Triamidetriamine bearing macrobicyclic and macrotricyclic ligands: potential applications in the development of copper-64 radiopharmaceuticals
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Date
2013-12-16
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Publisher
American Chemical Society
Abstract
A versatile and straightforward synthetic approach is described for the preparation of triamide bearing analogues of sarcophagine hexaazamacrobicyclic cage ligands without the need for a templating metal ion. Reaction of 1,1,1-tris(aminoethyl)ethane (tame) with 3 equiv of 2-chloroacetyl chloride, yields the tris(α-chloroamide) synthetic intermediate 6, which when treated with either 1,1,1-tris(aminoethyl)ethane or 1,4,7-triazacyclononane furnished two novel triamidetriamine cryptand ligands (7 and 8 respectively). The Co(III) and Cu(II) complexes of cryptand 7 were prepared; however, cryptand 8 could not be metalated. The cryptands and the Co(III) complex 9 have been characterized by elemental analysis, 1H and 13C NMR spectroscopy, and X-ray crystallography. These studies confirm that the Co(III) complex 9 adopts an octahedral geometry with three facial deprotonated amido-donors and three facial amine donor groups. The Cu(II) complex 10 was characterized by elemental analysis, single crystal X-ray crystallography, cyclic voltammetry, and UV–visible absorption spectroscopy. In contrast to the Co(III) complex (9), the Cu(II) center adopts a square planar coordination geometry, with two amine and two deprotonated amido donor groups. Compound 10 exhibited a quasi-reversible, one-electron oxidation, which is assigned to the Cu2+/3+ redox couple. These cryptands represent interesting ligands for radiopharmaceutical applications, and 7 has been labeled with 64Cu to give 64Cu-10. This complex showed good stability when subjected to l-cysteine challenge whereas low levels of decomplexation were evident in the presence of l-histidine. © 2013 American Chemical Society
Description
Keywords
Ligands, Copper 64, Radiopharmaceuticals, Synthesis, Amino acids, Cysteine, Histidine, Crystallography
Citation
Tan, K. V., Pellegrini, P. A., Skelton, B. W., Hogan, C. F., Greguric, I., & Barnard, P. J. (2014). Triamidetriamine Bearing Macrobicyclic and Macrotricyclic Ligands: Potential Applications in the Development of Copper-64 Radiopharmaceuticals. Inorganic Chemistry, 53(1), 468-477. doi:10.1021/ic4024508