Sulfonyl Fluorides as Inhibitors of Esterases. I. Rates of Reaction with Acetylcholinesterase, α-Chymotrypsin, and Trypsin

Abstract

The second-order rate constants for inactivation of acetylcholinesterase, α-chymotrypsin, and trypsin by a series of sulfonyl fluorides have been determined. These compounds are most reactive toward chymotrypsin, but the same order of relative reactivities holds for both chymotrypsin and trypsin: phenylmethane- > 2-phenylethane- 1- > benzene- > 2-methylpropane-1- > methanesulfonyl fluoride. This order, except for methanesulfonyl fluoride, is rationalized on the basis of steric and polar factors: the data can be fitted to the general Taft relationship. Methanesulfonyl fluoride, however, is about one-ten thousandth as reactive toward chymotrypsin as would be predicted. With acetylcholinesterase only the methane and benzene derivatives react at measurable rates, and limits are set upon the values of the rate constants for the other compounds. A hypothesis compatible with the data is that a reversible complex between the sulfonyl fluoride and enzyme forms before sulfonylation. At present, the evidence that binding markedly increases reactivity is suggestive, but not conclusive. © 1963, American Chemical Society. All rights reserved.