Abstrakt
NOTA monoamides are commonly and widely used chelators for the complexation of copper radioisotopes applied in molecular imaging and targeted nuclear therapy. However, information about their coordination behavior remains scarce.
In this study, two NOTA-monoamides, N-ethyl (H(2)L1) and N,N-diethyl (H(2)L2), were synthesized as model ligands and tested to probe differences in their coordination behavior between the secondary and tertiary amide pendant arms for potential applications as copper radioisotope carriers. Our results demonstrated that the solid [Cu(L1)] and [Cu(L2)] complex have a distorted octahedral arrangement, similar to structure of the [Cu(Hnota)] complex.
As shown by equilibrium data, the ligands have a slightly lower basicity, and thus complexes with divalent metal ions and Li(I) have slightly lower stability constants than those of the parent ligand, H(3)nota. The dissociation constants of the Cu(II), Zn(II) and Ni(II) complexes with H(2)L1 also indicate deprotonation and N-coordination of the secondary amide group at pH>9.
Complexation of Cu(II) ions with the title ligands is slower than that with H3nota but still very fast (quantitative binding in <1 s, pH 2, millimolar concentrations), and Cu(II) complexes of both monoamide ligands are more resistant to acid-assisted decomplexation than the Cu(II)-H(3)nota complex. Therefore, our coordination data highlight that NOTA-monoamides are suitable chelators for molecular imaging and nuclear medicine.