A quantum chemical computational insight into the intramolecular hydrogen bond interaction in an antibacterial drug molecule-2-acetylindan-1,3-dione

A Density Functional Theory (DFT)-based quantum chemical computational study has been carried out to characterize the intramolecular hydrogen bonding (IMHB) interaction in a potent bio-active drug molecule viz., 2-acetylindan-1,3-dione (2-AID). The IMHB interaction has been explored by calculation of electron density ρ(r) and Laplacian ∇2ρ(r) at the Bond Critical Point (BCP) using Atoms-In-Molecule (AIM) theory. Topological features, energy densities provided by AIM theory are calculated with ρ(r) for a number of intramolecular H-bond distances. The results suggest that at equilibrium geometry the IMHB interaction in the molecule develops certain characteristics typical of covalent interaction. The role of hyperconjugative charge transfer interaction in the IMHB has been critically evaluated and addressed under the provision of Natural Bond Orbital (NBO) analysis. The study also pays proper attention to an important feature of IMHB interaction, namely the directional nature, within the NBO framework in a consensus manner. Simulated IR spectra also provide reinforcing evidence for IMHB interaction on the basis of OH stretching frequency shift. The optimized geometry features, molecular electrostatic potential (MEP) map analysis are also found to produce a consensus view in relation with the formation of IMHB in 2-AID.