Kallol K. Ghosh

Physicochemical Properties and Supernucleophilicity of Oxime-Functionalized Surfactants: Hydrolytic Catalysts toward Dephosphorylation of Di- and Triphosphate Esters

Aggregation and kinetic studies have been performed to understand the hydrolytic potencies of the series of oxime-functionalized surfactants, viz., 3- hydroxyiminomethyl-1-alkylpyridinium bromide (alkyl = CnH2n+1, n = 10, 12, 14, 16, 18) in the cleavage of phosphate esters, p-nitrophenyl diphenyl phosphate (PNPDPP) and bis(2,4-dinitrophenyl) phosphate (BNDPP), in mixed micelles with cetylpyridinium bromide (CPB). Micellization and surface properties of mixed micelles functional surfactants with CPB were studied by conductivity and surface tension measurements. Acid dissociation constants (pKa) were determined, the effect of functional surfactant alkyl chain length and pH on the observed rate constant (kobs) for phosphate ester cleavage has been discussed, and the effect of substrate on the supernucleophilicities of the studied oximes was monitored. Functionalized oxime-based surfactants were proved to be supernucleophiles to attack on the P═O center of tri- and diphosphate esters. Oximes with hexadecyl alkyl chain length (3-C16) showed maximum micellar effect on the rate constants toward PNPDPP. Micellar effects were analyzed in terms of the pseudophase model.

Development and Structural Modifications of Cholinesterase Reactivators against Chemical Warfare Agents in Last Decade: A Review

Organophosphate (OP) pesticides and nerve agents are responsible for suicidal and accidental poisonings. The acute toxicity of nerve agents leads to progressive inhibition of the enzyme acetylcholinesterase (AChE) by phosphylation of serine residue at the active site of gorge. The recent massive destruction of Syrian civilians by nerve gas sarin, has again renewed the research attention of global science fraternity towards nerve agents, their mode of action and most prominently their therapeutic treatment. This review is principally focused on nerve agent intoxication. The common approach to deal with OP-intoxication is, application of antimuscarinic drug (atropine), anticonvulsant drug (diazepam) and clinically used oximes (pralidoxime, trimedoxime, obidoxime and asoxime). However, the existing therapeutic approach is arguable and has several failings to cure all kinds of nerve agent poisonings. Considering this issue, numerous oximes have been synthesized and screened through various in-vitro and in-vivo studies in last decade to overcome the downsides. At present, only a few oximes (bis pyridinum-oximes) exhibit sound efficacy against selective OPs. In spite of extensive efforts, till date no oxime is available as a universal antidote against all the classes of OPs. This review is centered on the recent developments and structural modification of AChE reactivators against nerve agent toxicity. In particular, a deeper look has been taken into chemical modifications of the reactivators by incorporation of different structural moieties targeted towards the increased reactivation affinity and improved blood brain barrier (BBB) penetration.

Nucleophilic attack of salicylhydroxamate ion at C=O and P=O centers in cationic micellar media.

The reaction between the salicylhydroxamate anion (SHA(-)) and p-nitrophenyl benzoate (PNPB), tris(3-nitrophenyl)phosphate (TRIS), and bis(2,4-dinitrophenyl)phosphate (BDNPP) have been examined kinetically. The α-nucleophile, SHA(-), incorporated into cetyltrimethylammonium bromide (CTAB) micelles accelerates dephosphorylation of tris(3-nitrophenyl)phosphate (TRIS) over the pH range 6.7-11.4. With a 1.0 mM of SHA in CTAB, the nucleophilicity of SHA followed the order of reactivity, PNPB (C=O, carboxylate ester) > TRIS (P=O, triester) > BDNPP (P=O, diester), and monoanionic SHA(-) and dianionic SA(2-) are the reactive species. The critical micelle concentration, cmc, of cetyltrimethylammonium bromide (CTAB) decreases and the fractional ionization constant, α, increases with increasing the concentration of SHA(-). Addition of 1 and 10 mM SHA under the reaction conditions (pH 9.2, borate buffer) led to saturation of the micellar surface and provided qualitative information for the micellar incorporation of hydroxamate ion. Plots of the pseudo-first-order rate constant, k(obs), log k(obs), fraction of hydroxamic acid ionized, α(SHA(-)) and α(SA(2-)), vs pH showed bifunctional nucleophilicity of hydroxamic acid under micellar condition. Plotting k(obs) vs [SHA](T) gave a straight line with intercept k(0). This indicates that hydroxamate ions are very strong nucleophiles for nucleophilic attack at the C and P center. The pseudo-first-order rate constant-surfactant profiles show micelle-assisted bimolecular reactions involving interfacial ion exchange between bulk aqueous media and micellar pseudophase.

Oxime K027: novel low-toxic candidate for the universal reactivator of nerve agent- and pesticide-inhibited acetylcholinesterase

Oxime K027 is a low-toxic bisquaternary compound originally developed as a reactivator of acetylcholinesterase (AChE) inhibited by nerve agents. The reactivation potency of K027 has been tested as a potential reactivator of AChE inhibited by tabun, sarin, cyclosarin, soman, VX, Russian VX, paraoxon, methylchlorpyrifos, and DDVP. The results show that oxime K027 reactivated AChE inhibited by almost all tested inhibitors to more than 10%, which is believed to be enough for saving the lives of intoxicated organisms. In the case of cyclosarin- and soman-inhibited AChE, oxime K027 did not reach sufficient reactivation potency.

In vitro reactivation kinetics of paraoxon- and DFP-inhibited electric eel AChE using mono- and bis-pyridinium oximes

Abstract Oxime-assisted reactivation of organophosphate (OP)-inhibited acetylcholinesterase (AChE) is a crucial step in the post-inhibitory treatment of OP intoxication. The limited efficacy of oxime reactivators for all OP nerve agents and pesticides led to the development of various novel oximes and their thorough kinetic investigations. Hence, in the present investigation, we have tested 10 structurally different pyridinium oxime-based reactivators for their in vitro potency to reactivate paraoxon- and DFP-inhibited electric eel AChE. From structure activity relationship point of view, various oximes such as mono-quaternary (2-PAM, K100, K024) and bis-quaternary symmetric (obidoxime, TMB-4) and asymmetric (K027, K048, K203, K618, K628) oximes bearing different connecting linkers (oxybismethylene, trimethylene, propane, butane, butene, and xylene) have been studied. The observed kinetic data demonstrate that not only the position of oxime group is decisive for the increased reactivation ability of oximes, but the role of connecting linker is also significant. Oximes with aliphatic linkers are superior reactivators than the oximes with unsaturated and aromatic linkers. The optimal chain length for plausible reactivation ability for paraoxon- and DFP-inhibited AChE is 3 or 4 carbon–carbon connecting linker between prydinium rings.

Progress in drug development for Alzheimer's disease: An overview in relation to mitochondrial energy metabolism

Current possibilities of Alzheimers disease (AD) treatment are very limited and are based on administration of cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and/or N-methyl-d-aspartate receptor antagonist, memantine. Newly synthesized drugs affect multiple AD pathophysiological pathways and can act as inhibitors of cholinesterases (AChE, BuChE), inhibitors of monoamine oxidases (MAO-A, MAO-B), modulators of mitochondrial permeability transition pores, modulators of amyloid-beta binding alcohol dehydrogenase and antioxidants. Effects of clinically used as well as newly developed AD drugs were studied in relation to energy metabolism and mitochondrial functions, including oxidative phosphorylation, activities of enzymes of citric acid cycle or electron transfer system, mitochondrial membrane potential, calcium homeostasis, production of reactive oxygen species and MAO activity.

Spectrofluorometric Determination of Mercury and Lead by Colloidal CdS Nanomaterial

Heavy metal ions such as Hg and Pb are hazardous due to very high toxicity, mobility, and ability to accumulate through the food chain or atmosphere in the environment system. Therefore, ultrasensitive determination of mercury and lead is important to provide an evaluation index of ions in aqueous environment. This paper describes the investigation of surface modified quantum dots (QDs) as a sensing receptor for Hg2+ and Pb2+ ion detection by optical approach. Water-soluble L-cysteine-capped CdS QDs have been synthesized in aqueous medium. These functionalized nanoparticles were used as a fluorescence sensor for Hg2+ and Pb2+ ions, involved in the fluorescence quenching. The effect of foreign ions on the intensity of CdS QDs showed a low interference response toward other metal ions except Cu2+ and Fe2+ ions. The limit of detection (LOD) of this system is found to be 1.0 and 3.0 nM for Hg2+ and Pb2+ ions, respectively. GRAPHICAL ABSTRACT

Microemulsions as Reaction Media for a Hydrolysis Reaction

The kinetics of the acidic hydrolysis of N-hydroxyphthalimide (phthalomohydroxamic acid) have been studied in microemulsions of three components (Aerosol OT (AOT)/isooctane/water) at 328 K. The effect of significant parameters such as water/AOT mole ratio (ω) and AOT concentration were analyzed. The reaction rate is higher in microemulsions than in conventional aqueous solution. In all cases pseudo first-order kinetics were observed. Activation parameters have been obtained from the temperature dependence of the rate constant in the microemulsion.

Effects of Electrolytes on Micellar and Surface Properties of Some Monomeric Surfactants

Micellar and surface properties of cationic surfactants, that is, cetyldiethylethanolammonium bromide (CDEEABr), cetyldimethylethanolammonium bromide (CDMEABr), cetyltrimethylammonium bromide (CTAB), and tetradecyldiethylethanolammonium bromide (TDEEABr) in the presence of sodium halide (NaCl, NaBr, and NaI) have been investigated by conductivity and surface tension measurements at 300 K. The critical micelle concentration (cmc) and interfacial parameters, such as the maximum surface excess (Гmax), minimum area per molecule (Amin) and surface pressure at the cmc (πcmc) were computed from the surface tension data. The effects of chain length of cationic surfactants in absence and presence of salts have also been studied. The cmc and degree of micellar ionization (α) values were found to decrease with an increase concentration of salts and values decrease in the order NaCl <NaBr <NaI. Thermodynamic parameters, standard Gibbs free energy of micellization (ΔG°m) and adsorption at air/water interfaces (ΔG°ads) were also evaluated.

Micellar kinetics of hydrolysis of hydroxamic acids in zwitterionic sulfobetaine surfactants

Abstract The effect of zwitterionic micelles of dodecyldimethylammonio-propane-sulfonate (SB3-12) and hexadecyl-dimethyl-ammonio-propanesulfonate (SB3-16) [C n H 2 n +1 N + Me 2 (CH 2 ) 3 SO 3 − , SB3- n , n =12, 16] on the acid and alkaline hydrolyses of some C- and N-substituted hydroxamic acids (RCON(OH)R′) have been studied at 55°C in 5% (v/v) dioxane medium. For acid hydrolysis zwitterionic micelles inhibit the reaction whereas for alkaline hydrolysis, zwitterionic micelles accelerate the rate of hydrolysis. Kinetic data corresponding to the reaction with micelles are analyzed by using the Menger and Portnoy model. Binding constant and first order rate constant for the reaction in micellar pseudophase and in water obtained from kinetic analysis, are reported.