Abstract
Three cocrystals of pyrazinamide (PYZ) with 2,4-dihydroxy benzoic acid (2,4HBA-PYZ), 2,6-dihydroxybenzoic acid (2,6HBA-PYZ) and 3,5-dihydroxybenzoic acid (3,5HBA-PYZ) are investigated by computational simulations. DFT calculations have been performed in order to understand the reactive properties of molecules that constitute the cocrystals. These calculations were followed by symmetry-adapted perturbation theory (SAPT) simulations to understand the interactions between molecules of the studied cocrystals. Molecular Dynamics (MD) simulations helped us to identify possible excipient substances. The ring vibrational modes have small variations during the cocrystal formation, while changes were observed in the peaks of the associated functional groups. Most reactive sites are identified by MEP maps. From the DFT analysis, we found that N–H⋯N intra molecular hydrogen between the N atom of pyrazine and H–N of amide produces conformational rigidity in the pyrazine ring in the co-crystal assembly of 2,4HBA-PYZ and 2,6HBA-PYZ but not for 3,5HBA-PYZ. The polarization nature of the functional groups was predicted by VCD spectra. Molecular docking results imply that the cocrystals might exhibit inhibitory activity against mycobacterium tuberculosis type II and against methylenetetrahydrofolate reductase and can be formulated as new anti-TB drug. The system showed fairly good light harvesting efficiency (LHE); hence, could be used in photovoltaic systems for energy conversion. Among the three cocrystal systems 2,4HBA-PYZ is a better candidate to be used in DSSC’s.
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•DFT analysis of cocrystals of pyrazinamide with hydroxybenzoic acids were reported.•Most reactive sites are identified.•Studied NLO properties, MEP and NBO.•Molecular docking studies have been discussed.