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Macrocyclic Diamide Ligand Systems: Potential Chelators for Cu-64- and Ga-68-Based Positron Emission Tomography Imaging Agents
Journal article   Open access   Peer reviewed

Macrocyclic Diamide Ligand Systems: Potential Chelators for Cu-64- and Ga-68-Based Positron Emission Tomography Imaging Agents

Peter J. Barnard, Jason P. Holland, Simon R. Bayly, Thaddeus J. Wadas, Carolyn J. Anderson and Jonathan R. Dilworth
Inorganic chemistry, Vol.48(15), pp.7117-7126
08/03/2009
DOI: 10.1021/ic900307f
PMCID: PMC4287963
PMID: 19588930
url
https://www.ncbi.nlm.nih.gov/pmc/articles/4287963View
Open Access

Abstract

The N-4-macrocyclic ligand 2,10-dioxo-1,4,8,11-tetraazabicyclo[11,4.0]1,12-heptadeca-1(12),14,16-triene H2L has been synthesized by the [1 + 1]condensation reactionbetween N,N'-bis(chloroacetyl)-1,2-phenylenediamine and 1,3-propylenediamine. The coordination chemistry of this ligand has been investigated with the metal ions Cu (II), Ni(II), Zn(II), and Ga(III) (complexes 1, 2, 3 and 4, respectively). H2L and its metal complexes have been fully characterized by the use of NMR, UV/vis, electron paramagnetic resonance, and elemental analysis where appropriate. The four metal complexes 1-4 have been structurally characterized by X-ray crystallography which confirmed that in all cases the amide nitrogen atoms are deprotonated and coordinated to the metal center. Complexes 3 and 4 are five-coordinate with a water molecule and chloride ion occupying the apical site, respectively. Cyclic voltammetric measurements on complex 1 show that this complex is oxidized reversibly with a half-wave potential, E-1/2 = 0.47 V, and reduced irreversibly at E-P = - 1.84 V. Density functional theory calculations reproduce the geometries of the four complexes. The one-electron reduction and oxidation potentials for 1 were calculated by using two solvent models, DMF and H2O. The calculations indicated that the one electron oxidation of 1 may involve removal of an electron from the ligand as opposed to the metal center, producing a diradical. The diamide macrocyle is of interest for the development of new positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging agents, and a radiolabeled complex has been synthesized with the positron emitting isotope (CU)-C-64. In vivo biodistribution studies for the Cu-64 labeled complex, C-64-1, in male Lewis rats, showed that the activity is cleared rapidly from the blood within 1-2 h post-administration.
 Chemistry Chemistry, Inorganic & Nuclear Physical Sciences Science & Technology

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