Synthesis, DFT study, molecular docking and antibacterial evaluation of a nitrophenyl-thienochromenone azo ligand and its Mn(II), Co(II) and Fe(II) complexes

Abstract The nitrophenyl-substituted azo-thienochromenone ligand 3-amino-1-[(E)-(4-nitrophenyl)diazenyl]-4 H -thieno[3,4-c]chromen-4-one ( 2 ), obtained by diazo coupling on 3-amino-4 H -thieno[3,4-c]chromen-4-one prepared via a modified Gewald cyclisation, was reacted with MnCl₂·4H₂O, CoCl₂·6H₂O and FeSO₄·7H₂O to give three new complexes, 3 (Mn), 4 (Co) and 5 (Fe), characterised by HRESI-MS, UV-Vis, FT-IR, multinuclear/2D NMR and powder X-ray diffraction (PXRD), which together established bidentate coordination of the ligand through the lactone carbonyl oxygen and the deprotonated aromatic amine nitrogen, leaving the azo bridge and nitro group uncoordinated. DFT calculations (B3LYP/6-311 + + G(d,p)) showed the HOMO-LUMO gap narrowing on complexation in the order 4 (1.679 eV) < 5 (2.085 eV) < 3 (2.513 eV) < 2 (2.737 eV), with 4 showing the highest electrophilicity index (ω = 16.143 eV). Molecular docking against E. coli DNA gyrase (7AB4), S. aureus DNA gyrase (1MWT) and P. aeruginosa lectin LecB (4NG2) ranked 3 as the most promising candidate, outperforming ciprofloxacin on 7AB4 and 1MWT, and broth microdilution confirmed this trend, with 3 giving the lowest MICs of the series (16 µg/mL against E. coli and S. aureus) while 5 was the only bactericidal compound against P. aeruginosa (MBC/MIC = 1). Overall, complexation of 2 with Mn(II), Co(II) and Fe(II) consistently enhanced antibacterial activity relative to the free ligand, with the manganese complex 3 standing out as the most active and computationally consistent candidate, supporting azo-thienochromenone metal complexes as a viable platform for antibacterial drug development.