Computational investigation of solvent interaction (TD-DFT, MEP, HOMO-LUMO), wavefunction studies and molecular docking studies of 3-(1-(3-(5-((1-methylpiperidin-4-yl)methoxy)pyrimidin-2-yl)benzyl)-6-oxo-1,6-dihydropyridazin-3-yl)benzonitrile

Abstract

Initially, we have done the conformational analysis, total of 564 confirmations were available, we noted highest energy value is 56.499 and the ring energy is 67.982. After getting conformational analysis results, we choose the highest energy value structure, that structure is only used for further DFT calculations. The B3LYP/cc-pVDZ basis set was used to optimize the best results for the 3-(1-(3-(5-((1-methyl piperidin-4-yl) methoxy)pyrimidin-2-yl) benzyl)-6-oxo-1,6 -dihydropyridazin -3-yl)benzonitrile (CD). The NBO analysis confirms the highest stabilization energy 39.53 kcal/mol, from bonding LP (1) - N22 to anti-bonding π*(N21 - C24). The ELF, LOL, ALIE, and RDG, analysis was done by using Multiwfn software and confirmed the localization and delocalization of electrons. The thermodynamic properties and electron density were calculated with the help of Gaussian-16w software. Analyses of NLO parameters, MEP, UV-vis, and HOMO-LUMO were performed using five different solvents (chloroform, water, acetonitrile, ethanol, and DMSO). The docking study was done using Autodock software, and we identify the protein-ligand interaction, the best binding score is -5.69 kcal/mol.

Keywords

• Computational (DFT)
• Solvents effect
• Docking
• Topological analysis
• NBO