Fabrication, spectral characterisation and exploration of DNA/RNA binding affinity and biological potential of transition metal complexes incorporating isoniazid and aromatic nitrogen-donor ligands

Four mixed-ligand transition metal(II) complexes, [ML(L1)Cl2] (where M = Co, Ni, Cu, and Zn; L = Schiff base derived from isoniazid and 3-nitrobenzaldehyde; L1 = 1,10-phenanthroline), were synthesised and characterised using elemental analysis, FT-IR, UV-Vis, 1H NMR, EPR (for Cu), and molar conductance measurements. Physicochemical and spectroscopic data suggested an octahedral geometry for all complexes. Antimicrobial assays revealed that the complexes exhibited greater activity than the free Schiff base ligand, with inhibition zones of 14–22 mm against Staphylococcus aureus and Escherichia coli, compared to 8–12 mm for the free ligand. Similarly, antifungal screening showed zones of 12–20 mm against Candida albicans and Aspergillus niger. Predicted drug-likeness and pharmacokinetic properties using the SWISSADME tool indicated favourable absorption and permeability. DNA/RNA binding studies demonstrated intercalative interaction, with binding constants (Kb) in the range of 5.12 × 10−4 to 6.89 × 10−4 M−1 and 6.12 × 10−4 to 7.25 × 10−4 M−1, supported by viscosity and UV-Vis titration data. Molecular docking against the antibacterial and antifungal targets (PDB IDs 1W5D and 8IWD) yielded binding energies between −8.1 and −9.2, and 8.8 and 10.1 kJ/mol highlighting π–π stacking and hydrogen-bonding interactions. In comparison to the free ligand, chelation and the auxiliary 1,10-phenanthroline improved the metal complexes’ overall biological activity.