Density functional theory computational study on solvent effect, molecular conformations, energies and intramolecular hydrogen bond strength in different possible nano-conformers of acetaminophen

The molecular modeling analysis via density functional theory has been performed on all possible conformers of acetaminophen. Computations performed at B3LYP/6-311 ++G(d,p) level using the Gaussian 09 program package. The polarizable continuum model method was used to investigate solvent effects on the electronic and structure properties. The optimized structures, total energies, energy gap, chemical potential, global hardness, softness, global electrophilicity and dipole moments were calculated. From 4 different obtained conformers, A1 is the most stable one with intramolecular C-H ⋯ O hydrogen bonding. The investigated structures contain intramolecular hydrogen bonded (HB) ring which was analyzed in detail by topological parameters in terms of electron density (ρ) and its Laplacian (∇2ρBCP) at the bond critical points and ring critical points from Bather's atom in molecular quantum theory. These parameters could be treated as measure of HB strength. Results show that the C-H ⋯ O and C-H ⋯ C bonds possess low ρ and non-covalent character (∇2ρBCP > 0) whereas C-H and C-O have covalent character (∇2ρBCP < 0). The energy of HB for the most stable conformer was − 16.11 kJ/mol. Charge density distributions and chemical reactive sites of studied conformers have been obtained by molecular electrostatic potential surface.