title: Investigation of the binding of cis/trans-[MCl4(1H-indazole)(NO)](-) (M = Ru, Os) complexes to human serum albumin.
abstract: Overall binding affinity of sodium or indazolium cis/trans-[MCl4(1H-indazole)(NO)] (M = Ru, Os) complexes towards human serum albumin (HSA) and high molecular mass components of the blood serum was monitored by ultrafiltration. HSA was found to be mainly responsible for the binding of the studied ruthenium and osmium complexes. In other words, this protein can provide a depot for the compounds and can affect their biodistribution and transport processes. In order to elucidate the HSA binding sites tryptophan fluorescence quenching studies and displacement reactions with the established site markers warfarin and dansylglycine were performed. Conditional stability constants for the binding to sites I and II on HSA were computed showing that the studied ruthenium and osmium complexes are able to bind into both sites with moderately strong affinity (logK' = 4.4-5.1). Site I is slightly more favored over site II for all complexes. No significant differences in the HSA binding properties were found for these metal complexes demonstrating negligible influence of the type of counterion (sodium vs indazolium), the metal ion center identity (Ru vs. Os) or the position of the nitrosyl group on the binding event. Electron paramagnetic resonance spin labeling of HSA revealed that indazolium trans-[RuCl4(1H-indazole)(NO)] and long-chain fatty acids show competitive binding to HSA. Moreover, this complex has a higher affinity for site I, but when present in excess, it is able to bind to site II as well, and displace fatty acids.
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary; MTA-SZTE Bioinorganic Chemistry Research Group, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Dömötör
authors.affiliation: University of Vienna, Institute of Inorganic Chemistry, Währinger Strasse 42, A-1090, Vienna, Austria.
authors.forename: Anna
authors.initials: A
authors.lastname: Rathgeb
authors.affiliation: University of Vienna, Institute of Inorganic Chemistry, Währinger Strasse 42, A-1090, Vienna, Austria.
authors.forename: Paul-Steffen
authors.initials: PS
authors.lastname: Kuhn
authors.affiliation: EPR laboratory, Faculty of Physical Chemistry, University of Belgrade, Studentski trg 12-16, 11158, Belgrade, Serbia. Electronic address: ana@ffh.bg.ac.rs.
authors.forename: Ana
authors.initials: A
authors.lastname: Popović-Bijelić
authors.affiliation: EPR laboratory, Faculty of Physical Chemistry, University of Belgrade, Studentski trg 12-16, 11158, Belgrade, Serbia.
authors.forename: Goran
authors.initials: G
authors.lastname: Bačić
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary. Electronic address: enyedy@chem.u-szeged.hu.
authors.forename: Eva Anna
authors.initials: EA
authors.lastname: Enyedy
authors.affiliation: University of Vienna, Institute of Inorganic Chemistry, Währinger Strasse 42, A-1090, Vienna, Austria. Electronic address: vladimir.arion@univie.ac.at.
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Arion
mesh_terms: D006801:Humans; D007191:Indazoles / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D009992:Osmium / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry*
chemical_list: D007191:Indazoles; D009942:Organometallic Compounds; D012709:Serum Albumin; D009992:Osmium; D012428:Ruthenium
keywords: Albumin binding; Antitumor activity; EPR spin labeling; Fluorometry; Nitrosyl