Effect of solvents on photophysical properties and quenching of 2-{[3-(1H-benzimidazole-2-yl) phenyl] carbonoimidoyl}phenol.

The effect of solvents of varying polarity on the absorption and fluorescence emission of the Schiff base, 2-{[3-(1H-benzimidazole-2-yl) phenyl]carbonoimidoyl}phenol, was studied using Lippert-Mataga bulk polarity function, Reichardt's microscopic solvent polarity parameter and Kamlet's multiple linear regression approach. The spectral properties follow Reichardt's microscopic solvent polarity parameter better than Lippert-Mataga bulk polarity parameter, indicating the presence of both general solute-solvent interactions and specific interactions. Catalan's multiple linear regression approach indicates the major role of solvent polarizability/dipolarity influence compared with solvent acidity or basicity. The solvatochromic effect was utilized to calculate the dipole moments of ground and excited states of the Schiff base using different methods. Bathochromic shift in the emission spectrum and the increase in dipole moment in the excited state signifies the intramolecular charge transfer character in the emitting singlet state. Fluorescence quenching by aniline was also studied in 1,4-dioxane and n-butanol, and the results were analyzed using sphere of action static quenching and finite sink approximation models.

Activation of -N=CH- bond in a Schiff base by divalent nickel monitored by NMR evidence.

The Schiff base, 2-salicylidene-4-aminophenyl benzimidazole in ethanol undergoes activation of -N=CH- bond by Ni(2+) in the presence of ammonia or primary alkyl amine to produce nickel complexes of the formula Ni{o-C(6)H(4)(O)CH NR}(2) . n H(2)O [R = H, Me; n = 0; R = Et, n = 0.5] and 4-aminophenyl benzimidazole. The products have been identified by elemental analysis, magnetic susceptibility measurements and IR, ESR, mass and extensive NMR spectral studies. The possible mechanism for the activation of -N=CH- bond has also been proposed.

CD36 modulates proinflammatory cytokine responses to Plasmodium falciparum glycosylphosphatidylinositols and merozoites by dendritic cells.

Studies have shown that glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum activate macrophages mainly through Toll-like receptor 2 (TLR2)-mediated signalling and to certain extent through TLR4-mediated signalling to induce proinflammatory cytokine production. However, the ability of parasite GPIs to activate dendritic cells (DCs) has not been reported. Here, we show that parasite GPIs efficiently activate DCs through TLR2-mediated signalling mechanism and induce the production of TNF-α and IL-12. We also studied the role of scavenger receptor CD36 in P. falciparum GPI- and merozoite-induced cytokine responses by DCs. The results indicate that CD36 modulates the cytokine-inducing activity of the parasite GPIs by collaborating with TLR2 in DCs. Furthermore, our data reveal that CD36 modulates the activity of P. falciparum merozoites, likely by the contribution of phagocytosis-coupled CD36-mediated signalling to the signalling induced by merozoites. Altogether, these results contribute towards understanding of signalling mechanisms in malaria parasite-induced activation of the innate immune system.

Synthesis of rhodium(III) complexes with tris/tetrakis-benzimidazoles and benzothiazoles--quick identification of cyclometallation by nuclear magnetic resonance spectroscopy.

Reactions of rhodium(III) halides with multidentate N,S-heterocycles, (LH3) 1,3,5-tris(benzimidazolyl)benzene (L1H3; 1), 1,3,5-tris(N-methylbenzimidazolyl) benzene (L2H3; 2) and 1,3,5-tris(benzothiazolyl)benzene (L3H3; 3), in the molar ratio 1:1 in methanol-chloroform produced mononuclear cyclometallated products of the composition [RhX2(LH2)(H2O)] (X = Cl, Br, I; LH2 = L1H2, L2H2, L3H2). When the metal to ligand (1-3 or 1,2,4,5-tetrakis(benzothiazolyl)benzene [L4H2; 4]) molar ratio was 2:1, the reactions yielded binuclear complexes of the compositions [Rh2Cl5(LH2)(H2O)3] (LH2 = L1H2, L2H2, L3H2) and [Rh2X4(L4)(H2O)2] (X = Cl, Br, I). Elemental analysis, IR and 1H nuclear magnetic resonance (NMR) chemical shifts supported the binuclear nature of the complexes. Cyclometallation was detected by conventional 13C NMR spectra that showed a doublet around approximately 190 ppm. Cyclometallation was also detected by gradient-enhanced heteronuclear multiple bond correlation (g-HMBC) experiment that showed cross-peaks between the cyclometallated carbon and the central benzene ring protons of 1-3. Cyclometallation was substantiated by two-dimensional 1H-1H correlated experiments (gradient-correlation spectroscopy and rotating frame Overhauser effect spectroscopy) and 1H-13C single bond correlated two-dimensional NMR experiments (gradient-enhanced heteronuclear single quantum coherence). The 1H-15N g-HMBC experiment suggested the coordination of the heterocycles to the metal ion via tertiary nitrogen.

Synthesis and NMR spectral assignments of novel nitrogen and sulfur heterocyclic compounds.

Synthesis and NMR spectral studies of multidentate N and S heterocycles, 1,3,5-tris(N-methylbenzimidazolyl)benzene, 1,3,5-tris(benzimidazolyl)benzene,1,3,5-tris(benzothiazolyl) benzene, 2,2'-bipyridine 3,3'-bis(benzothiazolyl)benzene and 1,2,4,5-tetrakis(benzothiazolyl) benzene have been carried out. 2D (1)H-(1)H PFG-COSY as well as (1)H-(13)C single and multiple bond correlated (2D GRASP-HSQC and GRASP-HMBC) experiments have been employed to characterize the compounds. 1D NOE experiments have been useful in understanding the structure of 1,3,5-tris(N-methylenzimidazolyl)benzene.

Sensitization of multidrug resistant (MDR) cancer cells to vinblastine by novel acridones: correlation between anti-calmodulin activity and anti-MDR activity.

Multidrug resistance (MDR) of cancer cells remains to be an important cause of chemotherapy failure. Search for the new MDR reversal agents is still an unceasing challenge for the scientists. In an attempt to find clinically useful modulators of MDR, a series of 19 N(10)-substituted-2-bromoacridones has been synthesized. Parent compound 1, prepared by the Ullmann condensation of o-chlorobenzoic acid and p-bromoaniline, undergoes N-alkylation in the presence of a phase transfer catalyst. N-(omega-Chloroalkyl) analogues were subjected to iodide catalyzed nucleophilic substitution reaction with various secondary amines to get the products 3-10 and 12-19, which increased the uptake of vinblastine (VLB) in MDR KBCh(R)-8-5 cells to a greater extent (1.25 to 1.9-fold) than did a similar concentration of the standard modulator, verapamil (VRP). Results of the efflux experiment showed that each modulator significantly inhibited the efflux of VLB, suggesting that they may be competitors for P-gp. All the compounds effectively compete with [(3)H] azidopine for binding to P-gp, pointed out this transport membrane protein as their likely site of action. Compounds at IC(10) were evaluated for their efficacy to modulate the cytotoxicity of VLB in KBCh(R)-8-5 cells and found that the modulators enhanced the cytotoxicity of VLB by 3.8 to 34-fold. The study on the structure-activity relationship revealed that substitution of hydrogen atom at position C-2 in acridone nucleus by a bromine atom increased the cytotoxic and anti-MDR activities. The ability of acridones to inhibit calmodulin-dependent cyclic AMP phosphodiesterase has been determined and the results have shown a strong positive correlation between anti-calmodulin activity and cytotoxicity in KBCh(R)-8-5 cells or anti-MDR activity.

Stability indicating RP-LC determination of sildenafil citrate (Viagra) in pure form and in pharmaceutical samples.

A simple, precise, sensitive and stability-indicating reverse-phase high performance liquid chromatographic (RP-HPLC) method has been developed for the quantitation of sildenafil citrate (SC) in pure form and its pharmaceutical formulations. Method employs water and acetonitrile (48:52 v/v) as mobile phase with flow rate of 1 ml min(-1), LiChrospher C18-5 microm (25 x 0.46 cm) column and UV detection set at 245 nm. The internal standard method using piroxicam (PX) as the internal standard is used. The linear dynamic range of SC was found to be 0.05-7.5 microg ml(-1). The proposed method is successfully employed for the determination of SC in the tablets. The excipients present in the formulations do not interfere with the assay procedure. Analytical parameters were calculated and full statistical evaluation is included.

Extractive spectrophotometric methods for the assay of sildenafil citrate (Viagra) in pure form and in pharmaceutical formulations.

Two simple and sensitive extractive spectrophotometric methods for the determination of sildenafil citrate (SC) are proposed. The methods are based on the formation of ion-association complexes of sildenafil citrate with bromocresol green (BCG, method A) and with chromoxane cyanine R (CCR, method B) in aqueous acidic buffer. The complex species, extractable to chloroform phase, were quantitatively measured at 415 and 460 nm for methods A and B, respectively. Beer's law was obeyed in the SC concentration range 1.25-25 mug ml(-1) with a limit of detection 0.16 mug ml(-1) and 1.5-60 mug ml(-1) with a limit of detection 0.18 mug ml(-1), respectively, for methods A and B. The methods have been successfully applied to the analysis of bulk drug and its tablets. No interference was observed from common pharmaceutical adjuvants.

Spectrophotometric methods for the determination of certain catecholamine derivatives in pharmaceutical preparations.

Two simple, rapid and sensitive spectrophotometric methods for the determination of catecholamine derivatives (pyrocatechol, dopamine, levodopa and methyldopa) are developed. The first method involves the oxidation of o-dihydroxybenzene derivatives by N-bromosuccinimide followed by oxidative coupling with isoniazid leading to the formation of a red-coloured products of maximum absorbance (lambda(max)=480-490 nm). The second method is based on the formation of green to blue complex (lambda(max)=635-660 nm) between o- dihydroxybenzene derivatives and sodium nitroprusside in the presence of hydroxylamine hydrochloride. All measurements of the two procedures are carried out in an alkaline medium at room temperature. The two methods are successfully applied for the determination of dopamine hydrochloride, levodopa and methyldopa in injections and tablets of pharmaceutical preparation. The common excipients used as additives in pharmaceuticals do not interfere in the proposed methods. The reliability of these methods are established by parallel determination with the reported and official methods.

Sterol hydroperoxide metabolism by Salmonella typhimurium.

In order to rationalize multiphasic dose-response data evincing mutagenicity towards Salmonella typhimurium TA1537 for sterol hydroperoxides 3 beta-hydroxy-5 alpha-cholest-6-ene-5-hydroperoxide and 3 beta-hydroxycholest-5-ene-7 alpha-hydroperoxide their metabolism by the bacterial test strain was investigated. The 5 alpha-hydroperoxide was isomerized to the 7 alpha-hydroperoxide and reduced to 5 alpha-cholest-6-ene-3 beta,5-diol; the 7 alpha-hydroperoxide was reduced to cholest-5-ene-3 beta,7 alpha-diol and transformed to 3 beta-hydroxycholest-5-en-7-one. The 3 beta,5 alpha-diol and 3 beta,7 alpha-diol were not interconverted nor was either transformed to the 7-ketone.

Titrimetric determination of vitamin B6 using chloramine-T, bromamine-T, and bromamine-B.

Simple titrimetric methods have been developed for determination of the vitamin pyridoxine (PRX) in solution, using aromatic N-haloamines, chloramine-T, bromamine-T, and bromamine-B. The method is based on oxidation of PRX by the N-haloamines; the oxidation involves a 2-electron change. The reaction products, pyridoxal and sulfonamides, were identified. The effects of variables, such as pH of the medium and the presence of foreign ions, and pyridoxal, pyridoxalamine, glycerol, and alcohol, on the rate of oxidation were studied. The methods are useful for determining PRX in pharmaceutical formulations and for assaying its cadmium complex. Statistical evaluation showed that analytical results are accurate to within 1%.

Application of Azure C for the extractive spectrophotometric determination of microgram amounts of penicillin.

A simple, accurate, and rapid method for the quantitative determination of penicillin is proposed. The method is based on the formation of a blue penicillin-Azure-C ion-pair that can be extracted into chloroform in phosphate-citric acid buffer. The molar absorptivities for sodium penicillin G and potassium penicillin V at 635 nm were 5.46 X 10(3) and 2.19 X 10(4) l/mol/cm, respectively. Beer's law was valid over the concentration range of 4-80 micrograms/ml for sodium penicillin G and 3-55 micrograms/ml for potassium penicillin v. Maximum absorbance was obtained almost instantaneously and was stable for several days. The method was successfully applied to pharmaceutical preparations.

On reaction of sterol hydroperoxides with superoxide.

Reduction of sterol hydroperoxides 3 beta-hydroxy-5 alpha-cholest-6-ene-5-hydroperoxide and cholesterol 7 alpha-hydroperoxide by KO2 (or other strong base in air) solubilized by crown ether in dimethylsulfoxide gave only corresponding alcohols, but in the presence of cholesterol (or other sterols) gave 3 beta-hydroxycholest-5-en-7-one together with the corresponding alcohols. Both hydroperoxides likewise gave the corresponding alcohol and ketone products with KO2 in benzene and in oxidations by ceric ammonium nitrate in a biphasic system. The 7-ketone product is recognized as deriving from termination reactions of sterol peroxyl and/or oxyl radicals.

Inactivation of poliovirus by chloramine-T.

Since concern has recently been expressed about the presence of genotoxic substances due to chlorination of water and wastewater, chloramine-T (CAT) is proposed as an alternative disinfectant to chlorine. The viricidal properties of chlorine and CAT were compared. Kinetics of inactivation of poliovirus type 2 by chlorine and CAT in chlorine demand-free water were investigated by using a kinetic apparatus. Inactivation of the virus by chlorine and CAT occurred in two steps. The initial linear part of the inactivation curve followed a pseudo-first-order reaction with the virus. An obvious dose-response relationship was demonstrated with CAT. The rate of inactivation of the virus by CAT was faster in acid medium than in alkaline medium. Inactivation kinetic studies were performed at different temperatures, and the kinetic, Arrhenius, and thermodynamic parameters were evaluated. The rate of inactivation of poliovirus type 2 by chlorine was faster than that by CAT under identical conditions. A mechanism for the viral inactivation in acid conditions was proposed which led to a rate equation consistent with the experimental results. The results indicate that CAT may be an effective viricide against poliovirus type 2 in an acid medium.

Estimation of methionine and its metal complexes by oxidation with chloramine-T and dichloramine-T.

A simple method for the estimation of methionine (HMt) in aqueous solution has been developed, based on its oxidation with chloramine-T and dichloramine-T at room temperature. The direct titration, with visual or potentiometric end-point involves a two-electron change, corresponding to the formation of methionine sulphoxide. Most amino-acids do not interfere, but cysteine, glutathione and thiourea are oxidized under these conditions. A back-titration procedure in which methionine is oxidized in 0.1M sodium hydroxide by excess of chloramine-T with a four-electron change corresponding to the formation of methionine sulphone has also been developed. Methionine is oxidized to the respective nitrile, however, with excess of dichloramine-T. The methods have also been employed in estimating methionine in two of its soluble complexes, [NiMt]ClO(4) and Na[AgMt(2)].

Estimation of glutathione with chloramine-T and dichloramine-T.

A simple but accurate method for the estimation of glutathione in aqueous solution has been developed, based on its oxidation with chloramine-T and dichloramine-T at room temperature. The direct titration with a visual or potentiometric end-point involves a one-electron change, corresponding to the oxidation of the thiol group to disulphide. Most amino-acids do not interfere, but cysteine, methionine and thiourea are oxidized under these conditions. A back-titration procedure in which glutathione is oxidized by excess of chloramine-T with a 10-electron change at pH 5 has also been developed.