NOTA Complexes with Copper(II) and Divalent Metal Ions: Kinetic and Thermodynamic Studies

Warning

This publication doesn't include Faculty of Arts. It includes Faculty of Science. Official publication website can be found on muni.cz.
Authors

KUBICEK Vojtěch BOHMOVA Zuzana ŠEVČÍKOVÁ Romana VANĚK Jakub LUBAL Přemysl POLAKOVA Zuzana MICHALICOVÁ Romana KOTEK Jan HERMANN Petr

Year of publication 2018
Type Article in Periodical
Magazine / Source Inorganic Chemistry
MU Faculty or unit

Faculty of Science

Citation
Web http://dx.doi.org/10.1021/acs.inorgchem.7b02929
Doi http://dx.doi.org/10.1021/acs.inorgchem.7b02929
Keywords MACROCYCLIC CHELATORS; BIFUNCTIONAL CHELATOR; TRIAZACYCLONONANE-TRIACETIC ACID; FORMATION AND DISSOCIATION KINETICS
Description H(3)nota derivatives are among the most studied macrocyclic ligands and are widely used for metal ion binding in biology and medicine. Despite more than 40 years of chemical research on H(3)nota, the comprehensive study of its solution chemistry has been overlooked. Thus, the coordination behavior of H(3)nota with several divalent metal ions was studied in detail with respect to its application as a chelator for copper radioisotopes in medical imaging and therapy. In the solid-state structure of the free ligand in zwitterionic form, one proton is bound in the macrocyclic cavity through a strong intramolecular hydrogen-bond system supporting the high basicity of the ring amine groups (log K-a = 13.17). The high stability of the [Cu(nota)](-) complex (log K-ML = 23.33) results in quantitative complex formation, even at pH <1.5. The ligand is moderately selective for Cu(II) over other metal ions (e.g., log K-ML(Zn) = 22.32 and log K-ML(Ni) = 19.24). This ligand forms a more stable complex with Mg(II) than with Ca(II) and forms surprisingly stable complexes with alkali-metal ions (stability order Li(I) > Na(I) > K(I)). Thus, H(3)nota shows high selectivity for small metal ions. The [Cu(nota)](-) complex is hexacoordinated at neutral pH, and the equatorial N2O2 interaction is strengthened by complex protonation. Detailed kinetic studies showed that the Cu(II) complex is formed quickly (millisecond time scale at c(Cu) approximate to 0.1 mM) through an out-of-cage intermediate. Conversely, conductivity measurements revealed that the Zn(II) complex is formed much more slowly than the Cu(II) complex. The Cu(II) complex has medium kinetic inertness (tau(1/2) 46 s; pH 0, 25 degrees C) and is less resistant to acid-assisted decomplexation than Cu(II) complexes with H(4)dota and H(4)teta. Surprisingly, [Cu(nota)](-) decomplexation is decelerated in the presence of Zn(II) ions due to the formation of a stable dinuclear complex. In conclusion, H(3)nota is a good carrier of copper radionuclides because the [Cu(nota)](-) complex is predominantly formed over complexes with common impurities in radiochemical formulations, Zn(II) and Ni(II), for thermodynamic and, primarily, for kinetic reasons. Furthermore, the in vivo stability of the [Cu(nota)](-) complex may be increased due to the formation of dinuclear complexes when it interacts with biometals.
Related projects:

You are running an old browser version. We recommend updating your browser to its latest version.