Conformation Analysis and Self-Consistent Field Energy of Immune Response Modifier, 1-(2-methylpropyl)-1H-imidazo[4, 5]quinolin-4-amine (Imiquimod)

Abstract

1-(2-methylpropyl)-1H-imidazo[4, 5]quinolin-4-amine (imiquimod) is an immune response modifier and is used to treat genital warts, superficial basal cell carcinoma, and actinic keratosis. Conformational analysis and geometry optimization of imiquimiod was performed according to the Hartree-Fock (HF) calculation method by Argus Lab 4.0.1 software. Molecular mechanics calculations were based on specific interactions within the molecule. These interactions included stretching or compressing of bond beyond their equilibrium lengths and angles, torsional effects of twisting about single bonds, the Van der Waals attractions or repulsions of atoms that came close together, and the electrostatic interactions between partial charges in imiquimod due to polar bonds. The steric energy for imiquimiod was calculated to be 59.09 kcal/mol. It was concluded that the lowest energy and most stable conformation of imiquimiod was 59.09 kcal/mol. The most energetically favourable conformation of imiquimiod was found to have a heat of formation of 908.38 kcal/mol. The self-consistent field (SCF) energy was calculated by geometry convergence function using Argus Lab software. The most feasible position for the drug to interact with the receptor was found to be-95.99 au (−60240.26 kcal/mol).