Bimolecular Reaction Constants Research Articles

Dissociation and phosphorylation constants for the inhibition of acetylcholinesterase by a series of novel O-ethyl O-phenyl S-n-propyl phosphorothioates

The phosphorylation, dissociation, and bimolecular reaction constants were determined for several members of a series of substituted O-ethyl O-phenyl S-n-propyl phosphorothioates in the presence of substrate. The data obtained are discussed in relation to electronegativity of substituents and in vivo toxicity.

Inhibition of flyhead acetylcholinesterase by dimethoxon analogs

The inhibition of purified housefly-head acetylcholinesterase by 16 dimethoxon analogs was studied and the phosphorylation and affinity constants determined. Except for compound XV, all the analogs were better inhibitors of flyhead acetylcholinesterase than of bovine erythrocyte acetylcholinesterase. The large bimolecular reaction constants were the result of higher affinity and phosphorylation rates. Mono-substitution on the carbamoyl nitrogen primarily affected reactivity ( k 2), whereas di-substitution affected affinity ( K a ). Modification of the 0, 0-dialkyl moiety had little effect on affinity although reactivity decreased proportionately with chain length. There is some indication that the interaction of these inhibitors with flyhead AChE is due to a considerable electrostatic contribution. The difference between target enzymes (housefly versus erythrocyte AChE) accounts in part for the selectivity of dimethoate and its analogs.

Stopped-flow studies of the inhibition of acetylcholinesterase by organophosphates in the presence of substrate

The stopped-flow technique has been applied to the determination of dissociation, phosphorylation, and bimolecular reaction constants for the inhibition of acetylcholinesterase by a potent organophosphate in the presence of a chromogenic substrate. The advantages of the method for inhibition studies are compared with those of an earlier spectrophotometric technique.

Insensitivity of acetylcholinesterase as a factor in resistance of houseflies to the organophosphate Rabon

Acetylcholinesterase from an organophosphate-resistant strain of housefly exhibited a decrease in sensitivity to Rabon in vitro, to the extent of 206-fold for the soluble enzyme and 38-fold for the particulate. These effects upon the bimolecular reaction constant, k i , were due to a 573-fold decrease in affinity of the inhibitor for the soluble and 103-fold for the particulate enzyme, coupled with a small increase in reactivity.

In vitro inhibition of acetylcholinesterase by O,O-dimethyl S-aryl phosphorothioates

In vitro inhibition of house cricket head, house fly head, and bovine erythrocyte acetylcholinesterase by O,O-dimethyl S-aryl phosphorothioates was studied by Main's kinetic treatment. The potency of the compounds as reflected by the bimolecular reaction constants ( k i ) indicated that house fly head acetylcholinesterase was the most sensitive to the inhibition followed by house cricket head and bovine erythrocyte acetylcholinesterase. There are no linear relationships between the phosphorylation rate constants and the total binding energies for the inhibition of three enzymes by this series of compounds, suggesting that the initial binding and the phosphorylation rate are not related. The structure and activity relationships were analyzed by multiple regression analyses with the use of Hammett's sigma, alkaline hydrolysis rates of the compounds, and p i constants. The hydrophobic bonding of the compound on the enzyme surface as reflected by the p i constant played a significant role in the determination of the potency of the inhibition of house cricket head and house fly head acetylcholinesterase by those compounds. However, the alkaline hydrolysis rates of the compounds, or the Hammett's sigma values seems to play a more important role in the determination of the inhibition of bovine erythrocyte acetylcholinesterase. Moderate insecticidal activity toward house crickets, house flies, and mosquito larvae were found.