Triamidetriamine Bearing Macrobicyclic and Macrotricyclic Ligands: Potential Applications in the Development of Copper-64 Radiopharmaceuticals

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• 作者：Kel Vin Tan ; Paul A. Pellegrini ; Brian W. Skelton ; Conor F. Hogan ; Ivan Greguric ; Peter J. Barnard
• 刊名：Inorganic Chemistry
• 出版年：2014
• 出版时间：January 6, 2014
• 年：2014
• 卷：53
• 期：1
• 页码：468-477
• 全文大小：406K
• ISSN：1520-510X

文摘

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(伪-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鈥搗isible 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 Cu^2+/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.