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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Mixed-ligand rhenium-188 complexes with tetradentate/monodentate NS3/P ('4 + 1') coordination: relation of structure with antioxidation stability.

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).[1]

References

  1. Mixed-ligand rhenium-188 complexes with tetradentate/monodentate NS3/P ('4 + 1') coordination: relation of structure with antioxidation stability. Schiller, E., Seifert, S., Tisato, F., Refosco, F., Kraus, W., Spies, H., Pietzsch, H.J. Bioconjug. Chem. (2005) [Pubmed]
 
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