title: Remarkable anticancer activity of ferrocenyl-terpyridine platinum(ii) complexes in visible light with low dark toxicity.
abstract: Ferrocenyl platinum(ii) complexes (), viz. [Pt(Fc-tpy)Cl]Cl (), [Pt(Fc-tpy)(NPC)]Cl (, HNPC = N-propargyl carbazole) and [Pt(Fc-bpa)Cl]Cl (), were prepared, characterized and their anti-proliferative properties in visible light in human keratinocyte (HaCaT) cell lines have been studied. [Pt(Ph-tpy)Cl]Cl () was prepared and used as a control. Complexes and , structurally characterized by X-ray crystallography, show distorted square-planar geometry for the platinum(ii) centre. Complexes and having the Fc-tpy ligand showed an intense absorption band at ∼590 nm. The ferrocenyl complexes are redox active showing the Fc(+)-Fc couple near 0.6 V vs. SCE in DMF-0.1 M tetrabutylammonium perchlorate (TBAP). Complexes showed external binding to calf thymus DNA. Both and showed remarkable photocytotoxicity in HaCaT cell lines giving respective IC50 values of 9.8 and 12.0 μM in visible light of 400-700 nm with low dark toxicity (IC50 >60 μM). Fluorescent imaging studies showed the spread of the complexes throughout the cell localising both in cytoplasm and the nucleus. The ferrocenyl complexes triggered apoptosis on light exposure as evidenced from the Annexin V-FITC/PI and DNA ladder formation assays. Spectral studies revealed the formation of ferrocenium ions upon photo-irradiation generating cytotoxic hydroxyl radicals via a Fenton type mechanism. The results are rationalized from a TDDFT study that shows involvement of ferrocene and the platinum coordinated terpyridine moiety as respective HOMO and LUMO.
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, India. arc@ipc.iisc.ernet.in.
authors.forename: Koushambi
authors.initials: K
authors.lastname: Mitra
authors.forename: Uttara
authors.initials: U
authors.lastname: Basu
authors.forename: Imran
authors.initials: I
authors.lastname: Khan
authors.forename: Basudev
authors.initials: B
authors.lastname: Maity
authors.forename: Paturu
authors.initials: P
authors.lastname: Kondaiah
authors.forename: Akhil R
authors.initials: AR
authors.lastname: Chakravarty
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport; D002453:Cell Cycle / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D053837:DNA Cleavage / Q000187:drug effects; D003624:Darkness; D004355:Drug Stability; D005296:Ferrous Compounds / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity*; D055668:Photochemical Processes; D010778:Photochemotherapy; D011725:Pyridines / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D005296:Ferrous Compounds; D009944:Organoplatinum Compounds; D011725:Pyridines; D017382:Reactive Oxygen Species; C064804:ferrocenium; D004247:DNA; C427203:calf thymus DNA; C023666:pyridine