Mixed ligand copper(II) complexes of 1,10-phenanthroline with tridentate phenolate/pyridyl/(benz)imidazolyl Schiff base ligands: covalent vs non-covalent DNA binding, DNA cleavage and cytotoxicity

J Inorg Biochem. 2014 Nov;140:255-68. doi: 10.1016/j.jinorgbio.2014.07.016. Epub 2014 Aug 1.


A series of copper(II) complexes of the types [Cu(L)(phen)](ClO4) 1-2, where HL is a tridentate ligand with two nitrogen and one oxygen donor atoms (2NO) such as 2-(2-(1H-benzimidazol-2-yl)ethyliminomethyl)phenol (HL1) and 2-(2-(1H-benzimidazol-2-yl)ethyl-imino)methyl)-4-methylphenol (HL2), phen is 1,10-phenanthroline and [Cu(L)(phen)](ClO4)23-6, where L is a tridentate ligand with three nitrogen donor atoms (3N) such as (2-pyridin-2-ylethyl)pyridin-2-ylmethyleneamine (L3), 2-(1H-benzimidazol-2-yl)ethyl)-pyridin-2-yl-methyleneamine (L4), 2-(1H-benzimidazol-2-yl)ethyl)(1H-imidazol-2-ylmethylene)-amine (L5) and 2-(1H-benzimidazol-2-yl)ethyl)(4,4a-dihydroquinolin-2-ylmethylene)amine (L6), has been isolated and characterized by different spectral techniques. In single crystal X-ray structures, 1 possesses square pyramidal distorted trigonal bipyramidal (SPDTBP), geometry whereas 3 and 4 possess trigonal bipyramidal distorted square pyramidal (TBDSP) geometry. UV-Vis and fluorescence spectral studies reveal that the complexes 1-6 bind non-covalently to calf thymus DNA more strongly than the corresponding covalently bound chlorido complexes [Cu(2NO)Cl] 1a-2a and [Cu(3N)Cl2] 3a-6a. On prolonged incubation, all the complexes 1-6 exhibit double strand cleavage of supercoiled (SC) plasmid DNA in the absence of an activator. Also, they exhibit cytotoxicity against human breast cancer cell lines (HBL-100) more potent than their corresponding chlorido complexes 1a-6a, and have the potential to act as efficient cytotoxic drugs.

Keywords: Cytotoxicity; DNA binding; Mixed ligand Cu(II) phen complexes; Oxidative DNA cleavage; Tridentate Schiff base ligands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Survival*
  • Copper / chemistry*
  • Crystallography, X-Ray
  • DNA / metabolism*
  • Hydrolysis
  • Hydroxybenzoates / chemistry
  • Imidazoles / chemistry
  • Ligands
  • Phenanthrolines / chemistry*
  • Phenanthrolines / metabolism
  • Pyridines / chemistry
  • Schiff Bases / chemistry*


  • Hydroxybenzoates
  • Imidazoles
  • Ligands
  • Phenanthrolines
  • Pyridines
  • Schiff Bases
  • Copper
  • DNA
  • phenolic acid
  • pyridine
  • 1,10-phenanthroline