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Kinetic studies of the oxidation of d-mannose, d-glucose, d-fructose, l-arabinose and d-ribose by bromamine-T (sodium N-bromo-p-toluenesulphonamide or BAT) and bromamine-B (sodium N-bromobenzenesulphonamide or BAB) in alkaline medium were investigated at 30°C. The rate of the reaction was first order both with respect to the oxidant and the sugar and second order with respect to [HO−]. The addition of the reaction product, p-toluenesulphonamide (PTS) or benzenesulphonamide (BSA), and the variation of ionic strength of the medium have no effect on the rate. The rate decreases with decrease in dielectric constant of the medium and values of dAB, the size of activated complex, were calculated. Proton inventory studies were made in H2O–D2O mixtures. The activation parameters of the reaction were computed from Arrhenius plots. HPLC and GLC-MS analysis of the products indicated that the sugars were oxidized to a mixture of aldonic acids consisting of arabinonic, ribonic, erythronic and glyceric acids. A general...

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.

The kinetics of oxidation of uronic acids (UAs), d-glucuronic acid and d-galacturonic acid, by sodium N-bromo-p-toluenesulfonamide or bromamine-T (BAT) and sodium N-bromobenzenesulfonamide or bromamine-B (BAB) in alkaline medium at 30°C have been investigated and the rate law, rate=k [OX] [UA] [HO−] where [OX]˭[BAT] or [BAB] was observed. The product p-toluenesulfonamide (PTS) or benzenesulfonamide (BSA) and ionic strength have no influence on the rate. The rate decreased when the dielectric constant (ϵ) of the medium was decreased. The rate increased in D2O medium. Proton inventory studies were made in D2O–H2O mixtures. Effect of temperature was studied and from the Arrhenius plots, activation parameters were computed. A mechanism involving the formation of enediol anion, which reacts with positive bromine of the bromamine in the rate-limiting step is suggested.

1,3-Dipolar cycloaddition reaction of nitrones to olefins is of synthetic interest. In the present work, isoxazolidines have been synthesized in high yield via intermolecular cycloaddition of N-arylnitrone with monosubstituted olefins and are employed for biological evaluation.

The synthesis of adducts of arylamines with adenosine are reported.

Dipeptides (DP) namely phenylalanyl-proline (Phe-Pro), isoleucyl-proline (Ile-Pro) and leucyl-proline (Leu-Pro) were synthesized by classical solution method and characterized The kinetics of oxidation of these DP by Mn(III) have been studied in the presence of sulphate ions in acidic medium at 26degreesC. The reaction was followed spectrophotometrically at lambda(max) = 500 nm. A first-order dependence of rate on both Mn(III)](0) and \textbackslashDP\textbackslash(0) was observed. The rate is independent of the concentration of reduction product, Mn(II), and hydrogen ions. The effects of varying dielectric constant of the medium and addition of anions such as sulphate, chloride and perchlorate were studied The activation parameters have been evaluated using Arrhenius and Eyring plots. The oxidation products were isolated and characterized A mechanism involving the reaction of DP with Mn(III) in the rate-limiting step is suggested. (C) 2002 Wiley Periodicals, Inc.

Propylphosphonic anhydride (T3P®)–DMSO-mediated one-pot three-component synthesis which provides 2-arylquinolines in a single step from benzyl alcohols, anilines, and ethyl vinyl ether by the modif...

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that regulates genes involved in cell growth, proliferation, and survival, and given its association with many types of cancers, it has recently emerged as a promising target for therapy. In this work, we present the synthesis of N-substituted azaspirane derivatives and their biological evaluation against hepatocellular carcinoma (HCC) cells (IC50 = 7.3 μm), thereby identifying 2-(1-(4-(2-cyanophenyl)1-benzyl-1H-indol-3-yl)-5-(4-methoxy-phenyl)-1-oxa-3-azaspiro(5,5) undecane (CIMO) as a potent inhibitor of the JAK-STAT pathway with selectivity over normal LO2 cells (IC50 > 100 μm). The lead compound, CIMO, suppresses proliferation of HCC cells and achieves this effect by reducing both constitutive and inducible phosphorylation of JAK1, JAK2, and STAT3. Interestingly, CIMO displayed inhibition of Tyr-705 phosphorylation, which is required for nuclear translocation of STAT3, but it has no effect on Ser-727 phosphorylation. CIMO accumulates cancer cells in the sub-G1 phase and decreases STAT3 in the nucleus and thereby causes down-regulation of genes regulated via STAT3. Suppression of STAT3 phosphorylation by CIMO and knockdown of STAT3 mRNA using siRNA transfection displayed a similar effect on the viability of HCC cells. Furthermore, CIMO significantly decreased the tumor development in an orthotopic HCC mouse model through the modulation of phospho-STAT3, Ki-67, and cleaved caspase-3 in tumor tissues. Thus, CIMO represents a chemically novel and biologically in vitro and in vivo validated compound, which targets the JAK-STAT pathway as a potential cancer treatment.

A new, simple, and microwave-assisted, solution-phase T3P®-DMSO mediated method for the preparation of a novel class of estrogen receptor alpha (ERα) ligands based on the 2-phenylquinoline scaffold was developed. Furthermore, the novel ERα ligands were tested for their bioactivity against ERα-positive and ERα-negative cell lines. The ligand (entry 4), with amine and nitro group substitution at C4 position, displayed significant cytotoxicity against MCF-7 and HepG2 cells with an IC50 value of 6 and 11 μM, respectively. On the other hand, ERα-negative cells displayed resistance to quinolines induced cytotoxicity with an IC50 value >100 Mm and they does not induce cytotoxicity in normal breast epithelial cells. Molecular docking analyses suggest a consistent binding mode for these ERα ligands in the ligand binding domain of the human ERα and predict the ligands to occupy the hydrophobic cavity in a similar fashion as estradiol or GW2368.

Bismuth oxide was synthesized via simple, rapid and energy efficient solution combustion synthesis (SCS) by employing sucrose as a fuel. This SCS-Bi2O3 was characterized by analytical techniques such as PXRD, SEM, EDX, UV-Visible and BET surface area measurement. Using the prepared SCS-Bi2O3, several classes of heterocyclic compounds were synthesized in good yields via Suzuki-coupling reaction in aqueous medium. Interestingly, the recovered SCS-Bi2O3 could be reused three times without a significant loss of catalytic activity. Further, the synthesized compounds were tested for cytotoxic activity against a human hepatoma cancer cell line (HepG2). Among these, compound 3n effectively inhibited the proliferation of these cells with an IC50 value of 8.4 μM. Thus, this paper describes the preparation of highly effective Bi2O3, which can be used for synthesizing various classes of heterocycles, including those having anti-cancer property.

Dihydropyrimidinones of type (IV) or (VI) are prepared by the Biginelli reaction using alcohols, β-ketoesters or β-oxodithioesters in the presence of propylphosphonic anhydride (T3P®)/DMSO which is used to oxidize the alcohols into the corresponding aldehydes.

A new strategy was developed to synthesize 1,2-disubstituted 4-quinolones in good yield starting from 1,3-bisaryl-monothio-1,3-diketone substrates. The synthesized compounds were evaluated for antimalarial activity using Plasmodium falciparum strains. All compounds, except for two, showed good activity. Of these, seven compounds exhibited an excellent antimalarial activity (IC50,2 μM). More importantly, all seven compounds were equally effective in inhibiting the growth of both chloroquine-sensitive and chloroquine-resistant strains. The cytotoxicity assessment using carcinoma and non-carcinoma human cell lines revealed that almost all synthesized compounds were minimally cytotoxic (IC50,50 μM).

TNF is a pleotropic cytokine known to be involved in the progression of several pro-inflammatory disorders. Many therapeutic agents have been designed to counteract the effect of TNF in rheumatoid arthritis as well as a number of cancers. In the present study we have synthesized and evaluated the anti-cancer activity of novel biscoumarins in vitro and in vivo. Among new compounds, BIHC was found to be the most cytotoxic agent against the HepG2 cell line while exhibiting less toxicity toward normal hepatocytes. Furthermore, BIHC inhibited the proliferation of various hepatocellular carcinoma (HCC) cells in a dose- and time-dependent manner. Subsequently, using in silico target prediction, BIHC was predicted as a TNF blocker. Experimental validation was able to confirm this hypothesis, where BIHC could significantly inhibit the recombinant mouse TNF-α binding to its antibody with an IC50 of 16.5 μm. Furthermore, in silico docking suggested a binding mode of BIHC similar to a ligand known to disrupt the native, trimeric structure of TNF, and also validated with molecular dynamics simulations. Moreover, we have demonstrated the down-regulation of p65 phosphorylation and other NF-κB-regulated gene products upon BIHC treatment, and on the phenotypic level the compound shows inhibition of CXCL12-induced invasion of HepG2 cells. Also, we demonstrate that BIHC inhibits infiltration of macrophages to the peritoneal cavity and suppresses the activity of TNF-α in vivo in mice primed with thioglycollate broth and lipopolysaccharide. We comprehensively validated the TNF-α inhibitory efficacy of BIHC in an inflammatory bowel disease mice model.

A facile, convenient, and multicomponent coupling strategy for the synthesis of highly functionalized pyrroles is developed using graphite as a catalyst, but devoid of moisture-sensitive metal catalysts and corrosive acidic reagents. This method involves four-component coupling reactions of ethyl acetoacetate compound or diethyl acetylene dicarboxylate, amines, aromatic aldehydes, and nitromethane without an inert atmosphere. This approach provides easy access to highly substituted pyrroles in good yields via one-pot tandem reaction. The method is very simple, straightforward, and environmentally friendly compared to the existing methods. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]

Glycoside hydrolases catalyze the selective hydrolysis of glycosidic bonds in oligosaccharides, polysaccharides, and their conjugates. β-glucosidases occur in all domains of living organisms and constitute a major group among glycoside hydrolases. On the other hand, the benzoxazinoids occur in living systems and act as stable β-glucosides, such as 2-(2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one)-β-D-gluco-pyranose, which hydrolyse to an aglycone DIMBOA. Here, we synthesized the library of novel 1,3-benzoxazine scaffold based aglycones by using 2-aminobenzyl alcohols and aldehydes from one-pot reaction in a chloroacetic acid catalytic system via aerobic oxidative synthesis. Among the synthesized benzoxazines, 4-(7-chloro-2,4-dihydro-1H-benzo[d][1,3]oxazin-2-yl)phenol (compound 7) exhibit significant inhibition towards glucosidase compared to acarbose, with a IC50 value of 11.5 µM. Based upon results generated by in silico target prediction algorithms (Naive Bayesian classifier), these aglycones potentially target the additional sodium/glucose cotransporter 1 (where a log likelihood score of 2.70 was observed). Furthermore, the in vitro glucosidase activity was correlated with the in silico docking results, with a high docking score for the aglycones towards the substrate binding site of glycosidase. Evidently, the in vitro and in vivo experiments clearly suggest an anti-hyperglycemic effect via glucose uptake inhibition by 4-(7-chloro-2,4-dihydro-1H-benzo[d][1,3]oxazin-2-yl)phenol in the starved rat model. These synthetic aglycones could constitute a novel pharmacological approach for the treatment, or re-enforcement of existing treatments, of type 2 diabetes and associated secondary complications.

2,4-Disubstituted thiophene derivatives were synthesized and assessed for antiinflammatory and anti-cancer activities by targeting two important enzymes of the arachidonic acid metabolism. Both lipoxygenase and cyclooxygenase enzymes play vital role in chronic inflammation and carcinogenesis. Previous studies have proved that COX-2 and 5-LOX are highly activated in various types of cancers; hence inhibition of these clinically important enzymes constitutes the essential criterion for the suppression of tumor progression and metastasis. Among the tested derivatives, 2d and 2g compounds emerged as potent inhibitors of lipoxygenase and cyclooxygenase enzymes. The potent inhibitor of cyclooxygenase was further tested for in vitro cytotoxicity on cervical cancer (HeLa) cells and in vivo tumor model studies using EAT bearing mice where 2-(3,4,5- trimethoxyphenyl)-4-(N-methylindol-3-yl) thiophene (2g) showed eloquent activity. Further, in silico modeling results confirmed the active catalytic ligand binding pockets, which is evident from higher atomic contact energy values of 2d and 2g than compared to standard drug. Thus, 2g may find better application in management of inflammation and in proapoptotic therapeutic engineering.

Thirteen 2-oxazine-based small molecules were synthesized targeting 5-lipoxygenase (LOX), and acetylcholinesterase (AChE). The test revealed that the newly synthesized compounds had potent inhibition towards both 5-LOX and AChE in lower micro molar concentration. Among the tested compounds, the most active compound, 2-[(2-acetyl-6,6-dimethyl-4-phenyl-5,6-dihydro-2H-1,2-oxazin-3-yl)methyl]-1H-isoindole-1,3(2H)-dione (2a) showed inhibitory activity towards 5-LOX and AChE with an IC50 values of 1.88, and 2.5 μM, respectively. Further, the in silico molecular docking studies revealed that the compound 2a bound to the catalytic domain of AChE strongly with a highest CDOCKER score of −1.18 kcal/mol when compared to other compounds of the same series. Additionally, 2a showed a good lipophilicity (log P = 2.66), suggesting a potential ability to penetrate the blood–brain-barrier. These initial pharmacological data revealed that the compound 2a could serve as a drug-seed in developing anti-Alzheimer’s agents.

The reaction of 2,4-dichloroacetophenone leads also to significant amounts of methylthio substituted products (VI).

The present work reveals the synthesis and antiproliferative effect of a series of 2, 3 disubstituted 4-thiazolidinone analogues on human leukemic cells. The chemical structures of newly synthesized compounds were confirmed by IR, H-1 NMR, C-13 NMR and mass spectral analysis. Compound methyl 3-methoxy-4-(4-oxo-3-(5-(piperazin-1-yl)pyridin-2-yl)thiazolidin-2-yl)be nzoate (5) displayed potent activity (IC50 9.71, 15.24 and 19.29 mu M) against Nalm6, K562, Jurkat cells. Cell cycle analysis and mitochondrial membrane potential further confirmed that compound 5 is cytotoxic and able to induce cell death. (C) 2014 Elsevier Masson SAS. All rights reserved.

Secretory phospholipases A2 (sPLA2s) are present in snake venoms, serum, and biological fluids of patients with various inflammatory, autoimmune and allergic disorders. Lipid mediators in the inflammatory processes have potential value for controlling phospholipid metabolism through sPLA2 inhibition. Thus, it demands the need for screening of potential leads for sPLA2 inhibition. To date, sPLA2 activity has been assayed using expensive radioactive or chromogenic substrates, thereby limiting a large number of assays. In this study, a simple and sensitive NanoDrop assay was developed using non-fluorogenic and non-chromogenic phospholipid substrate 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 8-anilino-1-naphthalenesulfonic acid (ANS) as interfacial hydrophobic probe. The modified assay required a 10ng concentration of sPLA2. ANS, as a strong anion, binds predominantly to cationic group of choline head of DMPC through ion pair formation, imparting hydrophobicity and lipophilicity and resulting in an increase in fluorescence. Triton X-100 imparts correct geometrical space during sPLA2 catalyzing DMPC, releasing lysophospholipid and acidic myristoyl acid, which in turn alters the hydrophobic environment prevailing around ANS-DMPC, which leads to weakening of the electrostatic ion pair interaction between DMPC and ANS ensuing decrease in fluorescence. These characteristic fluorescence changes between DMPC and ANS in response to sPLA2 catalysis are well documented and validated in this study.

The reported strategy allows a novel entry to 2,4,5-trisubstituted thiazoles avoiding the limitations of Hantzsch type condensations.

The classical antivenom therapy has appreciably reduced snakebite mortality rate and thus is the only savior drug available. Unfortunately, it considerably fails to shield the viper bite complications like hemorrhage, local tissue degradation and necrosis responsible for severe morbidity. Moreover, the therapy is also tagged with limitations including anaphylaxis, serum sickness and poor availability. Over the last decade, snake venom metalloproteases (SVMPs) are reported to be the primary component responsible for hemorrhage and tissue degradation at bitten site. Thus, antivenom inability to offset viper venom-induced local toxicity has been a basis for an insistent search for SVMP inhibitors. Here we report the inhibitory effect of compound 5d, an apigenin based molecule against SVMPs both in silico and in vivo. Several apigenin analogues are synthesized using multicomponent Ugi reactions. Among them, compound 5d effectively abrogated Echis carinatus (EC) venom-induced local hemorrhage, tissue necrosis and myotoxicity in a dose dependant fashion. The histopathological study further conferred effective inhibition of basement membrane degradation, and accumulation of inflammatory leucocytes at the site of EC venom inoculation. The compound also protected EC venom-induced fibrin and fibrinogen degradation. The molecular docking of compound 5d and bothropasin demonstrated the direct interaction of hydroxyl group of compound with Glu146 present in hydrophobic pocket of active site and does not chelate Zn2+. Hence, it is concluded that compound 5d could be a potent agent in viper bite management.

The kinetics of oxidation of dipeptides (DP), namely phenylalanyl-glycine (Phe-Gly), isoleucyl-glycine (Ile-Gly) and leucyl-glycine (Leu-Gly), by Mn(III) have been studied in the presence of sulfate ions in acidic solution at 26 °C. The reaction was followed spectrophotometrically at λmax = 500 nm. A first-order dependence of the rate on both [Mn(III)] and [DP] was observed. The rate is independent of the concentration of reduction product, Mn(II) and hydrogen ions. The effects of varying the dielectric constant of the medium and addition of anions such as sulfate, chloride and perchlorate were studied. The activation parameters have been evaluated using Arrhenius and Eyring plots. The oxidation products were isolated and characterized. A mechanism involving the reaction of DP with Mn(III) in the rate limiting step is suggested.

The kinetics of the Ru(III) catalysed oxidation of six derivatives of phenethyl alcohol (X-C6H4-CH2CH2OH where X═H, Cl, Br, CH3, OCH3 or NO2) by manganese(III) sulfate, in sulfuric acid solution at 30°C, were followed spectrophotometrically at λmax =500 nm. The rate shows a first-order dependence on [Mn(III)] and Michaelis-Menten kinetics was observed with the substrate. The rate was of fractional-order in [Ru(III)]. Hammett acidity function (─H0) has been invoked to explain the retardation of the rate by acid. Bunnett plots indicated the absence of water molecule participation in the rate-limiting step. Variation of the ionic strength and the dielectric constant and the addition of the reaction product Mn(II) and anions such as C1−, SO2+ 4, and F− have no effect on the rate. The solvent isotope effect k(H2O)/k(D2O) =1.38 was observed. Proton inventory studies were made in H2O-D2O mixtures. A linear free energy relationship was observed when the results were analyzed by Hammett and Okamoto-Brown equations...

α, N-diarylnitrones were synthesized by the reduction of a mixture of nitro-and benzaldehyde derivatives with zinc dust using histidine as a catalyst.

The fragments of elastin sequences, glycyl-alanyl-proline (GAP), glycyl-valyl-proline (GVP), glycyl-isoleucyl-proline (GIP) and glycyl-leucyl-proline (GLP) were synthesized by a classical solution phase method and characterized. The kinetics of oxidation of these tripeptides (TP) by Mn(III) has been studied in the presence of sulfate ions in acidic solution at 25°C. The reaction was followed spectrophotometrically at λmax = 500 nm. A first-order dependence of rate on both [Mn(III)] and [TP] was observed. The rate is independent of the concentration of the reduction product, Mn(II), and hydrogen ions. The effects of varying the dielectric constant of the medium and addition of anions such as sulfate, chloride or perchlorate were studied. Activation parameters have been evaluated using Arrhenius and Eyring plots. The oxidation products were isolated and characterized. A mechanism involving the reaction of TP with Mn(III) in the rate-limiting step is suggested. The effect of hydrophobicity of the amino acids...

The kinetics and mechanism of oxidation of D-glucuronic acid and D-galacturonic acid by manganese(III) sulfate, in aqueous sulfuric acid solution at 30°C, was followed spectrophotometrically at λmax=500 nm. A first-order dependence of the rate each on [Mn(III)] and [uronic acid] was observed. The rate is independent of the concentration of hydrogen ions and the reaction product, Mn(II). Effects of varying the dielectric constant of the medium and the addition of anions such as Cl−, F−, SO2 4 and ClO4 − have been investigated. Activation parameters have been evaluated using Arrhenius and Eyring plots. A mechanism involving the formation of an enediol from uronic acid which reacts with Mn(III) in the rate-limiting step is suggested.

The isolation of stable carbenes of the Arduengo (1a) and Wanzlick (2a) type has prompted us to look for stable nitrenium ions of the related structural type 1,3-dimethyl benzotriazolium trifluoromethane sulfonate (3+ ). The title compound was isolated and structure was characterized by X-ray methods.

A rapid, simple, sensitive and selective spectrophotometric determination of nitrite using new diazotizing and coupling reagents is described. The method is based on a diazotization-coupling reaction between dapsone and iminodibenzyl in a hydrochloric acid medium. The molar absorptivity and Sandell's sensitivity were found to be 7.5 x 10(4) l mol(-1) cm(-1) and 0.000613 microg ml(-1), respectively. The interference effects of various cations and anions were also studied and reported. This method has been found to be applicable for the determination of nitrite in various water samples.

The oxidation of para-substituted phenethyl alcohols (PEA, 2) by N-metallo-N-haloarylsulphonamides (1) in the presence of dilate HCl to the corresponding phenacetaldehydes (4) is first order with respect to oxidant (1) and H+] and a fractional order each in PEA] and Cl-]. Addition of the reaction product (3), ionic strength variations and variation of dielectric constant of the medium had no effect on the rate. The oxidation of PhCH2CD2OH (2) exhibited a substantial primary kinetic isotope effect (k(H)/k(D) = 5.83). The rates correlate satisfactorily with the Hammett free energy relationship. The activation parameters AH(#), AS(#), AG(#) and logA were calculated for the reaction. The proposed mechanism is consistent with the observed results. Copyright (C) 2001 John Wiley & Sons, Ltd.

The analogues of elastin sequences, glycyl-glycyl-alanyl-proline (GGAP), glycyl-glycyl-phenylalanyl-proline (GGFP), and glycyl-glycyl-isoleucyl-proline (GGIP) were synthesized by classical solution phase method and characterized. The kinetics of oxidation of these tetrapeptides (TETP) by Mn(III) has been studied in the presence of sulphate ions in acidic solution at 25°C. The reaction was followed spectrophotometrically at λmax = 500 nm. A first-order dependence of rate on both [Mn(III)] and [TETP] was observed. The rate is independent of the concentration of the reduction product, Mn(II), and hydrogen ions. The effects of varying the dielectric constant of the medium and addition of anions such as sulphate, chloride, or perchlorate were studied. Activation parameters have been evaluated using Arrhenius and Erying plots. The oxidation products were isolated and characterized. A mechanism involving the reaction of TETP with Mn(III) in the rate-limiting step is suggested. An apparent correlation was noted between the rate of oxidation and the hydrophobicity of these sequences, where increased hydrophobicity results in increased rate of oxidation. © 2001 John Wiley & Sons, Inc. Int J Chem Kinet 34: 39–48, 2002

The repeating sequence of elastin, valylprolylglycylvalylglycine (VPGVG), its permutation pentamer glycylvalylglycylvalylproline (GVGVP), and its more hydrophobic pentamer glycylphenylalanylglycylvalylproline (GFGVP) were synthesized by classical solution-phase methods and characterized. The kinetics of the oxidation of these pentapeptides (PP) by Mn(III) was studied in the presence of sulphate ions in acidic medium at 25 degreesC. The reaction was followed spectrophotometrically at lambda (max) = 500 nm. A first-order dependence of rate on both Mn(III)] and PP] was observed. The rate is independent of concentration of the reduction product, Mn(H) and hydrogen ions. Effects of varying dielectric constant of the medium and addition of anions such as sulphate, chloride and perchlorate were studied. Activation parameters were evaluated using Arrhenius and Eyring plots. The oxidation products were isolated and characterized. A mechanism involving the reaction of PP with Mn(HI) in the rate-limiting step is suggested. An apparent correlation was noted between the rate of oxidation and the hydrophobicity of these sequences where increased hydrophobicity results in an increased rate of oxidation. Further, it was observed that the pentamers with Pro as C-terminus are more susceptible to oxidation than the pentamer with Gly as C-terminus. Copyright (C) 2001 John Wiley & Sons, Ltd.

Kinetics of oxidation of α -amino acids, glycine, valine, alanine, and phenylalanine, by sodium N-chloro-p-toluenesulfonamide or chloramine-T (CAT) has been investigated in HClO4 medium at 30°C. The rate shows first-order dependence on both CAT and amino acid concentrations and an inverse first-order on [H+]. The variation of ionic strength and the addition of p-toluenesulfonamide and Cl− ion had no effect on the reaction rate. Decrease of dielectric constant of the medium by increasing the MeOH content decreased the rate. Rate studies in D2O medium showed the inverse solvent-isotope effect of kD2O/kH2O=0.50. Proton-inventory studies were carried out using H2O–D2O mixtures. The activation parameters have been computed. The proposed mechanism and the derived rate law are consistent with the observed kinetic data. An isokinetic relationship is observed with β=323 K, indicating enthalpy as a controlling factor. The rate of oxidation increases in the following order: Gly < Val < Phe < Ala. © 2001 John Wiley & Sons, Inc. Int J Chem Kinet 34: 49–55, 2002

Viper bites cause high morbidity and mortality worldwide and regarded as a neglected tropical disease affecting a large healthy population. Classical antivenom therapy has appreciably reduced the snakebite mortality rate; it apparently fails to tackle viper venom-induced local manifestations that persist even after the administration of antivenom. Recently, viper venom-induced oxidative stress and vital organ damage is deemed as yet another reason for concern; these are considered as postmedicated complications of viper bite. Thus, treating viper bite has become a challenge demanding new treatment strategies, auxiliary to antivenin therapy. In the last decade, several studies have reported the use of plant products and clinically approved drugs to neutralize venom-induced pharmacology. However, very few attempts were undertaken to study oxidative stress and vital organ damage. Based on this background, the present study evaluated the protective efficacy of melatonin in Echis carinatus (EC) venom-induced tissue necrosis, oxidative stress, and organ toxicity. The results demonstrated that melatonin efficiently alleviated EC venom-induced hemorrhage and myonecrosis. It also mitigated the altered levels of inflammatory mediators and oxidative stress markers of blood components in liver and kidney homogenates, and documented renal and hepatoprotective action of melatonin. The histopathology of skin, muscle, liver, and kidney tissues further substantiated the overall protection offered by melatonin against viper bite toxicities. Besides the inability of antivenoms to block local effects and the fact that melatonin is already a widely used drug promulgating a multitude of therapeutic functionalities, its use in viper bite management is of high interest and should be seriously considered.

In the title compound, C23H20F3N3O3S2, the benzoimidazole unit makes dihedral angles of 5.02 (1) and 76.42 (1)°, respectively, with the pyridine and methylbenzene rings; the dihedral angle between the pyridine and methylbenzene rings is 72.19 (1)°. In the crystal, molecules are connected by weak C—H...F, C—H...O and C—H...N hydrogen bonds. Weak C—H...π interactions and π–π stacking [centroid–centroid distance = 3.6485 (14) Å] are also observed. The overall packing shows a three-dimensional architecture. The crystal structure contains a void of 51 Å3, but no solvent molecule (hexane or ethyl acetate) is located within it.

The structures of the title compounds, tris(2-hydroxy-3-t-butyl-5-methylbenzene)-methane)C34H46O3.3H2O, 3) and N-benzyl-N-phenylbenzamide (C20H17NO, 6), have been investigated by X-ray crystallography. Compound 3 crystallizes in the trigonal space group $$P\bar 3 $$ with cell parameters a = 14.090(5) A, b = 14.090(5)A, c = 10.485(5)A, Z = 2. Compound 6 crystallizes in the monoclinic space group C2/c with cell parameters a = 24.533(4)A, b = 9.176(4)A, c = 16.711(5)A, β = 125.88(2)°, Z = 8. Compound 3 has both intra-and intermolecular hydrogen bonds. It also exhibits a helical columnar arrangement of the molecules and goes into mesophase before melting into an isotropic liquid.

A simple, fast, efficient and environmentally friendly synthesis of benzimidazole and its 2-alkyl, aryl and heteroaryl substituted derivatives was developed using zeolite HY. Two component cyclolcondensation of 1,2-phenylenediamine (o-phenylenediamine) and commercially available carboxylic acids catalyzed by zeolite HY without any solvent under microwave irradiation leads to 1H-benzimidazole and 2-substituted derivatives in high yields and purity. The similar reaction was not applicable to the preparation of benzimidazole and its 2-alkyl, aryl and heteroaryl substituted derivatives. All the synthesized compounds were characterized by 1H-NMR, IR, Mass and CHNS analysis.

Kinetics and mechanism of oxidation of L-serine by manganese(III) ions have been studied in aqueous sulfuric acid medium at 323 K. Manganese(III) sulfate was prepared by an electrolytic oxidation of manganous sulfate in aqueous sulfuric acid. The dependencies of the reaction rate are: an unusual one and a half-order on Mn(III)], first-order on ser], an inverse first-order on H+], and an inverse fractional-order on Mn(II)]. Effects of complexing agents and varying solvent composition were studied. Solvent isotope studies in D2O medium were made. The dependence of the reaction rate on temperature was studied and activation parameters were computed from Arrhenius-Eyring plots. A mechanism consistent with the observed kinetic data has been proposed and discussed. (C) 1999 John Wiley & Sons, Inc.

I. 3,5-diphenyl triazole, C14H11N3, Mr = 221.26, monoclinic, Cc, a = 26.982(6) A, b = 5.6806(14) A, c = 7.439(2) A, β = 105.54(2)°, V = 1098.6(5) A3, Z = 4, Dm = 1.312gm·cm−3, Dc = 1.338gm·cm−3, μ = 0.083cm−1, F000 = 464, (MoKα) = 0.71069 A, final R1 and wR2 are 0.0335 and 0.0985 respectively. Hydrogen bonds of the type CH···N are observed in the crystal structure of the compound. The molecules are packed in layers when viewed along b and c, whereas down a it shows a herringbone type of arrangement. II. 4-phenylimidazole, C9H8N2, Mr = 144.18, monoclinic, Pa, a = 7.0291(13) A, b = 12.5142(8) A, c = 9.4476(12) A, β = 100.639(12)°, V = 816.76(18) A3, Z = 4, Dm = 1.161 gm·cm−3, Dc = 1.172gm·cm−3, μ= 0.072cm−1, F000 = 304, (MoKα) = 0.71069 A, final R1 and wR2 are 0.0548 and 0.1526 respectively. Hydrogen bonds of the type CH···N and NH···N are observed in this structure. The hydrogen bonded molecules are stacked in layers when viewed along b.

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.

Kinetic studies on the oxidation of two basic amino acids (AA), L-lysine and L-histidine, by manganese(III) ions have been performed in pyrophosphate solution at 328 K and pH 1.3. Manganese(III) pyrophosphate solution was prepared by a known chemical method and the nature of the oxidizing species present in the solution was determined by spectrophotometric and redox potential measurements. The reaction follows the rate law: rate = k [Mn(III)] [AA] [H+][x/[Mn(II)]y [P2O7 4−]z] where x, y, and z are all fractional. The effects of added anions, fluoride, chloride, and perchlorate, and of varying solvent composition were studied. A solvent isotope effect in D2O medium was investigated. The dependence of the rate on temperature was studied and activation parameters were evaluated from the Arrhenius and Eyring plots. A mechanism, which is consistent with the kinetic data, has been discussed.

The kinetics and mechanism of oxidation of threose-series hexoses and pentoses by chloramine-T in alkaline medium was investigated. Kinetic studies with d -galactose, d -sorbose, d -xylose, and d -lyxose showed that the rate of the reaction was first order with respect to sugar and chloramine-T, and second order with respect to hydroxide ion. p-Toluenesulfonamide and chloride ions, the reduced products of chloramine-T, have no effect on the reaction rate. The rate increases with increase in ionic strength of the medium, and the dielectric effect is negative. Proton inventory studies in H2O–D2O mixtures suggested a single transition state. Product analysis for d -gulose, d -idose, l -sorbose, d -galactose, d -talose, d -tagatose, d -xylose, and d -lyxose revealed that all lyxose-series hexoses gave mainly mixtures of lyxonic and threonic acids with minor proportions of hexonic, xylonic and glyceric acids, whereas all xylose-series hexoses gave mixtures of lyxonic, threonic and glyceric acids with minor amounts of xylonic and hexonic acids. Xylose and lyxose gave mixtures consisting mainly of lyxonic, threonic, and glyceric acids with minor proportions of xylonic acid. From the results of kinetic studies, reaction stoichiometry, and product analysis, a possible mechanism for the oxidation of threose-series sugars with chloramine-T is suggested.

Nitrogen-centered radicals have been generated upon electron transfer from the corresponding (1b~, 2b~, 3b~, 4b~) stable nitrenium ions (1b`, 2b`, 3b`, 4b`) and characterized by electrochemistry and simultaneous spectro-electrochemistry. Reactivity of the radicals is strongly inNuenced by the substituents attached to the two nitrogen atoms that are directly linked to the ion nitrenium center. While and are stable on the timescale 1b~ 2b~ of the electrochemical experiment, and have half-lifetimes of 3b~ 4b~ ca. 1.2E1.25 and 0.9E1 ls, respectively, in acetonitrile, as determined with ultramicroelectrodes. Redox properties of the nitrenium ion/radical couples and relative stability of the radicals are discussed in light of both experimental results and ab initio calculations

The kinetics and mechanism of oxidation of D-glucose, D-mannose, D-fructose, D-arabinose, and D-ribose with chloramine-T in alkaline medium were studied. The rate law, rate = k [Chloramine-T] [Sugar] [HO-]2, was observed. The rate of the reaction was influenced by a change in ionic strength of the medium, and the dielectric effect was found to be negative. The latter enabled the computation of dAB, the size of the activated complex. The reaction rate was almost doubled in deuterium oxide. Activation energies were calculated from the Arrhenius plots. HPLC and GLC-MS analyses of the products indicated that the sugars were oxidized to a mixture of aldonic acids, consisting of arabinonic, ribonic, erythronic, and glyceric acids. Based on these data, a plausible mechanism involving the aldo-enolic anions of pentoses and keto-enolic anions of hexoses is suggested.

In the title compound, C8H7N3O2S, the dihedral angle between the 1,2,4-triazole ring and the phenyl ring is 82.17 (14)degrees. The geometry around the S atom is distorted tetrahedral. The molecules are linked by intermolecular C-H center dot center dot center dot N and C-H center dot center dot center dot O hydrogen bonds.

The novel bioactive compound 4-(3,4-dichlorophenyl)-2-(3,4,5-trimethoxy-benzylidene)-3,4-dihydro-naphthalen-1(2 H)-one was synthesised in three different methods, namely, conventional, MW irradiation with solvent and MW irradiation without solvent. The synthesised compound was characterised by spectroscopic techniques and finally confirmed by X-ray crystal structure analysis.

In the crystal structure of the title compound, C17H19NO4, the geometry about the C=N double bond is Z. The structure is stabilized by weak inter­molecular C—H⋯O hydrogen bonds, linking the mol­ecules into chains.

A new dipolarophile for the construction of the bioactive title compound, C18H18N2O, was synthesized by base-catalysed reaction of benzaldehyde with (4-methoxy­phen­yl)acetonitrile. The olefinic bond connecting the (4-methoxy­phen­yl)acetonitrile and the dimethyl­amino­phenyl groups has a Z geometry.

A new dipolarophile for the construction of bioactive isoxazoli(di)nes, (Z)-2-(4-methoxy­phen­yl)-3-phenyl­acrylo­nitrile, C16H13NO, was synthesized by the base-catalysed reaction of benzaldehyde with 4-methoxy­phenyl­acetonitrile. The olefinic bond connecting the 4-methoxy­phenyl­acetonitrile and the phenyl groups has Z geometry. There are two mol­ecules in the asymmetric unit. In the crystal structure, the mol­ecules are linked by C—H⋯O hydrogen bonds.