Characterization of Ester Hydrolysis in Terms of Microscopic Rate Constants

Abstract

Hydroxide-catalyzed ester hydrolysis for molecules of coexisting species is quantitated in terms of microscopic rate constants, a new, species-specific physicochemical parameter. Relationships between the overall and component reactions, as well as the macroscopic and microscopic rate constants are deduced. Experimental techniques, evaluation methods, and feasibility are discussed. Species-specific, pH-independent rate constants of four coexisting, differently hydrolyzing microspecies are determined for the first time. Protonation of an alpha-amino and beta-imidazolyl site in amino acid esters has been found to accelerate the hydroxide-catalyzed hydrolysis by factors of 120 and 7.5, respectively, whereas they jointly exert a nearly 3000-fold acceleration. A total of 20 microscopic protonation equilibrium constants, as component parameters in the rate equations, have also been determined. The species-specific rate constants have been found to correlate with the site- and species-specific basicity of the leaving group and the NMR chemical shift of an adjacent proton. Individual contributions of the various microforms to the overall hydrolysis rate are depicted in microscopic reaction fraction diagrams.

Advances in microspeciation of drugs and biomolecules: Species-specific concentrations, acid-base properties and related parameters

“…Superscripts of microconstants indicate the group protonating in the given microequilibrium protonation process, whereas the subscript (if any) stands for the group already holding proton during the process. 5-HT -, H5-HT and H25-HT + are macrospecies, of which H5-HT is a composite of two protonation isomer microspecies, a non-charged ( 0 HT -H5 ) and a zwitterionic ( (6) The concentration ratio of protonation isomers (often called kz, the tautomeric ratio) is independent of both the pH and the total concentration:…”

“…Microscopic thermodynamic parameters are essential to understand a wide variety of chemical phenomena, including drug delivery [1], self-assembly [2], ligand−receptor interactions [3], folding kinetics [4], chemical reaction networks [5], the rate of hydrolysis reactions [6].…”

Reactions of Carboxylic, Phosphoric and Sulfonic Acids and their Derivatives

“…Such rate constants take account of the various protonation states of the basic site(s) adjacent to the ester group, and they have been determined for the hydroxidecatalysed ester hydrolysis of phenylalanine methyl ester (7) and histidine methyl ester (8), which possess one and two adjoining basic groups, respectively, and yield two and four, respectively, microscopic rate constants. 9 In a review of nucleophile isotope effects in chemistry, the hydrolysis of formates was discussed. 10 The effect of dioxane on the acid-catalysed hydrolysis of ethyl formate was studied by carrying out the reaction in 0-80% (v/v) dioxane at different temperatures ranging from 20 to 40 • C. It was proposed that up to 1.5 mol of water are associated with the activated complex.…”

“…The possibility that the pendant amines deprotonated second-sphere water molecules to make them more nucleophilic was also proposed. 107 The cleavage rates of UpU and the p-nitrophenyl analogue UpPNP (106) were used to study the catalytic mechanism of a previously studied di(zinc [9]ane-N3) complex (107). Greater transition state stabilization during the cleavage of UpU compared with UpPNP was found, which was attributed to stabilizing interactions between the catalyst and the alkoxy leaving group attached to C (5 ) A series of heptameric single-stranded (ss) DNAs and RNAs having a central 9guanylate ion have been investigated by 31 P NMR spectroscopy in order to determine its effect on each of the flanking phosphate moieties.…”

Exploring the boundaries of direct detection and characterization of labile isomers – a case study of copper(ii)–dipeptide systems

“…It determines their ability to recognize substrates, provide reactive sites by transactivation, electrostatically activate the substrate, generate nucleophile agents in hydrolytic reactions, or stabilize either the transition state or the products. [15][16][17][18][19][20][21][22][23][24][25][26] The binding mode of metal ions greatly influences the conformation of ligands 27,28 and vice versa. The change in the protein structure induced by metal binding may lead to functional [29][30][31][32][33][34][35] or pathogenic [36][37][38][39][40][41][42][43][44] complexes.…”