title: Non-covalent DNA binding and cytotoxicity of certain mixed-ligand ruthenium(II) complexes of 2,2'-dipyridylamine and diimines.
abstract: A series of mixed ligand ruthenium(II) complexes [Ru(Hdpa)2(diimine)](ClO4)2, 1-5 where Hdpa is 2,2'-dipyridylamine and diimine is 1,10-phenanthroline (phen) and a modified/extended 1,10-phenanthroline such as, 5,6-dimethyl-1,10-phenanthroline (5,6-dmp), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), 5-methyldipyrido[3,2-d:2',3'-f]quinoxaline (mdpq) and dipyrido[3,2-a:2',3'-c]phenazine (dppz) have been isolated and characterized by analytical and spectral methods. The complex [Ru(Hdpa)2(phen)](PF6)2 1 has been structurally characterized and the coordination geometry around Ru(II) in it is described as distorted octahedral. 1H NMR spectral data reveal that 1-5 should have a C2 symmetry lying on the diimine plane due to the rapid flapping of the coordinated Hdpa ligands. The interaction of the complexes with calf thymus (CT) DNA has been explored by using absorption and emission spectral and viscometry and electrochemical techniques and the mode of DNA binding of the complexes has been proposed. The DNA binding affinity of the complexes decreases with decrease in number of planar aromatic rings in the co-ligand supporting the intercalation of the diimine co-ligands in between the DNA base pairs. Circular dichroic spectral studies reveal that the complexes 3-5 exhibit induced circular dichroism upon binding to CT DNA. Interestingly, upon interaction with CT DNA all the complexes show an increase in anodic current in the cyclic voltammograms suggesting that they are involved in electrocatalytic guanine oxidation. Interestingly, of all the complexes, only 5 alters the DNA superhelicity upon binding with supercoiled pBR322 DNA, which is consistent with its higher DNA binding affinity. Further, the cytotoxicities of the complexes against human cervical epidermoid carcinoma cell line (ME180) have been examined. Interestingly, 5 exhibits a cytotoxicity against ME180 higher than other complexes with potency approximately 8 times more than cisplatin for 24 h incubation but 4 times lower than cisplatin for 48 h incubation.
authors.affiliation: School of Chemistry, Bharathidasan University, Tiruchirappalli, 620 024, Tamilnadu, India.
authors.forename: Venugopal
authors.initials: V
authors.lastname: Rajendiran
authors.forename: Mariappan
authors.initials: M
authors.lastname: Murali
authors.forename: Eringathodi
authors.initials: E
authors.lastname: Suresh
authors.forename: Mallayan
authors.initials: M
authors.lastname: Palaniandavar
authors.forename: Vaiyapuri Subbarayan
authors.initials: VS
authors.lastname: Periasamy
authors.forename: Mohammad Abdulkader
authors.initials: MA
authors.lastname: Akbarsha
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004563:Electrochemistry; D004996:Ethidium / Q000737:chemistry; D005260:Female; D006801:Humans; D007097:Imines / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012428:Ruthenium / Q000737:chemistry* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*; D014783:Viscosity
chemical_list: D007097:Imines; D008024:Ligands; D009942:Organometallic Compounds; D015082:2,2'-Dipyridyl; D012428:Ruthenium; D004247:DNA; D004996:Ethidium; C048062:2,2'-dipyridylamine