American Chemical Society
ic502520x_si_002.cif (2.81 MB)

Influence of Functionalized Pyridine Ligands on the Radio/Chemical Behavior of [MI(CO)3]+ (M = Re and 99mTc) 2 + 1 Complexes

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posted on 2015-02-16, 00:00 authored by Thomas R. Hayes, Patrice A. Lyon, Charles L. Barnes, Steven Trabue, Paul D. Benny
While a number of chelate strategies have been developed for the organometallic precursor fac-[MI(OH2)3(CO)3]+ (M = Re, 99mTc), a unique challenge has been to improve the overall function and performance of these complexes for in vivo and in vitro applications. Since its discovery, fac-[MI(OH2)3(CO)3]+ has served as an essential scaffold for the development of new targeted 99mTc based radiopharmaceuticals due to its labile aquo ligands. However, the lipophilic nature of the fac-[MI(CO)3]+ core can influence the in vivo pharmacokinetics and biodistribution of the complexes. In an effort to understand and improve this behavior, monosubstituted pyridine ligands were used to assess the impact of donor nitrogen basicity on binding strength and stability of fac-[MI(CO)3]+ in a 2 + 1 labeling strategy. A series of Re and 99mTc complexes were synthesized with picolinic acid as a bidentate ligand and 4-substituted pyridine ligands. These complexes were designed to probe the effect of pKa from the monodentate pyridine ligand both at the macro scale and radiochemical concentrations. Comparison of X-ray structural data and radiochemical solution experiments clearly indicate an increase in overall yield and stability as pyridine basicity increased.