Development of new radiopharmaceuticals based on rhenium-188 depends on finding appropriateligands able to give complexes with high in vivo stability. Rhenium(III) mixed-ligand complexes withtetradentate/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 amongthe promising tools to achieve this goal. According to this approach, we synthesized and characterizeda series of rhenium model complexes. In vitro stabilities of the corresponding rhenium-188 complexeswere determined by incubating 2-3 MBq or alternatively 37 MBq of the complexes in phosphatebuffer, human plasma, and rat plasma, respectively, at 22
C or 37
C, followed by checking the amountof
188ReO
4- formed after 1 h, 24, and 48 h by thin-layer chromatography. The rate of perrhenateformation varied over a wide range, depending primarily on the nature of the phosphorus(III) ligand.Physicochemical parameters of the corresponding nonradioactive rhenium complexes were analyzedin detail to find out the factors influencing their different stability and furthermore to design newsubstitution-inert '4 + 1' complexes. Tolman's cone angle of phosphorus(III) ligands and the lipophiliccharacter 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 thesecompounds were selected from electronic spectra (wavelength of the Re
S charge-transfer band),cyclovoltammetric measurements (
E of the Re
III/Re
IV couple), and NMR investigations (
31P chemicalshift of coordinated P(III) ligands).