Synthesis, characterisation, In Silico analysis, and antimicrobial evaluation of mixed-ligand metal (II) complexes of quercetin-8-sulphonic acid and citric acid

Abstract

A sulphonic derivative of quercetin and its four new mixed-ligand metal (II) complexes involving citric acid were synthesized, characterized, and tested against resistant bacteria and fungi. Characterization involved physicochemical techniques, elemental analysis, ultraviolet visible spectroscopy (Uv-Vis), Fourier transform infra-red spectroscopy (FTIR), Atomic absorption spectroscopy (AAS), Nuclear magnetic resonance (NMR) spectroscopy, and conductivity measurements. Elemental analysis results closely matched theoretical values. Conductivity studies indicated non-electrolytic behaviour and suggested octahedral geometry. Spectroscopic analyses confirmed complex formation, while NMR spectra identified substitution positions on the quercetin rings. Antimicrobial studies revealed that Manganese complex of quercetin-8-sulponic acid and citric acid [Mn(Q8SA)(CA)]Cl exhibited the highest antibacterial activity against Pseudomonas aeruginosa (35±1.2 mm at 100 µg/ml) compared to the sulphonic derivative (20±1.4 mm) and quercetin (16±1.5 mm). Cobalt complex of quercetin-8-sulphonic acid and citric acid [Co(Q8SA)(CA)]Cl showed the highest antifungal activity against Aspergillus flavus (25±1.3 mm at 50 µg/ml; 28±2.1 mm at 100 µg/ml) compared to the sulphonic derivative and quercetin (9±1.3 mm; 12±1.0 mm). Molecular docking revealed strong binding affinities (-11.0 to -8.0 kcal/mol among the complexes) surpassing quercetin and the derivative. However, biochemical parameters prediction disqualifies the complexes as potential drug candidates according to Lipinski’s rule of 5. Antimicrobial effectiveness was concentration-dependent. The mixed-ligand metal (II) complexes exhibited superior chemical and biological properties compared to quercetin-8-sulphonic derivative, which in turn is better than standard quercetin in vivo, highlighting the potential of organic modification and metal coordination in addressing microbial resistance.