Structural Variations in Carboxylated Bispidine Ligands: Influence of Positional Isomerism and Rigidity on the Conformation, Stability, Inertness and Relaxivity of their Mn2+ Complexes.
Fiche publication
Date publication
juillet 2023
Journal
Chemistry (Weinheim an der Bergstrasse, Germany)
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHARBONNIERE Loïc
Tous les auteurs :
Ndiaye D, Sy M, Thor W, Charbonnière LJ, Nonat AM, Tóth E
Lien Pubmed
Résumé
Mn2+ complexes of 2,4-pyridyl-disubstituted bispidine ligands have emerged as more biocompatible alternatives to Gd3+-based MRI probes. They display relaxivities comparable to that of commercial contrast agents and high kinetic inertness, unprecedented for Mn2+ complexes. The chemical structure, in particular the substituents on the two macrocyclic nitrogens N3 and N7, are decisive for the conformation of the Mn2+ complexes, and this will in turn determine their thermodynamic, kinetic and relaxation properties. We describe the synthesis of four ligands with acetate substituents in positions N3, N7 or both. We evidence that the bispidine conformation is dependent on N3 substitution, with direct impact on the thermodynamic stability, kinetic inertness, hydration state and relaxivity of the Mn2+ complexes. These results unambiguously show that (i) solely a chair-chair conformation allows for favorable inertness and relaxivity, and (ii) in this family such chair-chair conformation is accessible only for ligands without N3-appended carboxylates.
Mots clés
manganese * bispidine * MRI contrast agents * complex stability * relaxometry
Référence
Chemistry. 2023 07 20;:e202301880