Mathematical and Physical SciencesOrganophosphorus (OP) nerve agents are a class of toxic compounds that inhibit acetylcholinesterase (AChE), an enzyme that catalyzes the conversion of acetylcholine to choline at neurosynaptic junctions. OP inhibits AChE by binding to the active site and this undergoes a subsequent irreversible process called aging, where the OP-AChE adduct is dealkylated. This results in the accumulation of excess acetylcholine in the central nervous system that causes significant nerve damage. Current oxime-based pharmaceutical agents, such as 2-PAM, used to treat inhibited AChE are ineffective on aged AChE. Previous studies have shown that quinone methides (QM) are alkylating agents and these could potentially reverse the aging process through a kinetically favored realkylation mechanism. In the past, we have designed and synthesized a library of QM precursors. Our research focuses on the analysis of these alkylating compounds and investigating their ability to realkylate model phosphonate.National Institute of Health (NIH) Grant 1U01–NS087983Academic Major: Chemistr
