Coordination-guided design of triazole-based Cu(ii) and Pt(iv) complexes: synthesis, characterization, theoretical studies, molecular docking and anticancer activity.

A new triazole-based ligand (L) was synthesized via a Schiff base condensation between 4-6-methoxy-2-naphthaldehyde and amino-5-(3,4,5-trimethoxyphenyl)-2H-1,2,4-triazole-3-thione, and its structure was confirmed using FT-IR, NMR, and UV-vis spectroscopy and mass spectrometry analysis. The ligand L was complexed with Cu(ii) and Pt(iv) ions to yield LCu and LPt complexes, respectively. The synthesized complexes were characterized by FT-IR spectroscopy, elemental analysis, UV-vis spectroscopy and magnetic susceptibility measurements. The spectroscopic and magnetic measurements indicated square planar and octahedral geometries for the LCu and LPt complexes, respectively, consistent with the results from DFT and TD-DFT calculations. Theoretical investigations confirmed the experimental UV-vis transitions and revealed pronounced metal-ligand charge transfer features. Cytotoxic evaluation against the SK-OV-3 ovarian cancer and HDFa normal cell lines demonstrated a marked improvement in the anticancer activity upon coordination, with LPt showing the lowest IC50 value (24.85 µg mL-1) and the highest selectivity index (16.54). Molecular docking studies with tubulin (PDB: 8QEA) and estrogen receptor α (PDB: 3ERT) supported these findings, showing the strong binding affinity of LPt (-6.920 kcal mol-1) mediated by hydrogen bonding with ASN256 (2.97 Å, 1.4 kcal mol-1) and π-H interactions between its six-membered ring system and PRO259 (4.62 Å, -0.6 kcal mol-1). Overall, the designed triazole ligand represents an effective molecular scaffold, and its Pt(iv) complex (LPt) emerges as a promising anticancer agent targeting microtubule polymerization and estrogen receptor pathways.