Equilibrium deuterium isotope effects on the ionization of thiol acids

Abstract

Isotope effects on the ionization of the thiol groups of pentafluorothiophenol, thioacetic acid, 4-nitrothiophenol, thiophenol, methyl mercaptoacetate, mercaptoethanol, and mercaptoacetate in water and deuterium oxide range from íTrsh/^rsd = 2.0-2.5 and approximately follow the equation ApK = 0.26 + 0.012pA% Bending as well as stretching frequencies contribute significantly to the isotope effects for reactions of thiols. The increase in the isotope effect with decreasing acidity of the thiol and the magnitude of the difference in the isotope effects for the ionization of RSH and ROH provide evidence that isotope effects on the interaction of RSand ROwith the solvent contribute significantly to the observed effects.Human Development of the National Institutes of Health (HD 01247).

Reactivities of neutral and cationic forms of 2,2′-dipyridyl disulphide towards thiolate anions. Detection of differences between the active centres of actinidin, papain and ficin by a three-protonic-state reactivity probe

“…1(a). The kinetically determined pKa of 9.63 corresponds to the pKa value of 2-mercaptoethanol (9.64 ± 0.03) determined by study of the pHdependence of thiolate ion absorbance at 237nm and is in good agreement with the value (9.61) reported by Jencks & Salvensen (1971). Spectral analysis of solutions of 2,2'-dipyridyl disulphide in the pH range-1 to 7 at 300nm and at 290nm confirmed the value of pKaii reported by Brocklehurst & Little (1973) as 2.45 and provided a value of pKai of 0.35.…”

Kinetic Isotope Effects in Enzymology

“…Although the p K of an ionizing residue is most often 0.4-0.6 pH units higher in D2O than HzO, the fractionation factor for an active site residue cannot be assumed to be unip. In the case of an active site -SH, ApK may be small (202,203,59). Recent studies of solvent isotope effects in two metalloenzymes suggest that ApK may be less than 0.4-0.6 for the ionization of water in the inner coordination sphere of a metal (60,61).…”

Mechanistic change in the reactivity of substituted phenyl acetates over phenyl thiolacetates toward imidazole in aqueous phase

“…Bruice et al have shown that the alkyl thiolacetates and thiolactones which are subject to general catalysis of nucleophilic attack of primary and secondary amines usually are as sensitive to general acid catalyzed attack as to general base catalyzed attack in the presence of conjugate acid form of the nucleophile 56. Jencks and Salvesen have observed a general acid assisted path in the reactions of acetylimidazole with weakly acidic thiols, and further argued that similar case should be observed for the reverse reaction, which is the reaction of imidazole with thiol esters 57. It has been suggested that in the papain‐catalyzed hydrolysis of esters, to form an acyl‐enzyme intermediate by acylation of −SH group in the active site of the enzyme, the rate‐determining step was the breakdown of an anionic tetrahedral intermediate through general acid catalysis by a neighboring imidazolium ion 58.…”