title: Interaction of apo-transferrin with anticancer ruthenium complexes NAMI-A and its reduced form.
abstract: NAMI-A i.e. (ImH)[trans-RuCl(4)(DMSO)(Im)] (where Im is imidazole) is a ruthenium(III) complex with promising antimetastatic activity, which has been classified for II phase clinical trial. In this study, its binding properties toward apo-transferrin (apo-Tf) with regard to its hydrolytic and redox behavior are systematically investigated by the use of fluorescence spectroscopy. The reaction of NAMI-A and its reduced form with apo-Tf is proceeded by formation of aqua derivatives and the presence of at least one labile aqua ligand is sufficient to form adducts. It is found that presence of bicarbonate is not necessary for interaction of studied ruthenium complexes with apo-Tf. The calculated association constants for both NAMI-A and its reduced form are very similar with the values of 1.28 × 10(4)M(-1) and 1.36 × 10(4)M(-1) at 37 °C, respectively however, the reduced derivatives reach the equilibrium ca. 8-10 times slower. The percentage of ruthenium content in protein fractions separated from protein-unbounded ruthenium by using FPLC (fast protein liquid chromatography) method is rather high and depends on redox state of the complex, for most samples is found higher for reduced species.
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.forename: Katarzyna
authors.initials: K
authors.lastname: Kurpiewska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Lewiński
authors.forename: Grażyna
authors.initials: G
authors.lastname: Stochel
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Brindell
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D002853:Chromatography, Liquid; D004121:Dimethyl Sulfoxide / Q000031:analogs & derivatives* / Q000737:chemistry; D006868:Hydrolysis; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D017975:Ruthenium Compounds; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D014168:Transferrin / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; D014168:Transferrin; C113661:imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III); D004121:Dimethyl Sulfoxide