title: Mononuclear iron(iii) complexes of tridentate ligands with efficient nuclease activity and studies of their cytotoxicity.
abstract: Mononuclear mono- and bis-chelated iron(iii) complexes [Fe(Phimp)(H2O)(OMe)Cl], 1, [Fe(Phimp)Cl2], 2, [Fe(Me-Phimp)Cl2], 3, [Fe(N-Phimp)Cl2], 4, [Fe(Phimp)2](ClO4), 5, [Fe(Me-Phimp)2](NO3)·H2O, 6·H2O, and [Fe(N-Phimp)2](ClO4), 7, derived from tridentate ligands, have been synthesised and characterized. The X-ray crystal structures of the complexes 2, 4, 5 and 6·H2O were determined. The high-spin iron(iii) complexes were redox active and exhibited the Fe(iii)/Fe(ii) couple. The DNA binding affinity of these complexes was assessed using absorption, fluorescent intercalator displacement assays and circular dichroism spectral studies. Gel electrophoresis studies with DNA and complexes 1, 2, 3 and 6 showed efficient nuclease activity via a hydroxyl radical generated through a Fenton-type reaction mechanism. In situ reactive oxygen species generation has been further supported via DPPH (2,2-diphenyl-1-picrylhydrazine) radical quenching studies as well as theoretical studies. The cytotoxicities of the complexes were determined using the MCF7 cell line; the cytotoxicities (IC50 values) obtained for 1, 2, 3 and 5 were 0.67 ± 0.31, 0.46 ± 0.07, 0.87 ± 0.25 and 1.53 ± 0.41 μM, respectively, and complexes 1-6 were found to be non-toxic to normal HEK cell lines. An acridine orange staining assay for the complexes (1-6) supported cell death, probably via an apoptotic mechanism.
authors.affiliation: Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee-247667, Uttarakhand, India. ghoshfcy@iitr.ernet.in.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Tyagi
authors.forename: Ajanta
authors.initials: A
authors.lastname: Chakraborty
authors.forename: Udai P
authors.initials: UP
authors.lastname: Singh
authors.forename: Partha
authors.initials: P
authors.lastname: Roy
authors.forename: Kaushik
authors.initials: K
authors.lastname: Ghosh
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism*; D003851:Deoxyribonucleases / Q000737:chemistry / Q000494:pharmacology; D005290:Ferric Compounds / Q000737:chemistry* / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D061986:MCF-7 Cells; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D005290:Ferric Compounds; D008024:Ligands; D004247:DNA; D003851:Deoxyribonucleases