Cocrystals of pyrazinamide with p-toluenesulfonic and ferulic acids: DFT investigations and molecular docking studies

Abstract Cocrystals of pyrazinamide with p -toluenesulfonic acid (PZTSA) and ferulic acid (PZFER) are investigated by density functional calculations to find geometrical parameters, wavenumbers and different molecular properties. The vibrational modes associated with the phenyl and pyrazine rings have small changes during the cocrystal formation, while changes are associated with the amide group of pyrazinamide, hydroxyl and carboxylic groups of ferulic acid and SO 3 group of PZTSA. Using density functional theory method the molecular geometries of the co-crystals were optimized in the ground state and a comparison is made with the reported experimental data. The theoretically obtained wavenumbers are assigned by means of potential energy distribution. The downshift of different modes in the infrared spectrum is due to hydrogen bonding and this is supported by the strong hyper conjugative interactions given by natural bond orbital analysis. HOMO is delocalized over the entire molecule except phenyl ring and methyl group and LUMO is delocalized over the entire molecule except C ONH 2 group for PZTSA while for PZFER, HOMO and LUMO are delocalized over the ferulic acid. From the MEP plot, electron rich regions are mainly localized over C O and SO 3 groups of PZTSA while for PZFER, all the oxygen atoms electron rich regions. The first hyperpolarizability of PZTSA and PZFER are 5.99 and 89.66 times that of urea. Different molecular properties like, global chemical descriptors, frontier molecular orbital analysis, nonlinear optical properties and natural bond orbital analysis are also discussed in the present work. The different functional groups in the title compounds are identified by configurations markers using the theoretical VCD spectra analysis. Light harvesting efficiency analysis shows that PZFER is suitable for photo sensitizers in DSSC's. Docking results suggest that the compounds might exhibit inhibitory activity against mycobacterium tuberculosis type II and the compounds can be developed as a new anti -TB drug.