title: 2-Nitroimidazole-ruthenium polypyridyl complex as a new conjugate for cancer treatment and visualization.
abstract: A novel long-lifetime highly luminescent ruthenium polypyridyl complex containing 2-nitroimidazole moiety [Ru(dip)2(bpy-2-nitroIm)]Cl2 (dip=4,7-diphenyl-1,10-phenanthroline, bpy-2-nitroIm=4-[3-(2-nitro-1H-imidazol-1-yl)propyl]-2,2'-bipyridine) has been designed cancer treatment and imaging. The luminescence properties of the synthesized compound strongly depend on the oxygen concentration. Under oxygen-free conditions quantum yield of luminescence and the average lifetime of emission were found to be 0.034 and 1.9 μs, respectively, which is ca. three times higher in comparison to values obtained in air-equilibrated solution. The binding properties of the investigated ruthenium complex to human serum albumin have been studied and the apparent binding constant for the formation of the protein-ruthenium adduct was determined to be 1.1×10(5)M(-1). The quantum yield and the average lifetime of emission are greatly enhanced upon binding of ruthenium compound to the protein. The DNA binding studies revealed two distinguished binding modes which lead to a decrease in luminescence intensity of ruthenium complex up to 60% for [DNA]/[Ru]<2, and enhancement of emission for [DNA]/[Ru]>80. Preliminary biological studies confirmed fast and efficient accumulation of the ruthenium complex inside cells. Furthermore, the ruthenium complex was found to be relatively cytotoxic with LD50 of 12 and 13 μM for A549 and CT26 cell lines, respectively, under normoxic conditions. The retention and cellular uptake of ruthenium complex is enhanced under hypoxic conditions and its LD50 decreases to 8 μM for A549 cell line.
authors.affiliation: Department of Inorganic Chemistry, Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland.
authors.forename: Olga
authors.initials: O
authors.lastname: Mazuryk
authors.affiliation: Department of Inorganic Chemistry, Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland; Institut of Organic and Analytical Chemistry, University of Orléans, UMR-CNRS 7311, rue de Chartres, BP 6759, 45067 Orléans Cedex 2, France.
authors.forename: Monika
authors.initials: M
authors.lastname: Maciuszek
authors.affiliation: Department of Inorganic Chemistry, Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland.
authors.forename: Grażyna
authors.initials: G
authors.lastname: Stochel
authors.affiliation: Institut of Organic and Analytical Chemistry, University of Orléans, UMR-CNRS 7311, rue de Chartres, BP 6759, 45067 Orléans Cedex 2, France. Electronic address: franck.suzenet@univ-orleans.fr.
authors.forename: Franck
authors.initials: F
authors.lastname: Suzenet
authors.affiliation: Department of Inorganic Chemistry, Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland. Electronic address: brindell@chemia.uj.edu.pl.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Brindell
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008163:Luminescent Measurements; D051379:Mice; D057054:Molecular Imaging / Q000379:methods; D009593:Nitroimidazoles / Q000737:chemistry*; D011485:Protein Binding; D011725:Pyridines / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D009593:Nitroimidazoles; D011725:Pyridines; D012709:Serum Albumin; D012428:Ruthenium
keywords: Cytotoxicity; DNA; Luminescence; Optical imaging; Ruthenium polypyridyl complex; Theranostic