pH-Dependent mechanistic variations in the hydrolysis of Sarin: when is water self-catalysis required?

Mechanistic variations in the hydrolysis of Sarin were investigated using density functional theory under acidic, neutral and alkaline conditions. The most favorable pathway for alkaline hydrolysis is consistent with nucleophilic attack of hydroxide on the phosphorus atom opposite to the P-F bond. Neutral hydrolysis requires a self-catalyzed attack of water involving an asynchronous (late) protonation of the PO group concerted with the nucleophilic attack. In contrast, a single water molecule is sufficient to promote Sarin hydrolysis under acidic conditions due to the key role of the hydronium ion, which acts in a specific orientation without interacting with the PO group.