Thio-Induced Organophosphate Breakdown Promoted by Methimazole: an Experimental and Theoretical Study.
Renan B CamposLucas A CapatoPatrícia M SoaresDean J TantilloElisa S OrthPublished in: ChemPlusChem (2024)
Investigating the reactivity of small nucleophilic scaffolds is a strategic approach for the design of new catalysts aiming at effective detoxification processes of organophosphorus compounds. The drug methimazole (MMZ) is an interesting candidate featuring two non-equivalent nucleophilic centers. Herein, phosphoryl transfer reactions mediated by MMZ were assessed by means of spectrophotometric kinetic studies, mass spectrometry (MS) analyses, and density functional theory (DFT) calculations using the multi-electrophilic compound O,O-diethyl 2,4-dinitrophenyl phosphate (DEDNPP). MMZ anion acts primarily as an S-nucleophile, exhibiting a nucleophilic activity comparable to that of certain oximes featuring alpha-effect. Selective nucleophilic aromatic substitution was observed, consistent with the DFT prediction of a low energy barrier. Overall, the results bring important advances regarding the mechanistic understanding of nucleophilic dephosphorylation reactions, which comprises a strategic tool for neutralizing toxic organophosphates, hence promoting chemical security.
Keyphrases
- density functional theory
- mass spectrometry
- molecular dynamics
- multiple sclerosis
- liquid chromatography
- drug induced
- diabetic rats
- ms ms
- emergency department
- molecular docking
- high glucose
- amino acid
- simultaneous determination
- ionic liquid
- capillary electrophoresis
- zika virus
- tissue engineering
- solid phase extraction