Possible role of Mg2+ ion in the reaction of organophosphate (dichlorvos) with serine

Organophosphate pesticides (OPs) inhibit both true and pseudo-cholinesterases by reaction with the hydroxyl group of serine in their active sites. Poisoning with OPs is commonly seen in clinics. A common antidote for OP poisoning is atropine but, after ageing and OP dealkylation, even oximes could not be effective. It has been shown that oximes are not always useful in management of OP poisoning. On the other hand, magnesium has been found effective in both clinical and experimental studies. Studies to find more effective antidotes for OP poisoning are in progress. Presently, the possible role of magnesium ion in catalysis of reaction of dichlorvos (2,2-dichlorovinyl dimethyl phosphate, DDVP), a water-soluble OP, with serine is proposed. The hydroxyl group of serine could be a target to which DDVP can react. Nucleophilic attack of pralidoxime to DDVP was previously investigated. To confirm the idea, data were derived from recent and previous research on the role of magnesium in phosphoryl group transfer reactions. Possible reactions of serine and pralidoxime with DDVP in the absence and the presence of magnesium ion were separately investigated theoretically.We propose that the chemical reaction of serine with DDVP exclusively occurs in the presence of a magnesium divalent cation, whereas the reaction of pralidoxime with DDVP occurs independent of the presence of the magnesium ion. The role of the dissociation constant (pKa) of functional groups in these reactions seems important.It is suggested that application of serine in combination with the magnesium cation can become a more efficient antidote for treatment of OP poisoning.

Figure optionsDownload as PowerPoint slideHighlights▸Proposed mechanism for catalytic role of magnesium ion in nucleophic attack of serine to DDVP. ▸Magnesium reduces the pKa of serine hydroxyl group and favors the reaction of serine with DDVP. ▸It is proposed that magnesium acts through a ion radical mechanism.