Search

In the last two decades, a number of chelate strategies have been proposed for the fac-[MI(CO)3]+ (M = Re, 99mTc) core in radiopharmaceutical applications. However, the development of new ligands/complexes with improved function and in vivo performance has been limited in recent years. Expanding on our previous studies using the 2 + 1 labeling strategy, a series of bidentate ligands (neutral vs. anionic) containing an aromatic amine in combination with monodentate pyridine analogs or imidazole were explored to determine the influence of the bidentate and monodentate ligands on the formation and stability of the respective complexes. The 2 + 1 complexes with Re and 99mTc were synthesized in two steps and characterized by standard radio/chemical methods. X-ray characterization and density functional theory analysis of the Re 2 + 1 complexes with the complete bidentate series with 4-dimethylaminopyridine were conducted, indicating enhanced ligand binding energies of the neutral over anionic ligands. In the 99mTc studies, anionic bidentate ligands had significantly higher formation yields of the 2 + 1 product, but neutral ligands appear to have increased stability in an amino acid challenge assay. Both bidentate series exhibited improved stability by increasing the basicity of the pyridine ligands. [ABSTRACT FROM AUTHOR]

Rhodium remains a high value platinum group metal that has key applications in electronics, catalysts, and batteries. To provide a useful tool for Rh isolation, a novel tridentate ligand utilizing soft N and S donors was designed to specifically extract Rh. The synthesis, complexation kinetics, and liquid–liquid extraction studies were performed to explore the overall process and recovery of Rh from chloride media. [ABSTRACT FROM AUTHOR]

The viability of the Huisgen cydoaddition reaction for clickable radiopharmaceutical probes was explored with an alkyne-functionalized 2r[(pyridin-2-ylmethy3)amino]-acetic acid (PMAA) ligand system, 3, and fac-[M¹(OH2)3(CO)3]+ (M = Re, 99mTc). Two synthetic strategies, (1) click, then chelate and (2) chelate, then dick, were investigated to determine the impact of assembly order on the reactivity of the system. In the click, then chelate approach, fac-[M¹(OH2)3(CO)3]+ was reacted with the PMAA hgand "clicked" to the benzyl azide, 5, to yidd two unique coordination species, fac-M¹(CO)3(O,Namine,Npy-5)], M = Re (8), 99mTc (8A), and fac-[M¹(CO)3(Ntn,Namine,Npy-5)], M = Re (9), 99mTc (9A), where coordination is through the triazole (Ntn), central amine (Namine), pyridine (Npy), or carboxylate (O). Depending on the reaction pH, different ratios of complexes 8(A) and 9(A) were observed, but single species were obtained of (O,Namine,Npy) coordination, 8(A), in basic pFls (>9) and (Ntn,Namine,Npy) coordination, 9(A), in slightly aadic pHs (<4). In the chelate, then click approach, the (O,NamineNpy) coordination of [M¹(CO)3] was preorganized in the alkyne-functionalized fac-[M1(CO)3(O,Namine,Npy-3)], M = Re (6), 99mTc (6A), followed by standard Cu¹-catalyzed Huisgen 'click" conditions at pH ≈ 7.4, where the (O,Namine,Npy) coordination mode remained unchanged upon formation of the triazole product in the clicked molecule. Despite the slow substitution kinetics of the low-spin d6 metal, the coordination modes (O,Namine,Npy) and (Ntn,Namine,Npy)were found to reversiWy intraconvert between 8(A) and 9(A) based upon changes in pH that mirrored die (O,Namine,Npy) coordination in basic pHs and (Ntn,Namine,Npy) coordination in acidic pHs. Comparison of the Re and 99mTc analogs also revealed faster intraconversion between the coordination modes for 99mTc [ABSTRACT FROM AUTHOR]

Isoxazole ring formation was examined as a potential Cu-free alternative click reaction to CuI-catalyzed alkyne/azide cycloaddition. The isoxazole reaction was explored at macroscopic and radiotracer concentrations with the fac-[MI(CO)3]+ (M = Re, 99mTc) core for use as a noncoordinating linker strategy between covalently linked molecules. Two click assembly methods (click, then chelate and chelate, then click) were examined to determine the feasibility of isoxazole ring formation with either alkyne-functionalized tridentate chelates or their respective fac-[MI(CO)3]+ complexes with a model nitrile oxide generator. Macroscale experiments, alkyne-functionalized chelates, or Re complexes indicate facile formation of the isoxazole ring. 99mTc experiments demonstrate efficient radiolabeling with click, then chelate; however, the chelate, then click approach led to faster product formation, but lower yields compared to the Re analogues. [ABSTRACT FROM AUTHOR]