D. Wustner, T. Fukuto
Sep 1, 1974
Citations
0
Influential Citations
25
Citations
Journal
Pesticide Biochemistry and Physiology
Abstract
Abstract The synthesis of the four optical isomers of known absolute configuration of O -2-butyl S -2-(dimethylammonium)ethyl ethylphosphonothioate hydrogen oxalate is described. Values for the affinity constant ( K a ), phosphonylation constant ( k p ), and bimolecular inhibition rate constant ( k i ) for the inhibition of bovine erythrocyte acetylcholinesterase, housefly-head acetylcholinesterase, and horse serum cholinesterase by the chiral isomers and the racemic mixture are reported. Using a relatively simple spectrophotometric technique, inhibition times as low as 0.5 sec were used. The phosphorus isomers of S p configuration were more potent inhibitors than their R p enantiomers by 1630-fold against the bovine enzyme, 9120-fold against the fly-head enzyme, and 40-fold against the horse serum enzyme. The differences in anticholinesterase activity were attributable to differences in the affinity constant, K a , and the phosphonylation constant, k p . Small but consistent inhibition rate differences were attributable to asymmetry at carbon. Against horse serum cholinesterase, the S C isomers indicated the presence of three kinetic forms in this enzyme preparation.