title: Synthesis, electronic structure, DNA and protein binding, DNA cleavage, and anticancer activity of fluorophore-labeled copper(II) complexes.
abstract: Two mononuclear fluorophore-labeled copper(II) complexes [Cu(nip)(acac)](+)(2) and [Cu(nip)2](2+) (3), where fluorophore is 2-(naphthalen-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (nip) (1) and acac is acetylacetone, have been synthesized and characterized by various techniques. The ligand 1 and complex 2 are structurally characterized by single-crystal X-ray diffraction. The coordination geometries around the copper are square planar in solid as well as solution state as evidenced by electron paramagnetic resonance (EPR) spectroscopy. The density functional calculations carried out on 1-3 have shown that electron-rich regions in the highest occupied orbital are localized on the naphthalene and partly on the phenanthroline moiety. Both complexes 2 and 3 in dimethyl sulfoxide (DMSO) exhibit near square planar structure around the metal ion in their ground state. Time-dependent density functional theory (TD-DFT) calculations reveal that Cu(II) ion in complex 2 shows tetrahedral coordination around the metal while 3 retains its square planar geometry in the lowest excited state. The interaction of complexes with calf-thymus DNA (CT DNA) has been explored by using absorption, emission, thermal denaturation, and viscosity studies, and the intercalating mode of DNA binding has been proposed. The complexes cleave DNA oxidatively without any exogenous additives. The protein binding ability has been monitored by quenching of tryptophan emission in the presence of complexes using bovine serum albumin (BSA) as model protein. The compounds showed dynamic quenching behavior. Further, the anticancer activity of the complexes on MCF-7 (human breast cancer), HeLa (human cervical cancer), HL-60 (human promyelocytic leukemia), and MCF-12A (normal epithelial) cell lines has been studied. It has been observed that 3 exhibits higher cytotoxicity than 2, and the cells undergo apoptotic cell death.
authors.affiliation: Department of Chemistry, University of Pune, Pune 411007, India.
authors.forename: Satish S
authors.initials: SS
authors.lastname: Bhat
authors.forename: Anupa A
authors.initials: AA
authors.lastname: Kumbhar
authors.forename: Hussain
authors.initials: H
authors.lastname: Heptullah
authors.forename: Ayesha A
authors.initials: AA
authors.lastname: Khan
authors.forename: Vivekanand V
authors.initials: VV
authors.lastname: Gobre
authors.forename: Shridhar P
authors.initials: SP
authors.lastname: Gejji
authors.forename: Vedavati G
authors.initials: VG
authors.lastname: Puranik
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D019295:Computational Biology; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D053837:DNA Cleavage / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D012260:Ribonucleases / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D013778:Tetrazolium Salts; D013844:Thiazoles; D012710:Serum Albumin, Bovine; D003300:Copper; D004247:DNA; C427203:calf thymus DNA; D012260:Ribonucleases; C022616:thiazolyl blue