Novel Carbazole–Formazan Derivatives: Synthesis, Spectroscopic Characterization, DFT Analysis, and Molecular Docking Studies

In this study, three novel chloro-substituted carbazole–formazan derivatives were synthesized through a diazotization–coupling reaction starting from carbazole-based hydrazone intermediates. The structures of the obtained compounds were elucidated using FT-IR, ¹H NMR, ¹³C NMR, and HRMS spectroscopy (for the p-chloro derivative), all of which confirmed the successful formation of the azo–hydrazone tautomeric framework. FT-IR spectra exhibited characteristic N–H, C=N, N=N, and C–N stretching vibrations, while the NMR data clearly reflected the electronic environments of the carbazole scaffold and the substituted formazan moiety. To investigate the electronic and structural features of the synthesized regioisomers, Density Functional Theory (DFT) calculations were performed, including frontier molecular orbital (FMO) analysis, molecular electrostatic potential (MEP) mapping, and global reactivity descriptors. The results revealed that the position of the chloro substituent significantly influences orbital distributions, charge separation, and overall reactivity. The ortho isomer exhibited the lowest HOMO–LUMO energy gap and highest electrophilicity, indicating enhanced reactivity. In contrast, the para isomer displayed the greatest chemical hardness and π-delocalization, suggesting superior electronic stability. Molecular docking simulations were carried out against six clinically relevant microbial enzymes, including TEM-1 β-lactamase, AmpC β-lactamase, PBP2a, PBP5, CYP51B, and CYP51. All derivatives exhibited favorable binding energies, supported by diverse stabilizing interactions, including hydrogen bonding, π–π stacking, and hydrophobic contacts. Among them, the p-chloro derivative demonstrated the strongest binding affinities, consistent with its DFT-derived stability and electron distribution. Overall, the combined spectroscopic, computational, and molecular docking results highlight these carbazole–formazan derivatives as promising scaffolds with potential antimicrobial relevance. The findings provide a robust foundation for future biological evaluation and rational structural optimization.