Monoalkyl sulfates as alkylating agents in water, alkylsulfatase rate enhancements, and the “energy-rich” nature of sulfate half-esters

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Abstract
Alkyl sulfate monoesters are involved in cell signaling and structure. Alkyl sulfates are also present in many commercial detergents. Here, we show that monomethyl sulfate acts as an efficient alkylating agent in water, reacting spontaneously with oxygen nucleophiles >100-fold more rapidly than do alkylsulfonium ions, the usual methyl donors in living organisms. These reactions of methyl sulfate, which are much more rapid than its hydrolysis, are insensitive to the nature of the attacking nucleophile, with a Brønsted β nuc value of −0.01. Experiments at elevated temperatures indicate a rate constant of 2 × 10 −11 s −1 for the uncatalyzed hydrolysis of methyl sulfate at 25°C ( t 1/2 = 1,100 y), corresponding to a rate enhancement of ≈10 11 -fold by a human alkylsulfatase. Equilibria of formation of methyl sulfate from methanol and sodium hydrogen sulfate indicate a group transfer potential (Δ G′ pH7 ) of −8.9 kcal/mol for sulfate ester hydrolysis. The magnitude of that value, involving release of the strong acid HSO 4 − , helps to explain the need for harnessing the free energy of hydrolysis of two ATP molecules in activating sulfate for the biosynthesis of sulfate monoesters. The “energy-rich” nature of monoalkyl sulfate esters, coupled with their marked resistance to hydrolysis, renders them capable of acting as sulfating or alkylating agents under relatively mild conditions. These findings raise the possibility that, under appropriate circumstances, alkyl groups may undergo transfer from alkyl sulfate monoesters to biological target molecules.

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