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

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-methoxybenzylthio)propionic acid 1 was effected via reaction with (NEt4)(2)[ReBr3(CO)(3)] in the presence of NaHCO3. Complex Re-1 crystallized from methanol/water and its structure was established by IR, H-1 and C-13 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)(3)Br] Re-2. At the tracer level, the analogous complexes fac-[Tc-99m(NSO)(CO)(3)], Tc-99m-1 and fac-[Re-188(NSO)(CO)(3)], Re-188-1, were synthesized and their radiochemical stability in physiological conditions was determined. Both tracer complexes Tc-99m-1 and Re-188-1 are stable in solution as well as in the presence of strongly coordinating agents like histidine or cysteine. (C) 2011 Elsevier B.V. All rights reserved.