title: DNA Binding and Photocleavage Properties, Cellular Uptake and Localization, and in-Vitro Cytotoxicity of Dinuclear Ruthenium(II) Complexes with Varying Lengths in Bridging Alkyl Linkers.
abstract: Two new dinuclear Ru(II) polypyridyl complexes containing three and ten methylene chains in their bridging linkers are synthesized and characterized. Their calf thymus DNA-binding and plasmid DNA photocleavage behaviors are comparatively studied with a previously reported, six-methylene-containing analog by absorption and luminescence spectroscopy, steady-state emission quenching by [Fe(CN)6](4-), DNA competitive binding with ethidium bromide, DNA viscosity measurements, DNA thermal denaturation, and agarose gel electrophoresis analyses. Theoretical calculations applying the density functional theory (DFT) method for the three complexes are also performed to understand experimentally observed DNA binding properties. The results show that the two complexes partially intercalate between the base pairs of DNA. Cellular uptake and colocalization studies have demonstrated that the complexes could enter HeLa cells efficiently and localize within lysosomes. The in-vitro antitumor activity against HeLa and MCF-7 tumor cells of the complexes are studied by MTT cytotoxic analysis. A new method, high-content analysis (HCA), is also used to assess cytotoxicity, apoptosis and cell cycle arrest of the three complexes. The results show that the lengths of the alkyl linkers could effectively tune their biological properties and that HCA is suitable for rapidly identifying cytotoxicity and can be substituted for MTT assays to evaluate the cell cytotoxicity of chemotherapeutic agents.
authors.affiliation: Beijing Key Laboratory of Energy Conversion and Storage Materials, and Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, and ‡College of Life Sciences, Beijing Normal University , Beijing 100875, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Beijing Key Laboratory of Energy Conversion and Storage Materials, and Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, and ‡College of Life Sciences, Beijing Normal University , Beijing 100875, P.R. China.
authors.forename: Bao-Yan
authors.initials: BY
authors.lastname: Wu
authors.affiliation: Beijing Key Laboratory of Energy Conversion and Storage Materials, and Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, and ‡College of Life Sciences, Beijing Normal University , Beijing 100875, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Beijing Key Laboratory of Energy Conversion and Storage Materials, and Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, and ‡College of Life Sciences, Beijing Normal University , Beijing 100875, P.R. China.
authors.forename: Yong-Cheng
authors.initials: YC
authors.lastname: Dai
authors.affiliation: Beijing Key Laboratory of Energy Conversion and Storage Materials, and Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, and ‡College of Life Sciences, Beijing Normal University , Beijing 100875, P.R. China.
authors.forename: You-Jun
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Energy Conversion and Storage Materials, and Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, and ‡College of Life Sciences, Beijing Normal University , Beijing 100875, P.R. China.
authors.forename: Ke-Zhi
authors.initials: KZ
authors.lastname: Wang
mesh_terms: D004247:DNA / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D004587:Electrophoresis, Agar Gel; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D061986:MCF-7 Cells; D055668:Photochemical Processes; D017975:Ruthenium Compounds / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D017975:Ruthenium Compounds; D004247:DNA