Molecular docking, spectroscopic, and quantum chemical studies on aromatic heterocycle tetrakis(4-pyridyl)cyclobutane regioisomers: potential membrane-permeable inhibitors.

Aromatic heterocyclic compounds are commonly used in pharmaceutical and agrochemical products. The usage has been also extended in the production of corrosion inhibitors and electronic, opto-electronic, and NLO devices. The four regioisomers of the aromatic heterocyclic molecule, tetrakis(4-pyridyl)cyclobutane (tpcb), were optimized, and their chemical, electronic, and biological properties were examined. The rctt and rtct isomers were isolated and further characterized by the infrared and Raman spectroscopic techniques, and their vibrational modes with attention on important functional groups were discussed. The theoretical vibrational data obtained by DFT/B3LYP/6-311++G(d,p) were in very good agreement with the experimental ones. The occupancy, bond polarization, hybridization of the N-C bond, bonding characteristics between the pyridyl carbon and cyclobutane moiety, and distribution of electron density for the four tpcb isomers have been explored through NBO analysis. The inversion barrier of the cyclobutane moiety was obtained based on the optimized structures of the planar and puckered configurations of the isomers. The rccc isomer exhibited the least electrophilic character compared to the other tpcb isomers. The chemical significance of tpcb has been further explained by the wave function analyses. Molecular docking results revealed that the tpcb ligand would possess a potential anti-viral and anti-bacterial activity via a membrane-permeable mechanism.