Complexes of orotic acid and derivatives with the fac-[M(CO)3]+ (M = Re and 99Tc/99mTc) core as radiopharmaceutical probes

Abstract

We report the aqueous synthesis of complexes of orotic acid (H2oa) and derivatives (5-fluoroorotic acid (H2foa) and 5-aminoorotic acid (H2aoa)) with the organometallic fac-[M(CO)3]+ (M = Re and 99Tc/99mTc) moiety. Complexes [Re(CO)3(OH2)(oa)]- (1) and [99mTc(CO)3(OH2)(oa)]- (2) were obtained with H2oa in water from [Re(CO)5Br] and [99mTc(CO)3(OH2)3]+ respectively. Complexes [M(CO)3(OH2)(foa)]- (M = Re (3), 99mTc (4)) were obtained as for the synthesis of 1 and 2. The structural identities of complexes 1–4 were confirmed by coinjection in the HPLC by UV/Vis detection coupled with a γ-detector. Complex [99Tc(CO)3(OH2)(foa)]- (5) was obtained from [99TcCl3(CO)3]2- and H2foa in water. The structures of 3 and 5 were elucidated by single crystal X-ray crystallography. Coinjection of 4 and 5 assessed the identity of the respective 99mTc complex. The reaction of 5-aminoorotic acid (H2aoa) with [Re(CO)5Br] in water resulted in the ligand-bridged dimeric complex [(Re(µ-aoa)(CO)3]22– (6). The reaction of H2aoa with [99mTc(CO)3(OH2)3]+ in water led to the monomeric 99mTc complex only.