Investigating the Reactivity of Organophosphates with Alpha Nucleophiles: Unraveling the Mechanism and Energetics of Paraoxon Dephosphorylation by Hydroxylamine

• Grant number: 24/22658-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2025
• End date: December 31, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
• Principal Investigator: Marcela de Freitas Lima
• Grantee: Bruno Napolitano Mamede
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

The intensive use of organophosphate pesticides has triggered a global crisis due to their harmful effects on the environment and human health. One example is paraoxon (POX). This project investigates the dephosphorylation mechanisms of POX by hydroxylamine, an efficient nucleophile in cleaving O¿P bonds. In addition to the well-established anti-SN2(P) mechanism reported in the literature, alternative pathways will be explored, such as frontal attack and the SNAr mechanism, where the aromatic ring directly interacts with hydroxylamine. The research combines kinetic experiments and computational modeling based on Density Functional Theory (DFT). Experimentally, the reaction will be monitored under varying conditions (pH, temperature, and reagent concentrations), allowing the determination of kinetic parameters. Computationally, DFT calculations with functionals such as B3LYP, X3LYP, and ¿B97X-D will model transition states and intermediates. Natural Bond Orbital (NBO) analyses will also be conducted to detail the electronic aspects of the SNAr mechanism, using the JANPA software. By combining experimental and computational results, this research aims to provide a comprehensive understanding of the dephosphorylation mechanism of paraoxon by hydroxylamine, with a particular focus on the high stability of the O¿P bond.