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

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 ␤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 Ϸ10 11 -fold by a human alkylsulfatase. Equilibria of formation of methyl sulfate from methanol and sodium hydrogen sulfate indicate a group transfer potential (⌬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.group transfer potential ͉ methyl transfer ͉ sulfate monoester D imethyl sulfate and other diesters of sulfuric acid are powerful alkylating agents, widely used in organic synthesis and chemically induced mutagenesis. Monoalkyl sulfates, in contrast, undergo spontaneous hydrolysis only at high temperatures (1) and appear never to have been shown to act as alkylating agents under any conditions. Many commercial detergents, formulated on the basis of that presumed lack of reactivity, incorporate SDS, also known as sodium lauryl sulfate, as their active ingredient. In living organisms, O-sulfated lipids and polysaccharides, produced through the intermediacy of 3Ј-phosphoadenosine 5Ј-phosphosulfate, are involved in maintaining cell structure. Sulfate monoesters also play a central role in recently discovered signaling functions that are sensitive to variations in their detailed structures (for recent reviews, see refs. 2 and 3).The identification of roles for sulfuric acid monoesters in biological signaling and structure has aroused increasing interest in the chemical properties of these negatively charged molecules, and of the enzymes responsible for their biosynthesis and degradation. To appreciate the effectiveness of any enzyme as a catalyst, it is of interest to compare the rate of an enzyme reaction with the rate of a reaction proceeding in water in the absence of a catalyst. Recent work has shown that hydrolases that act on phosphate monoesters produce rate enhancements...

How anion and cation species influence the tribology of a green lubricant based on ionic liquids

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No oxygen isotope exchange between water and APS–sulfate at surface temperature: Evidence from quantum chemical modeling and triple-oxygen isotope experiments

“…Activation energies of corresponding reactions are calculated directly and used as theoretical determinants for the possibility of corresponding exchange channels. Hydrolysis of sulfate and phosphate esters also play a central role in a variety of biochemical processes and modeling such systems is feasible (Rodiguez-Lopez et al, 2001;Akola and Jones, 2003;Wolfenden and Yuan, 2007, and references cited therein). Independently, we examine our model results on the potential for APS-sulfate-water oxygen exchange using in vitro experiments that utilize triple-oxygen-isotope labeled solutions.…”

Thermodynamics and kinetics of the hydrolysis of atmospherically relevant organonitrates and organosulfates

“…As the equilibrium constant K is the actual experimental property measured, a linear regression analysis of lnK vs. 1/T was performed to yield the thermodynamic parameters H hyd and −T S hyd . The monofunctional primary organosulfate hydrolysis thermodynamics parameters were previously reported for the methyl (Wolfenden and Yuan, 2007), the ethyl (Clark and Williams, 1957) and the 1-butyl (Minerath et al, 2008) systems (which were measured at varying sulfuric acid and water activities) were reanalyzed in terms of this standard definition of the equilibrium constant, and the thermodynamic parameters for these systems are reported in Table 1. The thermodynamic parameters obtained for the difunctional primary or secondary butyl organosulfate systems in the present work are reported in Table 2.…”