Exploring the reaction mechanistic pathway for the sensing of G-Series nerve agent with Kemp's triacid derivative: A computational study

Kemp's triacid derivative have been reported as a candidate for sensing of nerve agents employing the photoinduced electron transfer (PET) processes. The sensor probe molecules were prepared with primary alcohol in very close proximity to a tertiary amine to acylate the alcohol with rapid intramolecular N-alkylation to produce quaternary ammonium salt. The reaction pathways for the formation of quaternary ammonium salt and isomethyl propyl phosphonate remain unexplored. In this report, the mechanistic pathways of G-series nerve agents sarin and its simulant diethylcholorophosphate (DCP) with Kemp's triacid derivatives has been explored computationally. The calculations performed with B3LYP-D3/6-311+G(d,p) level of theory in DCM solvent revealed that the reaction proceeds via intermolecular and intramolecular S_N2 pathways. The probe molecule is sterically hindered, therefore, the frontside and backside S_N2 reaction pathways have been examined. The computed results suggest that the first intermolecular S_N2 reaction of Kemp's triacid derivatives (I & II) with sarin for the backside attack is energetically favored compared to the frontside attack and the following intramolecular S_N2 reaction is a barrierless process. The calculations performed with simulant diethylcholorophosphate (DCP) and Kemp's triacid derivatives (I & II) show that the reactions are energetically more facile compared to the nerve agent sarin molecule. The Distortion-Interaction model and ΔNBOSteric analysis showed that the back side is energetically favored over the front side attack in such S_N2 reactions. The designed Kemp's triacid derivative (II) with phosphorus center for sensing sarin and (DCP) suggests that the size of the hetero centers are important to facilitate the reaction in the probe molecule.