A new [2+1] mixed ligand concept based on [99(m)Tc(OH2)3(CO)3]+:: a basic study

Mixed ligand fac-tricarbonyl complexes of the general formula [M(L-1)(L-2)(CO)(3)] (M = Re, Tc-99(m), L-1 = imidazole, benzyl isocyanide, L-2 = 1H-imidazole-4-carboxylic acid, pyridine-2,4-dicarboxylic acid, pyridine-2,5-dicarboxylic acid) have been prepared starting from the precursors [M(OH2)(3)(CO)(3)](+). The complexes can be obtained in good yield and purity in a two-step procedure by first attaching the bidentate ligand followed by addition of the monodentate. Tc-99m compounds can also be prepared at the tracer level in one-pot procedures with L-1 and L-2 being concomitantly present. This [2 + 1] approach allows the labeling of bioactive molecules containing a monodentate or a bidentate donor site. Examples given in here are N-(tert-butoxycarbonyl)glycyl-N(3-(imidazol- 1-yl)propyl)phenylalaninamide, 5-((3-(imidazol-1-yl)propyl)aminomethyl)-2'-deoxyuridine and 4-(5-isonitrilpentyl)-1-(2-methoxyphenyl)-piperazine as L-1 and N-((6-carboxypyridine-3-yl)methyl)glycylphenyl-alanine as L-2. The corresponding second ligand can be used to influence the physico-chemical properties of the conjugate. The crystal structures of [Tc-99(OH2)(imc)(CO)(3)], [Re(OH2)(2,4-dipic)(CO)(3)], [Re(bic)(2,4-dipic)(CO)(3)] and [Re(im)(2,5-dipic)(CO)(3)] are reported.