Leaving group effects in thiolester hydrolysis. Part 2. On the possibility of an elimination–addition (keten) mediated pathway in S-acetylcoenzyme a basic hydrolysis and acetyl transfer

Abstract

Alkaline hydrolysis rates (kwo-) at 25 "C in aqueous solution for a series of S-alkyl and S-aryl thiolacetates, including S-acetylcoenzyme A, were correlated (as their logarithms) with the pKa of the conjugate acid of the thiolate leaving group to give a slope (P,.J of -0.33. In comparison with the corresponding oxygen esters, thiolesters are, for rhe basicity of a given leaving species, one to two orders of magnitude iess reactive towards hydroxide ion and show little dispersion into aryl and alkyl leaving groups, ascribed to the lower steric sensitivity of thiolacetate esters compared with the oxygen analogues. The small value of PI . , . and the lower reactivity of Sthan O-esters are offered as evidence of a bimolecular associative (B,,2) mechanism for basic hydrolysis. The €2 route is excluded by the lack of deuterium incorporation into the (acetate) product of hydrolysis. In spite of the accepted acidity of thiolacetates, a kinetically insignificant amount of ester conjugate base is formed in aqueous solution even at high, non-physiological pH and thus S-acetylcoenzyme A does not hydrolyse by an E l CB pathway.

Kinetics and Mechanisms of Reactions of Thiol, Thiono, and Dithio Analogues of Carboxylic Esters with Nucleophiles

“…Douglas has extensively studied the hydrolysis of alkyl and aryl thiolacetates and thiolesters. , For the alkaline hydrolysis of thiolacetates, a linear Brönsted plot for the leaving thiolate group was found, with slope β lg = −0.33, similar to that obtained with oxygen esters but with a lower intercept than that for the oxy analogues. The lower reactivity of thiolacetates (compared to oxyacetates with isobasic leaving groups) and the similar β lg values suggest that the mechanism is the same for both classes of substrates, i.e., rate-determining formation of an anionic tetrahedral intermediate by OH - attack to the CO group . From the Brönsted plots it was also deduced that thiolacetates are as reactive toward OH - as oxyacetates bearing the same leaving group (except for the O or S atom).…”

“…From the Brönsted plots it was also deduced that thiolacetates are as reactive toward OH - as oxyacetates bearing the same leaving group (except for the O or S atom). For isobasic leaving groups it was found that thiolacetates are between 1 and 2 orders of magnitude less susceptible to hydroxide ion attack than are oxygen acetates …”

Structural and Mechanistic Studies on Carboxymethylproline Synthase (CarB), a Unique Member of the Crotonase Superfamily Catalyzing the First Step in Carbapenem Biosynthesis

“…Providing the pK a of the carbon ␣ to the carbonyl is low enough, hydrolysis of thioesters via an elimination-addition mechanism probably involving a ketene intermediate can occur (49). Thus, the hydrolysis of acetoacetyl-CoA, but not AcCoA (50), which has a much higher pK a , can proceed via an elimination-addition mechanism. Given the propensity of the crotonase superfamily to form enolates a ketene intermediate for the hydrolysis of the CMP-CoA cannot be ruled out.…”

Dissection of Nucleophilic and General Base Roles for the Reaction of Phosphate with p-Nitrophenyl Thiolacetate, p-Nitrophenyl Thiolformate, and Phenyl Thiolacetate

“…(a) Materials and General Methods. p -Nitrophenyl thiolacetate ( 3b ), phenyl thiolacetate ( 4b ), and p -nitrophenyl acetate ( 3a ) 4b, were prepared according to the literature procedures. Phenyl acetate ( 4a ) (Aldrich) was used as supplied.…”