A comparative study for molecular insight on riparins (I–III) by quantum chemical, spectroscopic, and molecular docking methods

Abstract

This work presented the conformer analysis of riparins (I-III) through a one-dimensional potential energy scan and investigated the most stable conformer. This study aims to provide molecular insight into the most stable structure of riparins (I-III) using density functional theory calculations at the B3LYP/6-311++G(d,p) level of theory. The calculated FT-IR, Raman, and UV–Vis absorption spectra showed agreement with the experimental results after comparison. In riparin I, the N–H and C=O groups’ experimental wavenumber red shifted in comparison to the computed value, suggesting that they participate in intermolecular hydrogen bonding for crystal packing. The C=O and O–H groups in riparin II establish an intramolecular hydrogen bond, whereas both O–H groups in riparin III contribute to intramolecular hydrogen bonding with the C=O and N–H groups, which results in alterations in wavenumbers. This conclusion was supported by quantum theory of atoms in molecule, reduced density gradient plot, and electrostatic potential surface analysis. For riparins I, II, and III, the frontier molecular orbital energy gap (${\Delta E}_{L-H}$) was determined to be 4.925, 4.817, and 4.729 eV, respectively. This suggests that riparin I is more kinetically stable and riparin III is more reactive. ADMET analysis predicts the absorbance of riparin III in the gastrointestinal tract, while riparins I and II penetrate the blood–brain barrier. Molecular docking of riparins (I–III) with PDB: 1QR2 and 2QR2 reveals that riparin III has the highest binding affinity (−8.6 kcal/mol) with 1QR2, suggesting it a potent inhibitor of 1QR2.