Monopicolinate Cyclen and Cyclam Derivatives for Stable Copper(II) Complexation

The syntheses of a new 1,4,7,10-tetraazacyclododecane
(cyclen)
derivative bearing a picolinate pendant arm (HL1), and
its 1,4,8,11-tetraazacyclotetradecane (cyclam) analogue HL2, were achieved by using two different selective-protection methods
involving the preparation of cyclen-bisaminal or phosphoryl cyclam
derivatives. The acid–base properties of both compounds were
investigated as well as their coordination chemistry, especially with
Cu2+, in aqueous solution and in solid state. The copper­(II)
complexes were synthesized, and the single crystal X-ray diffraction
structures of compounds of formula [Cu­(HL)]­(ClO4)2·H2O (L = L1 or L2), [CuL1]­(ClO4) and [CuL2]­Cl·2H2O, were determined. These studies revealed that protonation
of the complexes occurs on the carboxylate group of the picolinate
moiety. Stability constants of the complexes were determined at 25.0
°C and ionic strength 0.10 M in KNO3 using potentiometric
titrations. Both ligands form complexes with Cu2+ that
are thermodynamically very stable. Additionally, both HL1 and HL2 exhibit an important selectivity for Cu2+ over Zn2+. The kinetic inertness in acidic medium
of both complexes of Cu2+ was evaluated by spectrophotometry
revealing that [CuL2]+ is much more inert
than [CuL1]+. The determined half-life values
also demonstrate the very high kinetic inertness of [CuL2]+ when compared to a list of copper­(II) complexes of
other macrocyclic ligands. The coordination geometry of the copper
center in the complexes was established in aqueous solution from UV–visible
and electron paramagnetic resonance (EPR) spectroscopy, showing that
the solution structures of both complexes are in excellent agreement
with those of crystallographic data. Cyclic voltammetry experiments
point to a good stability of the complexes with respect to metal ion
dissociation upon reduction of the metal ion to Cu+ at
about neutral pH. Our results revealed that the cyclam-based ligand
HL2 is a very attractive receptor for copper­(II), presenting
a fast complexation process, a high kinetic inertness, and important
thermodynamic and electrochemical stability.