Monopicolinate Cross-Bridged Cyclam Combining Very Fast Complexation with Very High Stability and Inertness of Its Copper(II) Complex

The synthesis of a new cross-bridged
1,4,8,11-tetraazacyclotetradecane (cb-cyclam) derivative bearing a
picolinate arm (Hcb-te1pa) was achieved
by taking advantage of the proton sponge properties of the starting
constrained macrocycle. The structure of the reinforced ligand as
well as its acid–base properties and coordination properties
with Cu2+ and Zn2+ was investigated. The X-ray
structure of the free ligand showed a completely preorganized conformation
that lead to very fast copper­(II) complexation under mild conditions
(instantaneous at pH 7.4) or even in acidic pH (3 min at pH 5) at
room temperature and that demonstrated high thermodynamic stability,
which was measured by potentiometry (at 25 °C and 0.10 M in KNO3). The results also revealed that the complex exists as a
monopositive copper­(II) species in the intermediate pH range. A comparative
study highlighted the important selectivity for Cu2+ over
Zn2+. The copper­(II) complex was synthesized and investigated
in solution using different spectroscopic techniques and DFT calculations.
The kinetic inertness of the copper­(II) complex in acidic medium was
evaluated by spectrophotometry, revealing the very slow dissociation
of the complex. The half-life of 96 days, in 5 M HClO4,
and 465 min, in 5 M HCl at 25 °C, show the high kinetic stability
of the copper­(II) chelate compared to that of the corresponding complexes
of other macrocyclic ligands. Additionally, cyclic voltammetry experiments
underlined the perfect electrochemical inertness of the complex as
well as the quasi-reversible Cu2+/Cu+ redox
system. The coordination geometry of the copper center in the complex
was established in aqueous solution from UV–vis and EPR spectroscopies.