Kinetic inertness and electrochemical behavior of copper(II) tetraazamacrocyclic complexes: Possible implications for in vivo stability

The kinetic inertness of copper(II) complexes of several carboxymethyl-armed cyclams and cyclens in 5 m HCl have been determined confirming that the complex derived from crossbridged cyclam. (Cu-CB-TE2A) is by far the most resistant to acid decomplexation. FT-IR studies in D2O solution revealed its unique resistance to full carboxylate protonation and its retention of coordination by both pendant arms even in I m DCl. The X-ray structure of its monoprotonated form, [CuCB-TE2AH](+), also established full coordination by both COO- and COOH pendant arms in the solid state. Cyclic voltammograms of four carboxymethyl pendant-armed cyclam and cyclen complexes in aqueous solution were obtained with only Cu-CB-TE2A displaying a quasi-reversible Cur(II)/ Cu-I reduction wave. These indicators correlate with the superior in vivo behavior of this complex and its bifunctional conjugate. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005).