[Interaction of various dithio- and thiophosphates containing amino acid fragments with carboxylesterase from rat liver].

The interaction of insecto-acaricides of the general formula (EtO)2P(S)SCH2CONH(CH2)nCH(R1)COOR2 and their activation metabolites (P = O analog) and detoxication products (R2 = H) with rat liver carboxylesterase was studied. The beta-alanine derivative (n = 1, R1 = H, R2 = Et) was rapidly hydrolyzed by carboxylesterase. The valine derivative (n = 0, R1 = H, R2 = Et) was hydrolytically stable, due to steric hindrances imposed by the isopropyl group, and proved to be a reversible competitive inhibitor of carboxylesterase. The corresponding monothiophosphates were not hydrolyzed by carboxylesterase, but inhibited it irreversibly. It was found that monothiophosphate derivatives of R- and S-valine irreversibly inhibit carboxylesterase, R-enantiomer being somewhat more active than S-antipode. On the other hand, under the conditions of reversible inhibition by the corresponding dithiophosphates, S-enantiomer was more active. Using model compounds, (R)- and (S)-N-chloroacetyl valine ethyl esters, it was shown that both on irreversible and reversible inhibition the differences in stereospecificity can be attributed to changes in the inhibitor orientation in the enzyme active site.