Hydrophobicity dependence of oxidation of tetrapeptides of elastin sequences with Mn(III): Synthesis,characterization, kinetics,and mechanistic study

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 λ_max = 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     

Some analytical applications of aromatic sulfonyl haloamines: Estimation of indigocarmine by chloramine-B,bromamine-T,and dibromamine-T

Sodium N-chlorobenzenesulfonamide (chloramine-B, CAB), sodium N-bromo-p-toluenesulfonamide (bromamine-T, BAT) and N,N′-dibromo-p-toluenesulfonamide (dibromamine-T, DBT) are employed as analytical reagents for estimating indigocarmine (IC) in solution. A four-electron stoichiometry is observed within 30 min in the following media: CAB, 0.1–1.0 N HCl or H₂SO₄ and pH 1 buffer; BAT, 0.01–0.10 N NaOH; DBT, glacial acetic acid. The back titration methods are fairly rapid, simple, and accurate. The product of oxidation, isatinsulfonate, was estimated by spectrophotometric measurements at 410 nm. The sulfonamides formed by reduction of the haloamines are detected by TLC and paper chromatography.     

Convenient synthesis of novel N-(5-allyl-7,7-difluoro)-4,5,6,7-tetrahydro-2H-indazol-3-yl)-carboxymides

5-Allyl-7,7-difluoro-2-(2,4-difluorophenyl)-6-(4-methoxyphenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-3-amine represents a fluorinated heterocyclic scaffold, potentially attractive. It was synthesized via Michael addition, Mannich reaction of the difluorinated ethyl bromoacetate with a benzotriazole derivative, followed by a Dieckmann condensation. Starting from simple materials, this efficient route which gives access to novel functionalized N-(5-allyl-7,7-dihalo)-4,5,6,7-tetrahydro-2H-indazol-3-yl)-carboxymides, was explored and adapted for parallel synthesis, resulting in a compound library.     

Design and Activity of Novel Oxadiazole Based Compounds That Target Poly(ADP-ribose) Polymerase

Novel PARP inhibitors with selective mode-of-action have been approved for clinical use. Herein, oxadiazole based ligands that are predicted to target PARP-1 have been synthesized and screened for the loss of cell viability in mammary carcinoma cells, wherein seven compounds were observed to possess significant IC₅₀ values in the range of 1.4 to 25 µM. Furthermore, compound 5u, inhibited the viability of MCF-7 cells with an IC₅₀ value of 1.4µM, when compared to Olaparib (IC₅₀ = 3.2 µM). Compound 5s also decreased cell viability in MCF-7 and MDA-MB-231 cells with IC₅₀ values of 15.3 and 19.2 µM, respectively. Treatment of MCF-7 cells with compounds 5u and 5s produced PARP cleavage, H2AX phosphorylation and CASPASE-3 activation comparable to that observed with Olaparib. Compounds 5u and 5s also decreased foci-formation and 3D Matrigel growth of MCF-7 cells equivalent to or greater than that observed with Olaparib. Finally, in silico analysis demonstrated binding of compound 5s towardsthe catalytic site of PARP-1, indicating that these novel oxadiazoles synthesized herein may serve as exemplars for the development of new therapeutics in cancer.     

Oxidation of L‐amino acids by metal ion (Mn3+) in sulfuric acid medium: Effect of nucleophilicity and hydrophobicity on reaction rate

The kinetics of oxidation of L ‐amino acids (AAs) glycine( 1a ), alanine( 1b ), valine( 1c ), isoleucine( 1d ), leucine( 1e ), proline( 1f ), and phenylalanine( 1g ) by a transition metal ion (Mn³⁺) was studied in the presence of sulfuric acid medium at 26°C by a spectrophotometrical (λ_max = 500 nm) method. In all cases, the kinetics of reactions was of first‐order with respect to each [AA] and [Mn³⁺]. Increased [H⁺], [Mn²⁺] (the reduction product of Mn³⁺), sulfate, and chloride had no effect on the reaction rate. However, the reaction rate increased with increased dielectric constant of the medium. Oxidation rate increased for 1a–g and an apparent correlation was observed between the rate of oxidation and nucleophilicty of AAs except for 1a and 1g . The reaction rate also linearly depended on the hydrophobicity of AAs except for 1f and 1g . The thermodynamic parameters for AA‐metal ion complex formation and activation parameters for the rate‐limiting steps have been evaluated. Analysis of the oxidation products indicated that the AAs underwent oxidative deamination and decarboxylation to form corresponding aldehydes. Based on these data, plausible mechanisms involved in the oxidation of AAs are proposed. © 2011 Wiley Periodicals, Inc. Int J Chem Kinet 43: 599–607, 2011     

Kinetic and mechanistic studies of oxidation of arginine,histidine, and threonine in alkaline medium by N-chloro-N-sodio-p-toluenesulfonamide

The kinetics of oxidation of arginine, histidine, and threonine by chloramine-T (CAT) have been investigated in alkaline medium at 35°C. The rates are first order in both [CAT] and [amino acid] and inverse fractional order in [OH^?] for arginine and histidine. The rate is independent of [OH^?] for threonine. Variation of ionic strength and addition of the reaction product, p-toluenesulfonamide, or Cl^? ions had no effect on the rate. A decrease of the dielectric constant of the medium by adding methanol decreased the rate with arginine, while the rates increased with histidine and threonine. The solvent isotope effect was studied using D₂O. (k_obs)/(k_obs) was found to be 0.55 and 0.79 for arginine and histidine, respectively. The reactions were studied at different temperatures, and activation parameters have been computed. The oxidation process in alkaline medium, under conditions employed in the present investigations, has been shown to proceed via two paths, one involving the interaction of RNHCl (formed rapidly from RNCl^?), with the amino acid in a slow step to form monochloroamino acid, which subsequently interacts with another molecule of RNHCl in a fast step to give the products, p-toluenesulfonamide (RNH₂), and the corresponding nitrile of the amino acid (R'CN). The other path involves the interaction of RNCl^? with the amino acid in a similar way to give RNH₂ and R'CN. Mechanisms proposed and the derived rate laws are consistent with the observed kinetics. The rate constants predicted using the derived rate laws, as [OH^?] varies, are in excellent agreement with the observed rate constants, thus justifying these rate laws and hence the proposed mechanistic schemes.     

One-pot approach for the synthesis of 2-aryl benzothiazoles via a two-component coupling of gem-dibromomethylarenes and o-aminothiophenols

One-pot synthesis of 2-aryl benzothiazoles from gem-dibromomethylarenes using 2-aminoarylthiols is described. Benzothiazoles were obtained in high chemical yields under mild conditions. This transformation would facilitate synthesis by short reaction times, large-scale synthesis, easy and quick isolation of the products, which are the main advantages of this procedure.     

Kinetics and mechanism of oxidation of some aliphatic esters by sodium N-bromo-p-toluenesulfonamide

The kinetics of oxidation of methyl, ethyl, n-propyl, isopropyl, and n-butyl acetates to acetic acid and the corresponding aldehyde by the title oxidant in aqueous HCl medium at 40°C has been studied. The reaction shows first-order with respect to [oxidant] and fractional orders in [H⁺] and [ester]. An isokinetic relationship was observed with β = 374 K indicating enthalpy as the rate controlling factor. Attempts have been made to arrive at a linear free energy relationship through the Taft treatment. Electron releasing groups in the ester moiety increase the rate with ρ* = ?9.88. A two-pathway mechanism, consistent with the observed kinetic data, has been proposed. © 1993 John Wiley & Sons, Inc.