title: Efficient DNA cleavage mediated by mononuclear mixed ligand copper(II) phenolate complexes: the role of co-ligand planarity on DNA binding and cleavage and anticancer activity.
abstract: The new mononuclear copper(II) complexes [Cu(L)(H(2)O)(2)](+)1 and [Cu(L)(diimine)](+)2-6, where LH=2-[(2-dimethylaminoethylimino)methyl]phenol and diimine=2,2'-bipyridine (bpy) (2), or 1,10-phenanthroline (phen) (3), or dipyrido[3,2-f:2',3'-h]quinoxaline (dpq) (4) or dipyrido[3,2-a:2',3'-c]phenazine (dppz) (5) or 11,12-dimethyldipyrido[3,2-a:2',3'-c]phenazine (dmdppz) (6), have been isolated and characterized. The X-ray crystal structures of 2 contains the monomeric complex molecule with a trigonal bipyramidal distorted square pyramidal (TBPDSP) coordination geometry, while 4 and 6 with square pyramidal distorted trigonal bipyramidal (SPDTBP) coordination geometry. The amine nitrogen of -NMe(2) group of the tridentate primary ligand is located at one of the corners of the square plane in 2 and 6 but in the axial position in 4. The interaction of the complexes with calf thymus DNA has been investigated using UV-visible and fluorescence spectroscopy, and viscosity measurements to understand the effect of diimine co-ligands on the mode and extent of DNA binding. The complexes 4 and 5 interact with calf thymus DNA more strongly than the other complexes through partial intercalation of the extended planar ring of the dpq (4) and dppz (5) co-ligands with the DNA base stack. All the complexes, except 1, effect the double strand DNA cleavage of plasmid DNA and 5 cleaves plasmid DNA in the absence of a reductant at a concentration (40 μM) lower than 4. It is remarkable that all the complexes display cytotoxicity against human breast cancer cell lines (MCF-7) and human cervical epidermoid carcinoma cell lines (ME 180) with potency higher than the currently used chemotherapeutic agent cisplatin and that 5 exhibits cytotoxicity higher than the other complexes.
authors: Centre for Bioinorganic Chemistry, School of Chemistry, Bharathidasan University, Tiruchirappalli 620024, Tamil Nadu, India.
authors: Paramasivam
authors: P
authors: Jaividhya
authors: Rajkumar
authors: R
authors: Dhivya
authors: Mohamad Abdulkadhar
authors: MA
authors: Akbarsha
authors: Mallayan
authors: M
authors: Palaniandavar
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000494:pharmacology; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry; D053837:DNA Cleavage / Q000187:drug effects*; D005260:Female; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D010618:Phenanthrolines / Q000737:chemistry; D010619:Phenazines / Q000737:chemistry; D010636:Phenols / Q000737:chemistry*; D011810:Quinoxalines / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008024:Ligands; D010618:Phenanthrolines; D010619:Phenazines; D010636:Phenols; D011810:Quinoxalines; D015082:2,2'-Dipyridyl; D003300:Copper; D004247:DNA; C427203:calf thymus DNA; C025205:1,10-phenanthroline