title: 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.
abstract: 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.
authors.affiliation: School of Chemistry, Bharathidasan University, Tiruchirappalli 620 024, Tamil Nadu, India.
authors.forename: Chandrasekaran
authors.initials: C
authors.lastname: Rajarajeswari
authors.affiliation: Department of Chemistry, Central University of Tamil Nadu, Thiruvarur 610004, Tamil Nadu, India.
authors.forename: Mani
authors.initials: M
authors.lastname: Ganeshpandian
authors.affiliation: Department of Chemistry, Central University of Tamil Nadu, Thiruvarur 610004, Tamil Nadu, India. Electronic address: palanim51@yahoo.com.
authors.forename: Mallayan
authors.initials: M
authors.lastname: Palaniandavar
authors.affiliation: Department of Animal Science, Bharathidasan University, Tiruchirappalli 620 024, Tamil Nadu, India.
authors.forename: Anvarbatcha
authors.initials: A
authors.lastname: Riyasdeen
authors.affiliation: Mahatma Gandhi-Doerenkamp Center for Alternatives to use of Animals in Life Science Education, Bharathidasan University, Tiruchirappalli, 620024, Tamil Nadu, India; Department of Food Sciences and Nutrition, College of Food Sciences and Agriculture, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia.
authors.forename: Mohammad Abdulkadher
authors.initials: MA
authors.lastname: Akbarsha
mesh_terms: D001665:Binding Sites; D002470:Cell Survival; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism*; D006868:Hydrolysis; D062385:Hydroxybenzoates / Q000737:chemistry; D007093:Imidazoles / Q000737:chemistry; D008024:Ligands; D010618:Phenanthrolines / Q000737:chemistry* / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry; D012545:Schiff Bases / Q000737:chemistry*
chemical_list: D062385:Hydroxybenzoates; D007093:Imidazoles; D008024:Ligands; D010618:Phenanthrolines; D011725:Pyridines; D012545:Schiff Bases; D003300:Copper; D004247:DNA; C017616:phenolic acid; C023666:pyridine; C025205:1,10-phenanthroline
keywords: Cytotoxicity; DNA binding; Mixed ligand Cu(II) phen complexes; Oxidative DNA cleavage; Tridentate Schiff base ligands