Unveiling the bioactive potential of organotin(IV) complexes of hydrazones: Synthesis, spectral characterization, in vitro and in silico exploration

In the quest of compounds with potent antimicrobial and antioxidant properties, we conducted a comprehensive investigation involving four hydrazone ligands [H2L1-4] (1-4) and their respective sixteen organotin(IV) complexes (5-20) with general formula R '' 2SnL1-4 [R '' = Me, Et, Bu, Ph]. Various spectroscopic and physicochemical studies were employed for the thorough characterization of the synthesized compounds, which demonstrated the tridentate chelation of ligands via ONO donor domains by O-phenolic, N-azomethine and O-enolic atoms displaying pentacoordinated geometry. Further, the compounds were subjected to bioactivity assays by targeting their in vitro antioxidant and antimicrobial studies. Complex 8 [Ph2SnL1], 12 [Ph2SnL2], 16 [Ph2SnL3], 19 [Bu2SnL4] and 20 [Ph2SnL4] emerged as particularly noteworthy antimicrobials, exhibiting a higher level of inhibition having minimum inhibition concentration (MIC) value in the range of 0.0042-0.0095 mu mol/mL. Among them, complex 20 exhibited superior activity with MIC values of 0.0042 mu mol/mL against C. albicans and S. aureus, surpassing the standard drugs ciprofloxacin (0.0047 mu mol/mL) and fluconazole (0.0051 mu mol/mL). Additionally, all the compounds showed notable radical scavenging activity, and the activity of complexes increases in the order Ph2SnL1-4 (1.93-3.68 mu M) > Bu2SnL1-4 (2.26-4.15 mu M) > Et2SnL1-4 (2.91-4.97 mu M) > Me2SnL1-4 (3.49-5.10 mu M) (DPPH assay). Furthermore, In silico studies including Molecular docking, Density Functional Theory (DFT), Molecular Electrostatic Potential (MESP), Absorption, Distribution, Metabolism, Excretion and Toxicity ADMET) analysis highlighted the significance of highly potent antimicrobial compounds (4, 17-20) as potential drug candidates. Each compound exhibited binding affinity with protein binding site, including carbon-hydrogen bonds, conventional hydrogen bonds, alkyl interactions and pi-alkyl interactions. Compound 20 exhibited a superior docking score of -137.644 kcal/mol at the active site of C. albicans (PDB ID: 4HOE). The binding energy of the compounds followed the order: 20 (-11.6577 eV) < 19 (-11.3193 eV) < 18 (-9.23989 eV) < 17 (-8.23386 eV) < 4 (-7.01131 eV) and coincided well with the findings of experimental research. In summary, this comprehensive research underscores the substantial biological activity of the synthesized compounds and their promising potential for future applications in drug development.