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In this communication, we report the first determination of 34S kinetic isotope effects (KIEs) for the hydrolysis of sulfate monoesters. The method involves the conversion of the inorganic sulfate, acquired at partial extent of reaction, to SO2, followed by isotope ratio determination by mass spectrometry. The KIEs determined for p-nitrophenyl sulfate and p-acetylphenyl sulfate are 1.0154 (+/-0.0002) and 1.0172 (+/-0.0003), respectively. These results, together with previous peripheral 18O KIE values, are inconsistent with an associative mechanism. The isotope effect method we report should also prove useful for studying the mechanism of other sulfuryl group transfers, including sulfatase and sulfotransferase reactions, as well as sulfate hydrolyses under other conditions.

The first synthesis of alkyl disulfonimide oligomers is presented. In the process of synthesizing these oligomers, previously unreported reactivity of the N-substituted disulfonimide functional group was discovered. Under basic conditions, unexpected lengthening of the oligomers occurs through a "transdisulfonimidation" reaction, whereby new disulfonimides are synthesized from existing ones by reaction with sulfonamide anion. This process appears to proceed via formation of a sulfene intermediate. Support for the E1cB(Rev) mechanism includes isotope scrambling, substituent effects, and sulfene trapping.

N-Sulfonylphosphoramidates have been synthesized to investigate the electrostatic requirements for binding to alkaline phosphatase. Alkyl- and aryl N-benzylated sulfonamides were phosphorylated with bromophosphates or synthesized via phosphoramidite chemistry in moderate yields (44-77%.) The resulting tribenzylated N-sulfonylphosphoramidates may be deprotected in one step to give the free acids in quantitative yields. Physical data of N-sulfonylphosphoramidates, including pK(a)'s and stability toward hydrolysis, were determined. Inhibition data suggests that AP does not bind trianionic N-sulfonylphosphoramidates better than dianionic N-sulfonylphosphoramidates, although N-sulfonylphosphoramidates are bound tighter than N-phenylphosphoramidate. k(cat) for the hydrolysis of N-sulfonylphosphoramidates by bovine and E. coli alkaline phosphatases is 10-60% that of p-nitrophenyl phosphate.

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