Histidine derivatives as tridentate chelators for the fac-[M I(CO) 3] (Re, 99mTc, 188Re) core: Synthesis, structural characterization, radiochemistry and stability

Abstract

The development of new rhenium(I)- and technetium(I)–tricarbonyl complexes can lead to potentially useful radiopharmaceuticals. In this work, the synthesis of the neutral rhenium complex fac-[Re(NSO)(CO) 3], Re-1, where NSO is the tridentate chelating agent 3-(1H-imidazol-4-yl)-2-( p-methoxy-benzylthio)propionic acid 1 was effected via reaction with (NEt 4) 2[ReBr 3(CO) 3] in the presence of NaHCO 3. Complex Re-1 crystallized from methanol/water and its structure was established by IR, 1H and 13C NMR spectroscopies, ESI-MS analysis and X-ray crystallography. When the reaction took place in the absence of base, HPLC analysis revealed the presence of a second product (yield 7%) that was assigned by NMR and ESI analysis to be complex fac-[Re(NS)(CO) 3Br] Re-2. At the tracer level, the analogous complexes fac-[ 99mTc(NSO)(CO) 3], 99mTc-1 and fac-[ 188Re(NSO)(CO) 3], 188 Re-1, were synthesized and their radiochemical stability in physiological conditions was determined. Both tracer complexes 99m Tc-1 and 188 Re-1 are stable in solution as well as in the presence of strongly coordinating agents like histidine or cysteine.