Computational chemistry study of toxicity of some m -tolyl acetate derivatives insecticides and molecular design of structurally related products.

Molecular descriptors (including quantum chemical, topological and physicochemical descriptors) were calculated for five m -tolyl derivatives insecticides [namely, carbosulfan (CBS), carbofuran (CBF), isoprocab (IFP), methiocarb (MTC) and isocarbophos (ICP)]. Calculated quantum chemical parameters included the total energy, the electronic energy, the binding energy, the core-core repulsion energy, the heat of formation, the dipole moment and the frontier molecular orbital energies. All the calculated quantum chemical parameters (except dipole moment) exhibited strong correlation with the experimental LD50 values of the studied insecticides (at various Hamiltonians). Calculated topological parameters included the molecular topological index (MTI), polar surface area (PSA), total connectivity (TC), total valence connectivity (TVC), Wiener index (WI), topological diameter (TD) and Balaban index (BI). However, only MTI, PSA, WI and BI exhibited excellent correlation with the toxicological activity of the insecticides. Also among all the calculated physicochemical parameters [logP, surface area (SA), surface volume (SV), hydration energy (EHydr ), polarizability (PLZ) and refractivity (RFT)], only SV, EHydr , PLZ and RFT were useful in establishing quantitative structure activity relationship (QSAR). Application of QSAR indicated that the calculated theoretical LD50 values for the studied insecticides displayed excellent correlation with experimentally derived LD50 values. However, best results were obtained from quantum chemical descriptors under modified neglect of atomic overlap (MNDO). The toxicity profile of the insecticides also correlated strongly with ionization energy, electron affinity, global softness and global harness. Reactive sites of each of the insecticides were established using Fukui function, Huckel charges and HOMO/LUMO diagrams. Six new molecules were proposed and their theoretical activities were estimated. The proposed molecules included 2-methyl-2-(methylthio)-2,3-dihydrobenzofuran-7-yl methylcarbamate, O -methyl O -2-((methylaminooxy)carbonyl)phenyl phosphoramidothioate, 2-((methylaminooxy)carbonyl)phenyl methylcarbamate, 2-(1-(methylthio)ethyl)phenyl methylcarbamate, N -methyl- O -(2-(methylthiooxy) benzoyl) hydroxyl amine and 4-methyl naphthalen-2-yl methylcarbamate. Some of the proposed molecules exhibited negative values of LD50 (indicating extreme toxicity) while two of them exhibited values that are comparable to existing insecticides.