Synthesis, characterization, DNA interaction, cytotoxicity, and apoptosis induction of a mixed-ligand copper(II) complex

Abstract

A mixed-ligand complex, [Cu(Hptc)(Me₂bpy)(H₂O)]·3H₂O (1) (H₃ptc = pyridine-2,4,6-tricarboxylic acid; Me₂bpy = 4,4′-dimethyl-2,2′-dipyridine), has been synthesized and characterized by elemental analysis, IR, and single-crystal X-ray diffraction. In the discrete mononuclear structure of 1, the copper core is in a distorted octahedral environment (CuN₃O₃) derived from tridentate chelate Hptc²⁻, bidentate chelate Me₂bpy and a coordinated water. The interaction of 1 with CT-DNA was investigated by UV–vis spectra, fluorescence spectra and viscosity, which reveals that 1 binds to CT-DNA by partial intercalation. Gel electrophoresis assay demonstrated that the complex displays efficient oxidative cleavage of supercoiled DNA with H₂O₂ as an oxidant. The in vitro cytotoxicity of 1 on HeLa cells was assessed by MTT and clonogenic assay, where IC₅₀ equals 4.24 ± 0.03 μM. Fluorescence microscopic observations indicated that 1 can induce apoptosis of HeLa cells.

Keywords:

• Copper complex
• Pyridine-2,4,6-tricarboxylic acid
• DNA interaction
• Cytotoxicity
• Apoptosis

Funding

This study was supported by the National Natural Science Foundation of China [grant number 21371135], [grant number 20971099]; and the Key Program of Tianjin Municipal Natural Science Foundation [grant number 13JCZDJC28200].