Conformational stability, spectroscopic signatures and biological interactions of proton pump inhibitor drug lansoprazole based on structural motifs

Abstract

Structure based biological and chemical properties of Lansoprazole (LSP) have been studied by spectroscopic and quantum chemical methods. The geometrical parameters of the title compound obtained by DFT calculation are compared with single crystal XRD data. The conformational flexibility of the title compound has been discussed on the basis of the potential energy profile achieved from the rotation of various groups present in the molecule and the minimum energy conformer has been determined. The spectroscopic fingerprints are studied by variety of experiments (IR, Raman, UV, and NMR). Normal mode analysis is performed to assign the vibrational frequencies according to the potential energy distribution (PED). Simulation of infrared and Raman spectra has led to an excellent overall agreement with the observed spectral patterns by refinement of scale factors. TD-DFT approach is used to investigate the excited states of molecule and prediction of electronic absorption spectra. The ¹H nuclear magnetic resonance (NMR) chemical shifts of the molecule are calculated by the gauge independent atomic orbital (GIAO) method and compared with experimental results. Prediction of Activity Spectra analysis (PASS) of the title compound has been done to explore several biological and toxic effects with high probability. The lipophilicity and aqueous solubility have been calculated to get insight into cell membrane penetration and drug absorption processes in biological systems. The molecular docking is performed to identify the binding energy of the ligand with the active site of protein. These studies show that several sites in the molecule are crucial for bonding and these results lead us to the conclusion that the compound might be metabolized by human protein. Electron density-based local reactivity descriptors such as Fukui functions have been calculated to describe the chemical reactivity sites within the molecule.