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In a continuing effort for our research group, we identify new active 1,2,4-triazine derivatives as novel cancer preventive agents that target CYP1A1 activity, through the application of quantitative structure–activity relationship (QSAR) theory. For this purpose, novel fused 1,2,4-triazine derivatives, namely, 4-Amino-6-substituted benzyl-3-(2-substituted benzylidenehydrazinyl)-1,2,4-triazin-5(4H)-ones and acetylated 6-substituted benzyl-7-oxo-3-substituted phenyl-2,3-dihydro-7[Formula: see text]-[1,2,4]triazolo[4,3-[Formula: see text]][1,2,4]triazine analogs were utilized for the prediction of the QSAR model. Furthermore, the application of this QSAR equation served successfully as a rational guide for predicting the activities of newly synthesized analogs. The DFT calculation was applied to recognize the physicochemical parameters at B3LYP/6- 311G* level to gain a clear view of global and local molecular reactivity. Besides, the molecular features of the investigated compounds were identified through HOMO, LUMO and molecular electrostatic potential (MEP) which were plotted to determine the charge transfer within the molecules. Promising two novel 1,2,4-triazine compounds were identified with observed significant inhibitions (83% and 67%) and CYP1A1 activity was predicted. The chemical configuration of the two actives showed good alignment of [Formula: see text]-methoxy benzyl aminotriazinone fragments, hydrazino and carbonyl linker in structure–activity relationship and interaction. Molecular modeling analysis supported with MD simulations was undertaken to investigate different binding interactions with the target binding site. These projects offered a good application of a promising QSAR model for prediction of highly active compounds for further lead optimization.

The imidazolium ion is a typical species that is used for providing the cation part in the organic ionic liquid. The DFT calculations on the interaction between dibromomethylimidazolium cation and trihalomethane sulfonates, CX3SO3-where X = F, Cl, Br and H, have been performed. The intermolecular interactions which usually control the properties of these organic liquids were investigated based on DFT calculations. It was found that intramolecular interaction is most favored when X is equal to H. These interactions in the complex units were found to depend on the electrostatic force between the positively charged Br-atoms in the dibromomethylimidazolium and the free O2-atom in the CX3SO3 -ion. The overlap between the HOMO of the CX3SO3 -as electron-rich Lewis base and the empty LUMO of the dibromomethylimidazolium cation indicates that these interactions are orbitally controlled.

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