Investigation of the molecular basis of halogenated Schiff base derivative by combined crystallographic and computational studies.

Halogenated Schiff base derivatives are gaining more popularity in supramolecular chemistry due to the synergistic effect of hydrogen and halogen-based noncovalent interactions, which helps to design novel therapeutic materials. In this work, we have examined the nature of molecular interactions to investigate the structure-functional relationship of a halogen-based derivative. The FTIR, HRMS and NMR spectroscopic techniques confirmed the formation of the desired novel Schiff base compound. Further, crystal structure studies showed an infinite 1D supramolecular chain formed by type-I halogen…halogen interaction. The Hirshfeld surface and enrichment ratio analyses were performed to visualize and assess the role of diverse interactions involved in crystal packing. The QTAIM, NCI, LOL and ELF studies were conducted extensively to comprehend the strength of interaction constructed based on electron density distribution. The global and local reactive indices were determined using DFT studies to analyze the molecular properties of the compound. Antibacterial activity against MRSA bacteria was performed and showed a good zone of inhibition. The docking analysis was performed for 1mwt protein and validated. The in silico molecular docking studies of the halogenated Schiff base structure with the penicillin-binding protein showed a good docking affinity of -7.5 kcal/mol and supported by in vitro studies. The ligand binding stability within the protein's active site was further demonstrated by molecular dynamics (MD) simulation studies for the Schiff base molecule.Communicated by Ramaswamy H. Sarma.

Synthesis of Pyrimidine Incorporated Piperazine Derivatives and their Antimicrobial Activity.

Thiophene substituted chalcones (1a-e) were cyclised with thiourea in presence of potassium hydroxide to get 4-substituted-6-(thiophen-2-yl)pyrimidine-2-thiols (2a-e) which were then stirred with methyl iodide to obtain 4-substituted-2-(methylsulfanyl)-6-(thiophen-2-yl)pyrimidines (3a-e). Compounds (3a-e) were refluxed with different N-methylpiperazine and N-phenylpiperazine to afford 4-substituted-2-(4-methylpiperazin-1-yl)-6-(thiophen-2-yl)pyrimidines (4a-e) and 4-substituted-2-(4-phenylpiperazin-1-yl)-6-(thiophen-2-yl)pyrimidines (5a-e). The structures of all the newly synthesised compounds 4b, 4d, 5a and 5b showed good antibacterial activity at 40µg/mlconcentration. Compounds 4a, 4d, 4e, 5c and 5e showed significant antifungal activity at 40 µg/ml concentration compared with standard drugs.