Synthesis and characterization of rhenium and Technetium-99 m tricarbonyl and dicarbonyl complexes with quinaldic acid and Arsenic/Phosphorus derivatives

The synthesis and characterization of neutral tricarbonyl fac-[Re/^99mTc(quin)(X)(CO)₃] and dicarbonyl cis–trans-[Re/^99mTc(quin)(X)₂(CO)₂] mixed ligand complexes with quinaldic acid (quin) as the bidentate ligand and trimethoxyphosphine [P(OCH₃)₃], tris(hydroxymethyl)-phosphine [P(CH₂OH)₃]_, triphenylphosphine (PPh₃), and triphenylarsine (AsPh₃) as the monodentate ligands (X) is described. The synthesis of the [2 + 1] tricarbonyl complexes proceeds by displacement of the water molecule of the fac-[Re/^99mTc(quin)(H₂O)(CO)₃] by the monodentate ligand. Interestingly, the synthesis of the [2 + 1 + 1] dicarbonyl complexes was achieved only for PPh₃ after replacing the CO group trans to PPh₃ with a second PPh₃ molecule. The latter complex was also obtained by refluxing quinaldic acid with the trans-mer-[Re(PPh₃)₂(Cl)(CO)₃] precursor in toluene. Rhenium complexes were prepared in satisfactory yields and fully characterized. At the technetium-99 m level, complexes were produced in high radiochemical yields and characterized by comparative chromatographic analysis using the analogous rhenium complexes. Complexes have shown varying stability against transchelation by cysteine and histidine in agreement with the decreasing σ-donating capacity of the monodentate ligand (P(OCH₃)₃ > P(CH₂OH)₃ > PPh₃ > AsPh₃. The stable complexes with PPh₃ showed high lipophilicity (LogP 2.90 and 3.10, respectively) due to the lipophilic nature of the monodentate ligands. The σ-donor and π-acceptor capacity of the monodentate ligand strongly influences the formation and stability of the complexes, and these characteristics should be considered before choosing the appropriate ligand for radiopharmaceuticals design.