A B3LYP/DFT Study on the Structure Activity Relationship for Benzimidazole Derivatives in Water Solution

Abstract

Abstract: In this article, a theoretical chemical study on 41 benzimidazole derivatives compounds used to treat osteoporosis was performed in water phase using density functional theory (DFT) based on the 6-311 basis set and B3LYP method as the level of theory to calculate energetic behavior and quantitative chemical descriptors such as energy gap between HOMO and LUMO, the total energy of different orbital transitions, chemical hardness, softness, electrophilicity index, and electronegativity. The results showed a noticeable difference between the compounds concerning chemical parameters due to substituting the active chemical molecules at the compounds’ R1, R2, R3, and R4 sites. The results showed that compound no. 3 could be considered the most exciting compound due to its unique values obtained. On the other hand, it was found an appropriate relationship between the quantitative arithmetic variables and the IC50 values for each compound. Statistical analysis between the compounds under test and a quantitative descriptor of the ten traits were included to produce two different prediction models based on artificial neural networks due to negative and positive IC50 values after data pre-processing.