1,3-Dipolar cycloaddition of nitrile oxides to (R)-1-(1-phenylethyl)-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones: synthesis and antimycobacterial evaluation of novel enantiomerically pure di- and trispiroheterocycles

Enantiomerically pure (R)-(1-phenylethyl)-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones were synthesized for the first time, and their 1,3-dipolar cycloaddition with nitrile oxides affording di- and trispiroheterocycles regio- and stereoselectively in moderate yields was investigated. These compounds were evaluated against Mycobacterium tuberculosis H37Rv (MTB) and multi-drug-resistant M. tuberculosis (MDR-TB). Among the compounds screened, the dispiroheterocycle, namely, (5R,6R,10S)-3,9-bis(4-chlorophenyl)-10-(2,4-dichlorophenyl)-14-[(E)-(2,4-dichlorophenyl)methylidene]-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-tri-azadispiro[4.0.4.4]tetradeca-2,8-diene 5m was found to possess the maximum activity with MIC of 0.49 μM against MTB, being 9.6 and 15.6 times more potent than ciprofloxacin and ethambutol, respectively. Against MDR-TB, 5m displayed maximum activity with an MIC of 0.49 μM, with it thus being more active than rifampicin, isoniazid, ciprofloxacin and ethambutol by 7.8, 23, 77 and 124 times, respectively.     

Optical, dielectric and microhardness studies on 1 0 0 directed ADP crystal

1 0 0 directed ammonium dihydrogen phosphate single crystal has been grown using the uniaxially solution-crystallization method of Sankaranarayanan–Ramasamy (SR). The size of the grown crystal is 40 mm in diameter and 50 mm in thickness. The grown crystals were characterized by UV–vis spectroscopy, Vickers hardness and dielectric studies. Comparing the 1 0 0 plane of the conventional method grown ADP crystal with 1 0 0 directed SR method grown ADP crystal, optical transparency, dielectric constant and Vickers hardness number are increased and dielectric loss is decreased in SR method grown crystal.     

Oxidative degradation and deamination of atenolol by diperiodatocuprate(III) in aqueous alkaline medium: A mechanistic study

The kinetics of oxidation of atenolol (ATN) by diperiodatocuprate(III) (DPC) in aqueous alkaline medium at a constant ionic strength of 0.10 mol dm⁻³ was studied spectrophotometrically. The reaction between DPC and ATN in alkaline medium exhibits 1:2 stoichiometry (ATN:DPC). The reaction is of first order in [DPC] and has less than unit order in both [ATN] and [alkali]. However, the order in [ATN] and [alkali] changes from first order to zero order as their concentration increase. Intervention of free radicals was observed in the reaction. Increase in periodate concentration decreases the rate. The oxidation reaction in alkaline medium has been shown to proceed via a monoperiodatocuprate(III)–ATN complex, which decomposes slowly in a rate-determining step followed by other fast steps to give the products. The main oxidative products were identified by spot test, IR, NMR and LC–ESI-MS studies. The reaction constants involved in the different steps of the mechanism are calculated. The activation parameters with respect to slow step of the mechanism are computed and discussed, and thermodynamic quantities are also determined.     

Synthesis,characterization and pharmacological evaluation of some new 1,3,4-oxadiazole derivatives bearing 3-chloro-2-fluoro phenyl moiety

A new series of 2-(3-chloro-2-fluorophenyl)-5-aryl-1,3,4-oxadiazole (3a–j) and 2-(aryl sulfanyl)-5-(3-chloro-2-fluorophenyl)-1,3,4-oxadiazole (5a–e) were synthesized via a multistep reaction from 3-chloro-2-fluoro benzoic acid. The newly synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, mass spectral data and elemental analysis. They were also screened for their in vivo anti-convulsant and anti-inflammatory activities. Some of them exhibited significant biological activities and were well supported by in silico molecular docking studies for the inhibition of cyclooxygenase-2 (PDB ID: 1CX2) and voltage-gated sodium channels (PDB ID: 4F4L) comparable with the standard drugs. Thus, they were believed to be good inhibitors of cyclooxygenase-2 (PDB ID: 1CX2) and voltage-gated sodium channels (PDB ID: 4F4L).     

Nanostructural organization and anion effects on the temperature dependence of the optical Kerr effect spectra of ionic liquids

The intermolecular spectra of three imidazolium ionic liquids were studied as a function of temperature by the use of optical heterodyne-detected Raman-induced Kerr effect spectroscopy. The ionic liquids comprise the 1,3-pentylmethylimidazolium cation ([C(5)mim]+), and the anions, bromide (Br-), hexafluorophosphate (PF(6)-), and bis(trifluoromethanesulfonyl)imide (NTf(2)-). Whereas the optical Kerr effect (OKE) spectrum of [C(5)mim][NTf(2)] is temperature-dependent, the OKE spectra of [C(5)mim]Br and [C(5)mim][PF6] are temperature-independent. These results are surprising in light of the fact that the bulk densities of these room temperature ionic liquids (RTILs) are temperature-dependent. The temperature independence of the OKE spectra and the temperature dependence of the bulk density in [C(5)mim]Br and [C(5)mim][PF(6)] suggest that there are inhomogeneities in the densities of these liquids. The existence of density inhomogeneities is consistent with recent molecular dynamics simulations that show RTILs to be nanostructurally organized with nonpolar regions arising from clustering of the alkyl chains and ionic networks arising from charge ordering of the anions and imidazolium rings of the cations. Differences in the temperature dependences of the OKE spectra are rationalized on the basis of the degree of charge ordering in the polar regions of the RTILs.     

Alkylation of catechol with methanol to guaiacol over sulphate-modified zirconia solid acid catalysts

A series of sulphate-promoted ZrO₂ solid acid catalysts with different contents of SO₄ ²⁻ were calcined at 450°C in air for 4 h and tested for the liquid-phase alkylation of catechol to guaiacol in a fixed-bed down-flow reactor. The 5 wt.% SO₄ ²⁻ on ZrO₂ showed the best conversion (82%) and selectivity for guaiacol (84%) at 200°C and 1 bar pressure. A smooth correlation was observed between the catalytical activity and surface acidity of sulphated zirconia. Based on our results, a surface mechanism is proposed.     

Novel feature extraction technique for fuzzy relational clustering of a flexible dopamine reuptake inhibitor

This paper describes a novel clustering methodology for classifying over 700 conformations of a flexible analogue of GBR 12909, a dopamine reuptake inhibitor that has completed phase I clinical trials as a treatment for cocaine abuse. The major aspect of the clustering methodology includes an efficient data-conditioning scheme where a systematic feature extraction procedure based on the structural properties of the molecule was used to reduce the associated feature space. This allowed region-specific clustering that focused on individual pharmacophore elements of the molecule. For clustering of the reduced feature set, the fuzzy clustering partitional method was utilized. Due to the relational nature of the feature data, fuzzy relational clustering was employed, and it successfully detected natural groups defined by rotational minima around N(sp(3))-C(sp(3)), O(sp(3))-C(sp(3)), and C(sp(3))-C(sp(2)) bonds. The proposed clustering methodology also employed several cluster validity measures, which corroborated the partitions produced by the clustering technique and agreed with the results of hierarchical clustering using the XCluster program. Representative structures which exhibited a reasonable spread of energies and showed good spatial coverage of the conformational space were identified for use as putative bioactive conformations in a future Comparative Molecular Field Analysis of GBR 12909 analogues. The clustering methodology developed here is capable of handling other computational chemistry problems, and the feature extraction technique can be easily generalized to other molecules.     

Optical Modulation of Azobenzene‐Modified Peptide for Gold Surface Binding

The ability to precisely and remotely modulate reversible binding interactions between biomolecules and abiotic surfaces is appealing for many applications. To achieve this level of control, an azobenzene‐based optical switch is added to nanoparticle‐binding peptides in order to switch peptide conformation and attenuate binding affinity to gold surfaces via binding and dissociation of peptides.     

Some Novel Dinuclear phenylboronates of biologically potent β‐enaminoesters: Synthesis,Spectroscopic characterization,antimicrobial activity and their antiandrogenic effect

Organoboron derivatives of biologically potent β‐enamino esters of the type [Where R = CH₃(1a), C₂H₅ (1b), C₃H₇(1c) and C (CH₃)₃ (1d)] have been prepared by the reactions of β‐enamino esters and Phenyl boronic acid [PhB (OH)₂] in 1:2 molar ratio in refluxing tetrahydrofuran (THF). All these derivatives have been characterized by physico‐chemical properties, elemental analyses and molecular weight measurements. The structures of these compounds have been proposed on the basis of IR, ¹H, ¹³C, ¹¹B NMR spectral data and GC‐mass spectrometry. Phenyl boronic acid, β‐enamino esters and their respective phenylboronates derivatives have been screened for the antibmicrobial activities against pathogenic bacteria (B. subtilis and E. coli) and fungi (A. niger and P. peniculosum) to access their growth inhibiting potential. In addition to this, antiandrogenic effect of Ligand, L^aH₂ and its boron derivative (1a) has also been tested in male albino rats.