title: Mixed-ligand rhenium-188 complexes with tetradentate/monodentate NS3/P ('4 + 1') coordination: relation of structure with antioxidation stability.
abstract: Development of new radiopharmaceuticals based on rhenium-188 depends on finding appropriate ligands able to give complexes with high in vivo stability. Rhenium(III) mixed-ligand complexes with tetradentate/monodentate ('4 + 1') coordination of the general formula [Re(NS(3))(PRR'R' ')] (NS(3) = tris(2-mercaptoethyl)amine and derivatives thereof, PRR'R' ' = phosphorus(III) ligands) appear to be among the promising tools to achieve this goal. According to this approach, we synthesized and characterized a series of rhenium model complexes. In vitro stabilities of the corresponding rhenium-188 complexes were determined by incubating 2-3 MBq or alternatively 37 MBq of the complexes in phosphate buffer, human plasma, and rat plasma, respectively, at 22 degrees C or 37 degrees C, followed by checking the amount of (188)ReO(4)(-) formed after 1 h, 24, and 48 h by thin-layer chromatography. The rate of perrhenate formation varied over a wide range, depending primarily on the nature of the phosphorus(III) ligand. Physicochemical parameters of the corresponding nonradioactive rhenium complexes were analyzed in detail to find out the factors influencing their different stability and furthermore to design new substitution-inert '4 + 1' complexes. Tolman's cone angle of phosphorus(III) ligands and the lipophilic character of the inner coordination sphere were found to be crucial factors to build up stable rhenium '4 + 1' complexes. Additional information useful to describe electronic and steric properties of these compounds were selected from electronic spectra (wavelength of the Re-->S charge-transfer band), cyclovoltammetric measurements (E degrees of the Re(III)/Re(IV) couple), and NMR investigations ((31)P chemical shift of coordinated P(III) ligands).
authors.affiliation: Forschungszentrum Rossendorf, Institut für Bioanorganische und Radiopharmazeutische Chemie, 510119, D-01314 Dresden, Germany.
authors.forename: Eik
authors.initials: E
authors.lastname: Schiller
authors.forename: Sepp
authors.initials: S
authors.lastname: Seifert
authors.forename: Francesco
authors.initials: F
authors.lastname: Tisato
authors.forename: Fiorenzo
authors.initials: F
authors.lastname: Refosco
authors.forename: Werner
authors.initials: W
authors.lastname: Kraus
authors.forename: Hartmut
authors.initials: H
authors.lastname: Spies
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Pietzsch
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000737:chemistry; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D011868:Radioisotopes / Q000737:chemistry; D051381:Rats; D012211:Rhenium / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D008024:Ligands; D011868:Radioisotopes; C503265:tris(2-mercaptoethyl)amine phosphorus(III); D003543:Cysteamine; D012211:Rhenium