Pt(II) complexes with N,O-chelating Schiff base ligands: synthesis, spectroscopic characterization, biomolecular binding, and cytotoxicity

In this work, three Pt(II) complexes containing benzophenone-derived Schiff base ligands with the proposed general formula K[PtCl 2 (L)] were synthesized in a 1:1 metal-to-ligand ratio, where HL1 is propylamine-5-chloro-2-hydroxybenzophenone, HL2 is butylamine-5-chloro-2-hydroxybenzophenone, and HL3 is propylamine-2,2ˮ-dihydroxy-4-methoxybenzophenone. Upon coordination, the ligands were deprotonated to form L − species. Elemental analysis, UV–Vis, FT-IR, and NMR spectroscopy provided evidence for coordination through the imine nitrogen and phenolic oxygen atoms and were consistent with the proposed N,O -chelation mode in the Pt(II) complexes. The p K a values were determined by spectrophotometric absorbance–pH titrations. Nonlinear fitting of the experimental data revealed two apparent acidity constants for each system, with p K a1 values ranging from 3.49 to 3.82 and p K a2 values ranging from 5.48 to 6.76. The apparent acidity constants were tentatively assigned to pH-dependent processes involving the corresponding diaqua species generated in solution. ADMET calculations indicated that the free ligands comply with Lipinski's rule of five and possess physicochemical properties typical of small organic molecules. Upon coordination, increased lipophilicity, high plasma-protein binding, and low predicted AMES probabilities were observed. These predictions provide a comparative assessment but should be interpreted cautiously because current ADMET models are not optimized for metal-containing systems. DNA- and HSA-binding experiments indicated weak-to-moderate affinity, while preliminary cytotoxicity assays showed low biological activity. Molecular docking predicted these findings, with complex 3 displaying the most favorable interaction profile, providing a basis for future structural optimization.