Abstract
This work presents the quantum chemical calculations of the monomer and dimer of benznidazole using density functional theory (DFT) at the B3LYP/6-311++G(d,2p) level of theory. A one-dimensional potential energy surface scan was carried out across flexible bonds to find the minimum energy structure. The structure with minimum energy was taken as a monomer and dimer is constructed based on intermolecular hydrogen bonding N-H…O. The vibrational analysis was conducted by comparing the calculated FT-IR and FT-Raman spectra of the monomer and dimer with the experimental ones. The red shift in the spectra of amide and carbonyl functional groups indicates their involvement in intermolecular hydrogen bonding in crystal packing, while the other peaks showed good agreement with the experimental result. The intra- and intermolecular interactions in the monomer and dimer were analyzed using various tools. The steric effects and van der Waals forces in the dimer were found to be more effective than the monomer. The dimer in the gaseous medium was found to have a lower Frontier molecular orbital energy (ΔE(L-H)) value than the monomer, suggesting that it is more reactive in a gaseous medium. The ELF value for hydrogen in monomer and dimer around the ring was found to be more which confirms that the electrons in these regions are more localized. The negative value of the overlap population density of states (OPDOS) both in monomer and dimer indicate that there are anti-bonding orbitals between the acetamide and the benzyl groups of the compound. The drug potential of benznidazole was evaluated by molecular docking with carbonic anhydrase XII, which shows the highest binding affinity of (-8.3 kcal/mol) with 6YH8, indicating that benznidazole is its potent inhibitor.