QSAR Analysis of 6-chloro-N2,N4-diethyl-1,3,5-triazine-2,4-diamine Derivatives; a Theoretical Study

The remarkable inhibitory effect is reinforced by the presence of heteroatoms such as sulfur (S), oxygen (O) and nitrogen (N) [1]. Density Functional theory (DFT) has been recently used [2], to describe the interaction between the activities and molecular structures. The molecular band gap was computed as the first vertical electronic excitation energy from the ground state using the time-dependent density functional theory (TD-DFT) approach as implemented in Gaussian 03. A quantitative structure–activity relationship (QSAR) study is performed on a set of 6-chloro-N2,N4-diethyl-1,3,5-triazine-2,4-diamine derivatives to reveal structural and quantum-chemical features influencing the toxic effect. All quantum-chemical calculations are carried out at DFT/B3LYP level of theory with 6-311++G** basis set Quantum-chemical calculations have been applied for electronic properties and wave function computations. Wave functions were further analyzed, and the properties derived from the analysis of electron density were applied to model the toxicity data. The results indicate that the charge on nitrogen atom plays an important role in the toxic behavior. Electron density, as well as kinetic energy densities influence the toxic effect of 6-chloro-N2,N4-diethyl-1,3,5-triazine-2,4-diamine compounds. Also, higher values of dipole moment indicate the higher toxicity in current compound series. Among the quantum topological descriptors electron density is believed to be the most influential. This study shows that the nature of substituents has very important determining role in toxicity of these compounds. Also, it was found that molecular charge distribution and strength of the bonds play vital role in stability of compound, which is directly related to its toxicity. Obtained QSAR models are beneficial for virtual screening of toxicity for new compounds of interest. Scheme: 6-chloro-N2,N4-diethyl-1,3,5-triazine-2,4-diamine