Macrocyclic diamide ligand systems: potential chelators for 64Cu- and 68Ga-based positron emission tomography imaging agents.
The N(4)-macrocyclic ligand 2,10-dioxo-1,4,8,11-tetraazabicyclo[11.4.0]1,12-heptadeca-1(12),14,16-triene H(2)L has been synthesized by the [1 + 1] condensation reaction between 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). H(2)L 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 H(2)O. 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 (64)Cu. In vivo biodistribution studies for the (64)Cu labeled complex, (64)Cu-1, in male Lewis rats, showed that the activity is cleared rapidly from the blood within 1-2 h post-administration.
Barnard
Peter J
PJ
Department of Chemistry, Inorganic Chemistry Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QR, UK. p.barnard@latrobe.edu.au
Holland
Jason P
JP
Bayly
Simon R
SR
Wadas
Thaddeus J
TJ
Anderson
Carolyn J
CJ
Dilworth
Jonathan R
JR
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D002614:Chelating Agents / Q000737:chemistry*; D003301:Copper Radioisotopes / Q000737:chemistry; D018360:Crystallography, X-Ray; D055664:Electrochemical Techniques; D005710:Gallium Radioisotopes / Q000737:chemistry; D008024:Ligands; D047028:Macrocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D049268:Positron-Emission Tomography; D051381:Rats; D011917:Rats, Inbred Lew
C519942:2,10-dioxo-1,4,8,11-tetraazabicyclo(11.4.0)1,12-heptadeca-1(12),14,16-triene; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002614:Chelating Agents; D003301:Copper Radioisotopes; D005710:Gallium Radioisotopes; D008024:Ligands; D047028:Macrocyclic Compounds