Imidazole-Based [2+1] Re(I)/99mTc(I) Complexes as Isostructural Nuclear and Optical Probes

The synthesis, stability, and photophysical properties of [2 + 1] Re(I)/Tc(I) complexes derived from bipyridine and a series of imidazole derivatives were investigated as a means of identifying complexes suitable for creating targeted isostructural optical/nuclear molecular imaging probes. To prepare the desired complexes, [Re(CO)(3)(H2O)(3)]Br was combined with 2,2'-bipyridine (bipy) to give [Re(CO)(3)(bipy)Br], which in turn was converted to the desired complexes by treatment with functionalized imidazoles, yielding crystal structures of two new Re complexes. The corresponding Tc-99m complexes [Tc-99m(CO)(3)(bipy)(L)](+) (L = imidazole derivatives) were prepared by combining [Tc-99m(CO)(3)(bipy)((HO)-O-2)]Cl with the same series of ligands and heating at 40 or 60 degrees C for 30 min. Quantitative transformation to the final products was confirmed in all cases by HPLC, and the nature of the complexes was verified by comparison to the authentic Re standards. Incubation in saline and plasma, and amino acid challenge experiments showed that N-substituted imidazole derivatives, bearing electron donating groups, exhibited superior stability to analogous metal complexes derived from less basic ligands. Imaging studies in mice revealed that with the appropriate choice of monodentate ligand, it is possible to prepare robust [2 + 1] Tc complexes that can be used as the basis for preparing targeted isostructural optical and nuclear probes.