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 cross‐bridged cyclam (Cu‐CB‐TE2A) is by far the most resistant to acid decomplexation. FT‐IR studies in D 2 O solution revealed its unique resistance to full carboxylate protonation and its retention of coordination by both pendant arms even in 1 M DCl. The X‐ray structure of its monoprotonated form, [Cu‐CB‐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 Cu II /Cu I reduction wave. These indicators correlate with the superior in vivo behavior of this complex and its bifunctional conjugate. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)