Crystal structure, Hirshfeld surface analysis, DFT and mol­ecular docking studies of 4′-(benz­yloxy)-[1,1′-biphen­yl]-3-carb­oxy­lic acid

Abstract

The title mol­ecule was studied by single-crystal X-ray analysis to determine its mol­ecular structure and investigate the inter­actions present. Theoretical (obtained by DFT) and experimental parameters were compared. In addition, Hirshfeld surface analysis and mol­ecular docking studies were performed for the title compound as a ligand and the SARS-Covid-2 (PDB ID:8BEC) protein, specifically the Omicron variant.

In the title compound, C₂₀H₁₆O₃, intra­molecular C— H⋯O hydrogen bonds are observed. The dihedral angles between the aromatic benzoic acid ring and the two adjacent aromatic rings are 26.09 (4) and 69.93 (8)°, while the dihedral angle between the aromatic rings connected by the C—O—C—C [torsion angle = −175.9 (2)°] link is 89.11 (3)°. In the crystal, inversion dimers linked by pairs of O—H⋯O hydrogen bonds generate R₂²(8) ring motifs. These dimers are further linked by C—H⋯π inter­actions, forming mol­ecular sheets along (010). The mol­ecular structure was optimized by density functional theory (DFT) at the B3LYP/6–311+ G(d,p) level and the bond lengths, angles and torsion angles were compared with experimental values obtained by X-ray diffraction. The HOMO and LUMO were calculated, the energy gap between them being 4.3337 eV. Further, the inter­molecular inter­actions were qu­anti­fied using Hirshfeld surface analysis and fingerprint plots and energy frameworks were generated. The two-dimensional fingerprint plots indicate that the major contributions to the crystal packing are from H⋯H (39.7%), H⋯C (39.0%) and H⋯O (18.0%) inter­actions. The energy framework calculations reveal that the dispersion energy (E_dis= 201.0 kJ mol⁻¹) dominates the other energies. Mol­ecular docking studies were carried out for the title compound as a ligand and the SARS-Covid-2 (PDB ID:8BEC) protein, specifically the Omicron variant, was used as a receptor giving a binding affinity of −7.6 kcal mol⁻¹.