Effects of Chemical Reactivity on the Toxicity of Phosphorus Fluoridates

Abstract

Semiempirical quantum calculations were performed on a series of organophosphorus fluoridates to determine the relative reactivity for hydrolysis. This value was determined by subtracting the energy of the metastable intermediate from the energy of the stable molecule. Plotting this relative reactivity for each compound vs. its toxicity resulted in a parabolic curve with nerve agents and other similarly toxic compounds in the center. The more reactive phosphinates and less reactive phosphates were at the edges of the graph in the region of lower toxicity. The results indicate that for compounds meeting minimal structural requirements, chemical reactivity is the principal determinant of cholinesterase inhibition.

Key Words:

• Phosphorus
• toxicity
• cholinesterase
• computational chemistry
• semiempirical
• reactivity