Synthesis, characterization and DNA interaction of a novel Pt(II) macroacyclic Schiff base complex containing the piperazine moiety and its cytotoxicity and molecular docking

Abstract

A new platinum Schiff base complex, [C17H28N4OPt]Cl2 (1) was prepared from the condensation of a polyamine containing piperazine moiety, (1,4-bis(3-aminopropyl)piperazine) and 2-hydroxy-benzaldehyde (H2L), in the presence of Pt2+ ion and examined by mass, FT-IR, elemental analysis 1H NMR and 13C NMR. The structure of the metal complex has been confirmed by a single-crystal X-ray structural analysis in which the Pt atom is in a square planar coordination environment. The crystal was found to be composed of two complexes that co-crystallized, the formulation being 0.973[C17H28N4OPt]Cl2, 0.014[[C17H27N4OPt]2PtCl2]Cl2. The ligand and Schiff base complex interactions with calf thymus DNA (ct-DNA) were studied using UV–Vis and fluorescence spectroscopy and molecular docking simulations. UV–Vis absorption investigations indicated hyprechromism and hypochromism effects, respectively, for the ligand and the complex. The binding constant of the Pt(II) complex with DNA (6.1 × 104 M−1) was greater than the corresponding binding value of the ligand (4 × 103 M−1). Competitive florescence results showed that molecular replacement of Hoechst in the minor groove of DNA by the ligand and Pt(II) complex resulted in the fluorescence of the DNA-Hoechst system being extinguished. Fluorescence emission spectra, using methylene blue (MB) as an intercalate probe, demonstrated only the replacement of MB by the Pt(II) complex from the MB-DNA system. Thermodynamic studies confirmed that van der Waals forces and hydrogen bonds play critical roles in the compounds-DNA binding. Based on the viscosity measurements, the effect of the ligand on DNA viscosity was less than that of the Pt(II) complex. The experimental results were supported by molecular docking studies. The results showed that the Pt(II) complex interacts with DNA via a partial intercalation mode, while the free ligand showed binding to DNA in the minor groove. In vitro cell, culture studies confirmed that the Pt(II) complex has a remarkable cytotoxic effect on human prostate carcinoma cells.