Stable Mn2+, Cu2+ and Ln(3+) complexes with cyclen-based ligands functionalized with picolinate pendant arms

作者：Rodriguez Rodriguez Aurora; Garda Zoltan; Ruscsak Erika; Esteban Gomez David; de Blas Andres; Rodriguez Blas Teresa; Lima Luis M P; Beyler Maryline; Tripier Raphael^*; Tircso Gyula; Platas Iglesias Carlos

来源：Dalton Transactions, 2015, 44(11): 5017-5031.

DOI：10.1039/c4dt02985b

In this study we present the results of the equilibrium, dissociation kinetics, DFT and X-ray crystallographic studies performed on the complexes of metal ions of biomedical importance (Mn2+, Cu2+ and Gd3+) formed with octadentate ligands based on a cyclen platform incorporating two picolinate pendant arms (dodpa(2-) and Medodpa(2-)). The stability constants of the complexes were accessed by multiple methods (pH-potentiometry, direct and competition UV-vis spectrophotometry and H-1-relaxometry). The stability constants of the complexes formed with dodpa(2-) and Medodpa(2-) do not differ significantly (e.g. log K-[Mn(dodpa)] = 17.40 vs. log K-[Mn(Medodpa)] = 17.46, log K-[Cu(dodpa)] = 24.34-25.17 vs. log K-[Cu(Medodpa)] = 24.74 and log K-[Gd(dodpa)](+) = 17.27 vs. log K-[Gd(Medodpa)](+) = 17.59), which indicates that the steric hindrance brought by the methyl groups has no significant effect on the stability of the complexes. The stability constants of the Mn2+ complexes formed with the cyclen dipicolinates were found to be ca. 3 log K units higher than those determined for the complex of the cyclen monopicolinate (dompa(-)), which indicates that the second picolinate moiety attached to the backbone of the macrocycle is very likely coordinated to the Mn2+ ion. However, the stability of the [Cu(dodpa)] and [Cu(Medodpa)] complexes agrees well with the stability constant of [Cu(dompa)]+, in line with the hexadentate coordination around the metal ion observed in the X-ray structure of [Cu(Medodpa)]. The [Gd(dodpa)](+) and [Gd(Medodpa)](+) complexes display a fairly high kinetic inertness, as the rate constants of acid catalysed dissociation (k(1) = 2.5(4) x 10(-3) and 8.3(4) x 10(-4) M-1 s(-1) for [Gd(dodpa)](+) and [Gd(Medodpa)](+), respectively) are smaller than the value reported for [Gd(do3a)] (k(1) = 2.5 x 10(-2) M-1 s(-1)). The [Mn(dodpa)] complex was found to be more inert than [Mn(Medodpa)]. The results of the diffusion-ordered NMR spectroscopy (DOSY) and DFT calculations of diamagnetic [La(dodpa)](+) and [Lu(dodpa)](+) complexes indicate the formation of a trinuclear entity of the La complex in aqueous solution.

• 出版日期2015