Abstract
<jats:p>A new macrocyclic ligand, 3-thia-7-aza-1,5(2,6)-dipyridinacyclooctaphane, has been synthesized and functionalized to produce a family of nitrogen/sulfur–based chelators with tunable donor environments. Alkyl and picolyl derivatives were obtained through selective Nalkylation of the secondary amine site with methyl, isopropyl, and picolyl substituents, a tridentate macrocyclic NNS analog was also prepared by N-deletion. The coordination chemistry of these ligands toward Cu(II) and Cu(I) was investigated, and the copper complexes were characterized using X-ray crystallography, UV–vis, cyclic voltammetry (CV), EPR or NMR, and elemental analysis (EA). Acidity constants and metal complex stability constants were determined by UVvis spectrophotometric titrations, providing insight into the ligands’ coordination ability. Radiolabeling with 64Cu revealed that while the isopropyl-functionalized complex exhibited moderate radiolabeling efficiency, the picolyl analog achieved quantitative 64Cu incorporation, underscoring its potential for PET imaging applications.</jats:p>