title: Triamidetriamine bearing macrobicyclic and macrotricyclic ligands: potential applications in the development of copper-64 radiopharmaceuticals.
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, (1)H and (13)C 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 Cu(2+/3+) redox couple. These cryptands represent interesting ligands for radiopharmaceutical applications, and 7 has been labeled with (64)Cu to give (64)Cu-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.
authors.affiliation: Department of Chemistry, La Trobe Institute for Molecular Science, La Trobe University , Victoria 3086, Australia.
authors.forename: Kel Vin
authors.initials: KV
authors.lastname: Tan
authors.forename: Paul A
authors.initials: PA
authors.lastname: Pellegrini
authors.forename: Brian W
authors.initials: BW
authors.lastname: Skelton
authors.forename: Conor F
authors.initials: CF
authors.lastname: Hogan
authors.forename: Ivan
authors.initials: I
authors.lastname: Greguric
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Barnard
mesh_terms: D003301:Copper Radioisotopes / Q000737:chemistry* / Q000302:isolation & purification; D018360:Crystallography, X-Ray; D008024:Ligands; D047028:Macrocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification
chemical_list: D003301:Copper Radioisotopes; D008024:Ligands; D047028:Macrocyclic Compounds; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals