Thermodynamic and structural properties of Eu3+complexes of a new 12-membered tetraaza macrocycle containing pyridine and N-glutaryl groups as pendant arms: characterization of three complexing successive phases.

Abstract

A new polyazamacrocyclic ligand (called pctga) containing pyridine and N-glutaryl arms has been synthesized as a potential agent for MRI (magnetic resonance imaging). Three series of successive complexes formed with Eu(3+) were characterized by at least two of the following methods: potentiometry, EXAFS or luminescence spectrometry. In the immediate complexes [EuH(h)(pctga)(H2O)6](h-3)+**, the metal ion is bound to the oxygen atoms of the three internal carboxylate groups and to six water molecules. As the lanthanide moves into the macrocyclic cavity, these species rapidly evolve into the intermediate metastable complexes [EuH(h)(pctga)(H2O)4](h-3)+*. The formation of two new bonds with the nitrogen atoms of the tetraazamacrocycle decreased the number of coordinated water molecules to four. In the final thermodynamically stable complexes [EuH(h)(pctga)(H2O)(2)](h-3)+, the pctga is bound to the europium(III) in a heptadentate manner, via the four nitrogen atoms of the tetraazamacrocycle and the three oxygen atoms of the internal carboxylate groups. The coordination number of the metal ion is completed to nine with two inner-sphere water molecules. The mean hydration numbers were calculated from the values of the bimolecular quenching constant k(q) of the luminescence species. The thermodynamic parameters corresponding to the protonation constants of the ligand and to the formation constants of the various intermediate and final complexes were determined from potentiometric measurements. They show that the complex species have some specific thermodynamic and structural properties inherent to the N-glutaryl groups and to the pyridine cycle. The insertion of this aromatic substructure rigidifies the ligand and sensibly diminishes the value of the overall formation constant (log beta(110) = 18.66(5)). This whole study allows us to propose a complexation mechanism for the system Eu(3+)/pctga in solution which is a mixture of the ones determined for the ligands dota and tced.

Gadolinium(iii) complexes as MRI contrast agents: ligand design and properties of the complexes

“…However, larger differences in stability constants were found for Eu(III) complexes of the pyDO3A derivative with glutarate arms (log K EuL 18.7), analogous to TCED (Chart 5, log K EuL 24.0). 134 Similar trends to those of macrocycles were found for complexes of the DTTA derivatives (Chart 3), which are less stable (∼19) than the DTPA complex. 56, 57 The exchange of acetate arms for propionate arms in pyDO3A led to a large decrease in stability constants.…”

Expanding the Family of Pyclen-Based Ligands Bearing Pendant Picolinate Arms for Lanthanide Complexation

“…First, the absence of one acetate arm leads to heptacoordinated Ln 3+ complexes, allowing the access of two water molecules to the metal center. 21 As a result, Gd 3+ complexes of pcta and its derivatives show relaxivities that are considerably higher than that of Gd(dota) − . 22 It also forms charge-neutral Ln 3+ complexes, which allows preparing lipophilic derivatives for selective targeting of cancer, altering biodistribution properties, 23−25 or targeting amyloid aggregates.…”

Synthesis and Characterization of Ligands and their Gadolinium(III) Complexes

“…In the case of the symmetrical substitution, the "naked" macrocycle is prepared in the first step and the pendants are introduced in the second step. This strategy was used for preparation of tri(substituted) ligands with acetate (H 3 PCTA) [340,350], glutarate [351], propionate [352], and acetamide pendant arms [353] as well as for phosphonate derivative (H 6 PCTP) [354,355]. A different strategy can be used for ligands with mixed pendant arms.…”