1,4,7-Triazacyclononane: An effective chelator for copper-64

1,4,7-Triazacyclononane (TACN) is a versatile platform from which various ligands can be derived to form effective chelators for (radio)copper(II) complexation. [1] The ability of TACN-derivatives to form highly stable complexes with copper(II) is greatly influenced by the number and type of substituents on the macrocyclic ring. The formed copper(II) complexes show a broad variability in their thermodynamic stability and kinetic inertness, varying in structure from square-pyramidal to distorted octahedral. TACN-based BFCAs have also been used for indirect radiolabelling of biomolecules, rendering them suitable for imaging and therapy.
Herein, examples of various copper-64 TACN complexes will be presented which provide a picture of how different substituents influence the coordination mode, electronic properties and in vivo stability of. By applying principles of coordination chemistry, it is possible to tune the affinity of TACN-based ligands for copper ligation, as well as their availability for subsequent biomolecular functionalisation. Target-specific TACN based conjugates (peptides, antibody fragments) and bio(nano)materials labelled with copper-64 enabling tumour imaging and biodistribution studies via positron emission tomography will be discussed as well. [2, 3, 4]

[1] T. Joshi et al. ChemPlusChem 2018; DOI: 10.100 2/cplu.201800103.
[2] K. Pant et al. Bioconjugate Chem. 2015; 26: 906-918.
[3] K. Viehweger et al. Bioconjugate Chem. 2014; 25: 1011-1022.
[4] R. Bergmann et al. Sci. Rep. 2017; 7.