Structural-property relationship in Pt(N^{NO})Cl: The effect of hydrogenating the Schiff base ligand on spectral, biomolecule-binding and anticancer properties

Abstract

Tridentate Schiff base ligand (L) was synthesized from reactions of N-phenyl-1,2-diaminobenzene and 3-ethoxysalicylaldehyde. The Schiff base was hydrogenated by sodium borohydride to produce the second ligand (HL). Complexes with the general formula Pt(N^{NO})Cl were synthesized by reacting K₂PtCl₄ with the ligands in DMSO/ethanol mixtures, generating L-Pt and HL-Pt complexes. The ligand and its complex were characterized by NMR spectroscopy, mass spectrometry and elemental analysis. The DNA-binding of the platinum(II) compounds were evaluated by following changes induced on the viscosity of ct-DNA, indicating covalent binding mode with ct-DNA. L-Pt is strongly emissive with emission maximum ca. 630 nm, which complicated the evaluation of DNA- and BSA-binding by the fluorescence quenching technique. However, HL-Pt has good binding affinities with ct-DNA with apparent binding constant of 1.0 × 10⁶ while BSA-binding studies indicated static quenching process with binding constant (K_b) value equals to 1.43 × 10⁶. The half maximal inhibitory concentrations (IC₅₀) values against MCF-7 and HepG2 suggest that L-Pt has better cytotoxic effect compared to that of HL-Pt and cisplatin. Although, both L-Pt and HL-Pt were more cytotoxic towards the normal cell line. The flow cytometry assay indicated that L-Pt, HL-Pt and cisplatin induce their cytotoxic effect by apoptosis. However, the cell cycle arrest of L-Pt and HL-Pt on MCF-7 show similar pattern but it is different to that of MCF-7 treated with cisplatin, suggesting different mechanism in activating the cell death. DFT calculations were employed to stimulate the binding of L-Pt and HL-Pt with a fragment of DNA (trimer), highlighting the effect of the ligands. In conclusion, the current study highlight the importance of the azomethine linkage in the ligand on the anticancer properties on the complexes of the type Pt(N^{NO})Cl.