Copper(II) and gallium(III) complexes of trans -Bis(2-hydroxybenzyl) cyclen derivatives: Absence of a cross-bridge proves surprisingly more favorable

Two cyclen (1,4,7,10-tetraazacyclododecane) derivatives bearing trans-bis(2-hydroxybenzyl) arms, the 1,7-(2-hydroxybenzyl)-1,4,7,10- tetraazacyclododecane (H₂do2ph) and its cross-bridged counterpart (H₂cb-do2ph), have been synthesized, aiming toward the possible use of their copper(II) and gallium(III) complexes in nuclear medicine. The protonation of both compounds was studied in aqueous solution as well as their complexes with Cu²⁺ and Ga³⁺ cations. The complexes of both ligands with Ca²⁺ and Zn²⁺ metal ions were also studied due to the abundance of these cations in biological media. In mild conditions the complexes of Ca²⁺ and Ga³⁺ with H ₂cb-do2ph did not form. The behavior of the two ligands and their complexes was compared by the values of the equilibrium constants, the data of varied spectroscopic techniques, the values of redox potentials of their copper(II) complexes, and the resistance of the complexes to acid dissociation. It was expected that, as found for related pairs of cyclen and cyclam (1,4,8,11-tetraazacyclotetradecane) derivatives, the cross-bridged macrocyclic derivative could be an excellent ligand for the complexation of copper(II). Additionally, the N-2-hydroxybenzyl groups were chosen due to their known ability to coordinate the gallium(III) cation. Due to the small size of the latter cation and its particular propensity to form hexacoordinate complexes, it was also expected that there would be a good ability of both ligands for the uptake of Ga³⁺. Surprisingly, the results revealed that the cyclen derivative H₂do2ph is the best ligand for the coordination of Cu ²⁺ and Ga³⁺ cations, not only from their thermodynamic stability as expected but also from their kinetic inertness, when compared with its cross-bridged counterpart.