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Hydrolysis Kinetics (hydrolysis + kinetics)
Selected AbstractsControlled Release of Perfumery Alcohols by Neighboring-Group Participation.HELVETICA CHIMICA ACTA, Issue 8 20032-(Hydroxymethyl)-, 2-Carbamoylbenzoates, Comparison of the Rate Constants for the Alkaline Hydrolysis of 2-Acyl- A series of 2-acylbenzoates 1 and 2, 2-(hydroxymethyl)benzoates 3, 2-carbamoylbenzoates 4,6, as well as the carbamoyl esters 7 or 8 of maleate or succinate, respectively (see Fig.,2), were prepared in a few reaction steps, and the potential use of these compounds as chemical delivery systems for the controlled release of primary, secondary, and tertiary fragrance alcohols was investigated. The rate constants for the neighboring-group-assisted alkaline ester hydrolysis were determined by anal. HPLC in buffered H2O/MeCN solution at different pH (Table,1). The rates of hydrolysis were found to depend on the structure of the alcohol, together with the precursor skeleton and the structure of the neighboring nucleophile that attacks the ester function. Primary alcohols were released more rapidly than secondary and tertiary alcohols, and benzoates of allylic primary alcohols (e.g., geraniol) were hydrolyzed 2,4 times faster than their homologous saturated alcohols (e.g., citronellol). For the same leaving alcohol, 2-[(ethylamino)carbonyl]benzoates cyclized faster than the corresponding 2-(hydroxymethyl)benzoates, and much faster than their 2-formyl and 2-acetyl analogues (see, e.g., Fig.,4). Within the carbamoyl ester series, 2-[(ethylamino)carbonyl]benzoates were found to have the highest rate constants for the alkaline ester hydrolysis, followed by unsubstituted 2-(aminocarbonyl)benzoates, or the corresponding isopropyl derivatives. To rationalize the influence of the different structural changes on the hydrolysis kinetics, the experimental data obtained for the 2-[(alkylamino)carbonyl]benzoates were compared with the results of density-functional computer simulations (Table,2 and Scheme,4). Based on a preliminary semi-empirical conformation analysis, density-functional calculations at the B3LYP/6-31G** level were carried out for the starting precursor molecules, several reaction intermediates, and the cyclized phthalimides. For the same precursor skeleton, these simple calculations were found to model the experimental data correctly. With an understanding of the influence of structural parameters on the rate constants obtained in this work, it is now possible to influence the rates of hydrolysis over several orders of magnitude, to design tailor-made precursors for a large variety of fragrance alcohols, and to predict their efficiency as controlled-release systems in practical applications. [source] Comparison of the hydrolytic stability of S -(N,N -diethylaminoethyl) isobutyl methylphosphonothiolate with VX in dilute solutionJOURNAL OF APPLIED TOXICOLOGY, Issue S1 2001M. D. Crenshaw Abstract The stability of S -(N,N -diethylaminoethyl) isobutyl methylphosphonothiolate,a V-type nerve agent developed by the former Soviet Union,in the environment is an important parameter in threat assessment analysis and for the determination of use, production, testing and storage of this chemical warfare agent. S -(N,N -Diethylaminoethyl) isobutyl methylphosphonothiolate is a structural isomer of the nerve agent VX developed by the USA and the UK and will be referred to as VXA (VX analog) in this presentation. Because VXA and VX differ structurally, even though they do have the same molecular formula, it is expected that their physical and chemical properties would be different. This preliminary investigation was undertaken to determine the relative hydrolysis rate of VXA compared with VX. The hydrolysis of each compound at approximately 1 mg ml,1 in unbuffered water at pH 7 was determined side-by-side. The half-lives for VXA and VX were determined to be 12.4 days and 4.78 days, respectively. Agent VXA hydrolyzed 2.6 times more slowly than VX, and each agent followed second-order hydrolysis kinetics. These results imply that VXA is more persistent in the environment and therefore poses a greater threat. These results also imply that VXA is more likely to be detected, if present, during an inspection in support of the Chemical Weapons Convention. Copyright © 2001 John Wiley & Sons, Ltd. [source] Characterization and modelling of denim-processing wastewaters for activated sludgeJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 9 2001Derin Orhon Abstract The study involved characterization of denim-processing wastewaters, mainly to generate the necessary experimental data for the modelling and evaluation of the activated sludge process. The striking feature of the wastewater quality was the excessive suspended solids content requiring effective removal before biological treatment. COD fractionation was, however, typical for a textile effluent in general, with a biodegradable fraction of 90%, a readily biodegradable COD ratio of 20%, a predominantly soluble slowly biodegradable fraction of 55,60% and negligible particulate inert COD. Hydrolysis was identified as the significant step in the biodegradation kinetics with rate coefficients quite specific to plant operation. Evaluation of the hydrolysis kinetics showed that the magnitude of the slowly biodegradable COD could be reduced with a higher hydraulic detention time, effectively improving the quality of the soluble effluent. © 2001 Society of Chemical Industry [source] Stability and hydrolysis kinetics of spirosuccinimide type inhibitors of aldose reductase in aqueous solution and retardation of their hydrolysis by the target enzymeJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2008Masuo Kurono Abstract The stability and the hydrolysis kinetics of spirosuccinimide type aldose reductase (AR) inhibitors, SX-3030 (racemate) and its optical enantiomers (R - and S -isomers), were investigated in aqueous solution. The hydrolysis followed pseudo-first-order kinetics and showed significant pH dependence. Maximum solution stability was observed below pH 2.4, whereas the hydrolysis was gradually catalyzed by hydroxide ion at neutral to alkaline pH while the compounds exhibiting moderate pH-independent stability at acidic to neutral conditions (pH 4,7) to enable oral administration. A pK of 3.7 was obtained from the pH-rate profile, but this kinetically derived pK is approximately 2 pH units below the pK of the parent compounds, suggesting the presence of an acidic intermediate involved in the hydrolysis process. These findings, together with structural analysis, support the notion that the hydrolysis would proceed via nucleophilic attack of a water molecule or hydroxide ion on the scissile carbonyl bond of the succinimide ring to form a succinamic acid intermediate that has a ,-keto acid structure, followed by decarboxylation to give a racemized succinimide ring-opened product. On the other hand, the interconversion of the R - and S -isomers did not occur during hydrolysis; however, the hydrolysis of the R -isomer was markedly suppressed by the target enzyme AR whereas that of the S -isomer was not, indicating a high degree of complementarity of interacting surfaces between the R -isomer and the enzyme. The results in the present study could provide useful clues for facilitating the appropriate stabilization strategies as well as for evaluating the pharmacological effects on target tissues in vivo, and suggested that the R -isomer may be a suitable candidate as AR inhibitor. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:1468,1483, 2008 [source] Liposome transport of hydrophobic drugs: Gel phase lipid bilayer permeability and partitioning of the lactone form of a hydrophobic camptothecin, DB-67JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2008Vijay Joguparthi Abstract The design of liposomal delivery systems for hydrophobic drug molecules having improved encapsulation efficiency and enhanced drug retention would be highly desirable. Unfortunately, the poor aqueous solubility and high membrane binding affinity of hydrophobic drugs necessitates extensive validation of experimental methods to determine both liposome loading and permeability and thus the development of a quantitative understanding of the factors governing the encapsulation and retention/release of such compounds has been slow. This report describes an efflux transport method using dynamic dialysis to study the liposomal membrane permeability of hydrophobic compounds. A mathematical model has been developed to calculate liposomal membrane permeability coefficients of hydrophobic compounds from dynamic dialysis experiments and partitioning experiments using equilibrium dialysis. Also reported is a simple method to study the release kinetics of liposome encapsulated camptothecin lactone in plasma by comparing the hydrolysis kinetics of liposome entrapped versus free drug. DB-67, a novel hydrophobic camptothecin analogue has been used as a model permeant to validate these methods. Theoretical estimates of DB-67 permeability obtained from the bulk solubility diffusion model and the "barrier-domain" solubility diffusion model are compared to the experimentally observed value. The use of dynamic dialysis in drug release studies of liposome and other nanoparticle formulations is further discussed and experimental artifacts that can arise without adequate validation are illustrated through simulations. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:400,420, 2008 [source] | ||||||||||