A quantum chemical study of molecular properties and QSPR modeling of oximes, amidoximes and hydroxamic acids with nucleophilic activity against toxic organophosphorus agents

作者：Alencar Filho Edilson B; Santos Aline A; Oliveira Boaz G

来源：Journal of Molecular Structure, 2017, 1133: 338-347.

DOI：10.1016/j.molstruc.2016.12.035

• alpha-nucleophiles
• Organophosphorus poisoning
• Intramolecular hydrogen bond
• B3LYP
• QTAIM
• QSPR

The proposal of this work includes the use of quantum chemical methods and cheminformatics strategies in order to understand the structural profile and reactivity of alpha-nucleophiles compounds such as oximes, amidoximes and hydroxamic acids, related to hydrolysis rate of organophosphates. Theoretical conformational study of 41 compounds were carried out through the PM3 semiempirical Hamiltonian, followed by the geometry optimization at the B3LYP/6-31+G(d,p) level of theory, complemented by Polarized Continuum Model (PCM) to simulate the aqueous environment. In line with the experimental hypothesis about hydrolytic power, the strength of the Intramolecular Hydrogen Bonds (IHBs) at light of the Bader's Quantum Theory of Atoms in Molecules (QTAIM) is related to the preferential conformations of alpha-nucleophiles. A set of E-Dragon descriptors (1,666) were submitted to a variable selection through Ordered Predictor Selection (OPS) algorithm. Five descriptors, including atomic charges obtained from the Natural Bond Orbitals (NBO) protocol jointly with a fragment index associated to the presence/absence of IHBs, provided a Quantitative Structure-Property Relationship (QSPR) model via Multiple Linear Regression (MLR). This model showed good validation parameters (R-2 = 0.80, Q(loo)(2) = 0.67 and Q(ext)(2) = 0.81) and allowed the identification of significant physicochemical features on the molecular scaffold in order to design compounds potentially more active against organophosphorus poisoning.

• 出版日期2017-4-5