPz) 2 XIa-b and M(Qa) 2 (HIm) 2 XVIIa-b. Pyrazole is eliminated from the complexes XIa-b with formation of the solvent-free inner complex M(Pa) 2 XIIa-b. From compounds XVIIIa-b quinaldic acid or their decomposition products are split off and a high temperature modification of M(Im) 2 XVIIIa-b is formed at elevated temperature. XVIIIa-b are decomposed to the cyanides M(CN) 2 similarly to the thermal behaviour of Cu(Im). In the first step the thermal degradation of imidazole and pyrazole adducts of copper(II) picolinates and quinaldinates is characterized by the elimination ofazoles. The reason for this thermal behaviour-is the weaker coordination ofthe azole heterocycles in copper chelate compounds.

Differential expression of microsomal epoxide hydrolase gene by azole heterocycles in rats

The effects of heterocycles including imidazole (IM), 1,2,4-triazole (TR) and thiazole (TH) on the expression of microsomal epoxide hydrolase (mEH) gene were examined in rats (200 mg kg body weight day , i.p.). Hepatic microsomes prepared from rats treated with IM for 3 days failed to exhibit an increase in mEH protein level whereas TR treatment resulted in an approximately 2- to 3- fold levation in hepatic mEH levels relative to control, as assessed by both SDS-PAGE and immunoblot analyses. In contrast, thiazole-induced hepatic microsomes resulted in a substantial increase in mEH levels (i.e.∼5-fold). Slot and northern blot analyses, probed with an mEH cDNA, showed that the hepatic mEH mRNA levels in the animals treated with IM for 3 days were marginally increased by ∼2-fold, as compared with untreated animals, whereas TR caused an ∼8-fold increase in hepatic mEH mRNA levels after three consecutive daily treatments. TH treatment resulted in an ∼22-fold increase in the mEH mRNA levels, demonstrating that TH is the most efficacious among these three azole heterocycles. Because TH was the most effective in increasing hepatic mEH protein and mRNA levels, the agent was chosen for further evaluation. Time course of mEH gene expression at early times after a single treatment with TH was determined and compared with that caused by pyrazine (PZ), a strong mEH inducer. Hepatic mEH mRNA levels were increased ∼1-, 3-, 20- and 16-fold at 3, 6, 12 and 24 hr, respectively, following TH treatment, relative to control, whereas mEH mRNA levels were elevated ∼1-, 1-, 22- and 18-fold, respectively, at the same time points after PZ treatment, as monitored by slot RNA hybridization analyses. Northern blot analyses using either total RNA or poly(A) + RNA fractions exhibited comparable time courses in increasing mEH mRNA levels after TH or PZ treatment with maximal mRNA increases being noted at 12 hr post treatment. Although neither IM or TR failed to affect renal mEH gene expression to a notable extent, TH treatment caused 6- to 8-fold increases in kidney mEH mRNA levels, with a 2-fold increase in mEH protein detected. These results demonstrated that the azole heterocyclic compounds IM, TR and TH differentially induce mEH with TH as the most efficacious azole; and that the changes in mEH levels are primarily associated with increases in mRNA levels.