Carbohydrate-Appended 2,2‘-Dipicolylamine Metal Complexes as Potential Imaging Agents

Abstract

Three discrete carbohydrate-appended 2,2'-dipicolylamine ligands were complexed to the {M(CO)(3)}(+) (M = (99m)Tc/Re) core: 2-(bis(2-pyridinylmethyl)amino)ethyl-beta-d-glucopyranoside (L(1)()), 2-(bis(2-pyridinylmethyl)amino)ethyl-beta-D-xylopyranoside (L(2)()), and 2-(bis(2-pyridinylmethyl)amino)ethyl-alpha-d-mannopyranoside (L(3)). An ethylene spacer is used to separate the carbohydrate moiety and the dipicolylamine (DPA) function in all three ligands. The Re complexes [Re(L(1-3))(CO)(3)]Br were characterized by (1)H and (13)C 1D/2D NMR spectroscopies, which confirmed the pendant nature of the carbohydrate moieties in solution. NMR measurements also established the long-range asymmetric effect of the carbohydrate functions on the chelating portion of the ligand. One analogue, [Re(L(1))(CO)(3)]Cl, was characterized in the solid state by X-ray crystallography. Further characterization was provided by IR spectroscopy, elemental analysis, conductivity, and mass spectrometry. Radiolabeling of L(1)-L(3) with [(99m)Tc(H(2)O)(3)(CO)(3)](+) afforded high yield compounds of identical character to the Re analogues. The radiolabeled compounds were found to be stable toward ligand exchange in the presence of a large excess of either cysteine or histidine over a 24-h period.