title: Stable Mn(2+), Cu(2+) and Ln(3+) complexes with cyclen-based ligands functionalized with picolinate pendant arms.
abstract: 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 (Mn(2+), Cu(2+) and Gd(3+)) 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 (1)H-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 Mn(2+) 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 Mn(2+) 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 (k1 = 2.5(4) × 10(-3) and 8.3(4) × 10(-4) M(-1) s(-1) for [Gd(dodpa)](+) and [Gd(Medodpa)](+), respectively) are smaller than the value reported for [Gd(do3a)] (k1 = 2.5 × 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.
authors: Departamento de Química Fundamental, Universidade da Coruña, Rúa da Fraga 10, 15008, A Coruña, Spain. carlos.platas.iglesias@udc.es.
authors: Aurora
authors: A
authors: Rodríguez-Rodríguez
authors: Zoltán
authors: Z
authors: Garda
authors: Erika
authors: E
authors: Ruscsák
authors: David
authors: D
authors: Esteban-Gómez
authors: Andrés
authors: A
authors: de Blas
authors: Teresa
authors: T
authors: Rodríguez-Blas
authors: Luís M P
authors: LM
authors: Lima
authors: Maryline
authors: M
authors: Beyler
authors: Raphaël
authors: R
authors: Tripier
authors: Gyula
authors: G
authors: Tircsó
authors: Carlos
authors: C
authors: Platas-Iglesias
mesh_terms: D002384:Catalysis; D003300:Copper / Q000737:chemistry; D000080027:Cyclams; D004355:Drug Stability; D006571:Heterocyclic Compounds / Q000737:chemistry*; D007700:Kinetics; D028581:Lanthanoid Series Elements / Q000737:chemistry; D008024:Ligands; D008345:Manganese / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry*; D010848:Picolinic Acids / Q000737:chemistry*; D011789:Quantum Theory; D014867:Water / Q000737:chemistry
chemical_list: D000080027:Cyclams; D006571:Heterocyclic Compounds; D028581:Lanthanoid Series Elements; D008024:Ligands; D009942:Organometallic Compounds; D010848:Picolinic Acids; D014867:Water; D008345:Manganese; D003300:Copper; C038072:cyclen; C030614:picolinic acid