title: Influence of functionalized pyridine ligands on the radio/chemical behavior of [M(I)(CO)3](+) (M = Re and (99m)Tc) 2 + 1 complexes.
abstract: While a number of chelate strategies have been developed for the organometallic precursor fac-[M(I)(OH2)3(CO)3](+) (M = Re, (99m)Tc), 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-[M(I)(OH2)3(CO)3](+) has served as an essential scaffold for the development of new targeted (99m)Tc based radiopharmaceuticals due to its labile aquo ligands. However, the lipophilic nature of the fac-[M(I)(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-[M(I)(CO)3](+) in a 2 + 1 labeling strategy. A series of Re and (99m)Tc 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.
authors.affiliation: Department of Chemistry, Washington State University , Pullman, Washington 99164, United States.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Hayes
authors.forename: Patrice A
authors.initials: PA
authors.lastname: Lyon
authors.forename: Charles L
authors.initials: CL
authors.lastname: Barnes
authors.forename: Steven
authors.initials: S
authors.lastname: Trabue
authors.forename: Paul D
authors.initials: PD
authors.lastname: Benny
mesh_terms: D002248:Carbon Monoxide / Q000737:chemistry*; D018360:Crystallography, X-Ray; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D012211:Rhenium / Q000737:chemistry*; D013237:Stereoisomerism; D013667:Technetium / Q000737:chemistry*
chemical_list: D008024:Ligands; D009942:Organometallic Compounds; D011725:Pyridines; D012211:Rhenium; D013667:Technetium; D002248:Carbon Monoxide; C023666:pyridine