Aqua-complexes of pyrimidine-4,6-dicarboxylic acid and its monoester with organometallic fac-[M(CO)3]+ (M = Re and 99mTc) core as radiopharmaceutical probes: Synthesis and characterization

Abstract

The current study highlights on the synthesis and characterization of aqua-complexes of the fac-[M(CO)(3)](+) (M = Re and Tc-99m) core with pyrimidine-4,6-dicarboxylic acid (H(2)pmdc) and its monoester 6-(ethoxycarbonyl)pyrimidine-4-carboxylic acid (Hetpmdc), which are the model for future design of imaging and therapeutic radiopharmaceuticals. Complexes [M(CO)(3)(OH2)(Hpmdc)] (M = Re (1) and Tc-99m (2)) were formed from the reaction of H2pmdc with [Re(CO)(5)Br] in water and aqueous solution of [Tc-99m(CO)(3)(OH2)(3)](+) respectively. The reaction of [Re(CO)(5)Br] with H2pmdc in ethanol (EtOH) has also studied and led to the complex [Re(CO)(3)(OH2) (etpmdc)] (3), where etpmdc(-) is 6-(ethoxycarbonyl)pyrimidine-4-carboxylate anion which was formed from the mono-esterification of H2pmdc in parallel with its coordination to the fac-[Re(CO)(3)](+) unit. The complex [Tc-99m (CO)(3)(OH2)(etpmdc)] (4) was formed in parallel with 2 by reacting H2pmdc with aqueous solution of [Tc-99m (CO)(3)(OH2)(3)](+) and ethanol. The chemical identification of 1 and 3 was achieved by using H-1 NMR, C-13 NMR, IR, ESI-MS and elemental analysis. Complex 3 was furtherly identified by using single crystal X-ray crystallography. The structural similarities of 1 and 2 was assessed by coinjection of both complexes in the HPLC with UV/Vis detection coupled with a gamma-detector followed by comparison of retention times of the gamma-peak of 2 and the UV-peak of 1 which allowed unambiguous identification of 2. Similarly, the formation of complex [Tc-99m(CO)(3)(OH2) (etpmdc)] (4) in parallel with 2 was assessed by coinjection of complexes 1 and 3 with the product from the reaction of H2pmdc with aqueous solution of [Tc-99m(CO)(3)(OH2)(3])+ and ethanol in the same HPLC as one used for the structural identification of 2 followed by comparison of retention times of the gamma-peaks of 2 and 4 and the UVpeaks of 1 and 3.