Mixed ligand copper(II) complexes of 2,9-dimethyl-1,10-phenanthroline: Tridentate 3N primary ligands determine DNA binding and cleavage and cytotoxicity

作者：Ganeshpandian Mani; Ramakrishnan Sethu; Palaniandavar Mallayan^*; Suresh Eringathodi; Riyasdeen Anvarbatcha; Akbarsha Mohammad Abdulkadher

来源：Journal of Inorganic Biochemistry, 2014, 140: 202-212.

DOI：10.1016/j.jinorgbio.2014.07.021

• Mixed ligand copper(II) complexes
• 2,9-Dimethyl-1,10-phenanthroline
• Hydrogen bonding potential
• Hydrophobicity
• Cell cycle arrest

A series of mononuclear mixed ligand copper(II) complexes of the type [Cu(L)(2,9-dmP)](ClO4)(2) 1-4, where L is a tridentate 3N ligand such as diethylenetriamine (L1) (1) or N-methyl-N%26apos;-(pyrid-2-yl-methyl)ethylenediamine (L2) (2) or di(2-picolyl)amine (L3) (3) or bis(pyrid-2-ylmethyl)-N-methylamine (L4) (4) and 2,9-dmp is 2,9-dimethyl-1,10-phenanthroline, has been isolated and characterized. The complexes 1 and 3 possess square-based pyramidal coordination geometry. Absorption spectral studies reveal that the intrinsic DNA binding affinity varies as 1 %26gt; 2 %26gt; 3 %26gt; 4. The higher DNA binding affinity of 1 arises from L1, which offers lower steric hindrance toward intercalation of 2,9-dmp co-ligand into DNA base pairs and is involved in hydrogen bonding interaction with DNA. Interestingly, all the complexes cleave pUC19 supercoiled DNA in the absence of an activating agent. They also exhibit oxidative (H2O2) DNA cleavage ability, which varies as 1 %26gt; 2 %26gt; 3 %26gt; 4, the highest cleavage efficiency of 1 being due to the largest amount of ROS it generates. The typtophan emission-quenching experiment reveals that the stronger binding of 3 and 4 with bovine serum albumin (BSA) in the hydrophobic region, which is in line with DNA viscosity measurements. The IC50 values of 1-4 for MCF-7 breast cancer cell line are lower than that of cisplatin. Flow cytometry analysis reveals that 1 mediates the arrest of S and G2/M phases in the cell cycle progression at 24 h harvesting time, which progresses into apoptosis. Hoechst 33258 staining studies indicate the higher potency of 1 to induce apoptosis.

• 出版日期2014-11
• 单位海洋化工研究院有限公司