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The sobering reality is that numerous infectious diseases can no longer be effectively treated with antibiotics, necessitating immediate attention and action. Therefore, this study explores a thiadiazol derivative for the purpose of elucidating its antibacterial efficacy against carbapenem-resistant Klebsiella pneumonia and Pseudomonas aeruginosa. Prior to this examination, the compound (DOP) under study was structurally and electronically investigated utilizing density functional theory (DFT) at the ωB97XD/6–311++G (d, p) level of theory. Interestingly, this comprehensive investigation encompassed spectral analyses including FT-IR, and UV-excitation all studied in different solvents including DMSO, water, and methanol. Results of the frontier molecular orbital (FMO) analysis, DOP_gas showcased the lowest energy gap of 3.943 eV, implying heightened reactivity. Substantially, results from the pharmacokinetic studies illuminated facets of distribution, metabolism, and toxicity. Thus, registering the compound to possess incredible drug-like properties suggesting no detriments in terms of treatment. Notwithstanding, resounding results from the molecular docking studies presented DOP exhibited notable binding affinities and formed strong conventional hydrogen bonds with specific residues, indicating robust interactions. Particularly, DOP_6V78 and DOP_4WEJ displayed the highest affinities of -11.0 kcal/mol and 10.1 kcal/mol against Klebsiella pneumonia and Pseudomonas aeruginosa, respectively. These findings underscore the potential therapeutic efficacy of DOP against Carbapenem-resistant strains, suggesting its favorable attributes in comparison to conventional drugs in terms of binding affinity and interaction strength.

This study is aimed at evaluating the impact of solvation on the structural, spectroscopy (UV, NMR, FT-IR), reactivity, bonding interactions, and the drug potential of Pyridine 4-Carbaldehyde Semi-carbazone (PCS) against the disease (cholera) causing protein in the Gram-negative bacterium; Vibrio cholerae. Notably, the study was carried out using both experimental and theoretical calculations based on density functional theory (DFT) at the GD3B/B3LYP/6–311G++(2D,2P) level of theory along with molecular docking. Results from the UV- spectrum showed very fair absorption levels across the different solvents used, with theoretical peaks at 463 nm, 467 nm, 470 nm and 468 nm for PCS_DMSO, PCS_ETOH, PCS_H2O and PCS_MEOH, respectively. The study reveals discrepancies between experimental and theoretical 1H NMR shifts. However, theoretical 13C NMR shifts show minute differences. RDG analysis reveals steric repulsions in the pyridine ring. Whereas, the investigation of electronic properties reveal that the decreasing order of PCS_DMSO (3.668 eV) > PCS_H2O (3.206 eV) > PCS_MEOH (3.202 eV) > PCS_ETOH (0.312 eV). The results of docking showed that PCS had binding affinities of -5.0 Kcal/mol with protein 7P3R and -5.4 Kcal/mol with protein 1XTC which happen to be much lesser than -10.2 Kcal/mol formed between erythromycin and 7P3R. However, erythromycin formed a non-feasible bonding interactions with 1XTC with biding affinity of 18.0 Kcal/mol. Results of the MD simulation showed that PCS-MEOH had a higher energy value than PCS-DMSO, PCS-ETOH, and PCS-H2, indicating that it can interact with other substances more effectively, disperse more quickly. These results from the various studied objectives, however, suggest Pyridine 4-Carbaldehyde Semi-carbazone to be a lead compound for tackling the incidence, distribution and prevalence of cholera.