Cyclam Derivatives with a Bis(phosphinate) or a Phosphinato-Phosphonate Pendant Arm: Ligands for Fast and Efficient Copper(II) Complexation for Nuclear Medical Applications
| Autoři | |
|---|---|
| Rok publikování | 2015 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Inorganic Chemistry |
| Fakulta / Pracoviště MU | |
| Citace | |
| www | http://pubs.acs.org/doi/full/10.1021/acs.inorgchem.5b01791 |
| Doi | http://dx.doi.org/10.1021/acs.inorgchem.5b01791 |
| Obor | Anorganická chemie |
| Klíčová slova | MACROCYCLIC CHELATORS; POSITRON-EMISSION-TOMOGRAPHY; COORDINATION PROPERTIES; METAL-IONS; BIFUNCTIONAL CHELATOR |
| Popis | Cyclam derivatives bearing one geminal bis(phosphinic acid), (H2L1), or phosphinic-phosphonic acid, (H3L2), pendant arm were synthesized and studied as potential copper(II) chelators for nuclear medical applications. The ligands showed good selectivity for copper(II) over zinc(II) and nickel(II) ions. Kinetic study revealed an unusual threestep complex formation mechanism. The initial equilibrium step leads to out-of-cage complexes with Cu2+ bound by the phosphorus-containing pendant arm. These species quickly rearrange to an in-cage complex with cyclam conformation II, which isomerizes to another in-cage complex with cyclam conformation I. The first in-cage complex is quantitatively formed in seconds (pH approximate to 5, 25 degrees C, Cu:L = 1:1, c(M) approximate to 1 mM). At pH >12, I isomers undergo nitrogen atom inversion, leading to III isomers; the structure of the III-[Cu(HL2)] complex in the solid state was confirmed by X-ray diffraction analysis. In an alkaline solution, interconversion of the I and III isomers is mutual, leading to the same equilibrium isomeric mixture; such behavior has been observed here for the first time for copper(II) complexes of cyclam derivatives. Quantum-chemical calculations showed small energetic differences between the isomeric complexes of H3L2 compared with analogous data for isomeric complexes of cyclam derivatives with one or two methylphosphonic acid pendant arm(s). Acid-assisted dissociation proved the kinetic inertness of the complexes. Preliminary radiolabeling of H2L1 and H3L2 with Cu-64 was fast and efficient, even at room temperature. The rare combination of simple ligand synthesis, very fast copper(II) complex formation, high thermodynamic stability, kinetic inertness, efficient radiolabeling, and expected low bone tissue affinity makes such ligands suitably predisposed to serve as chelators of copper radioisotopes in nuclear medicine. |
| Související projekty: |