The critical role of ligand topology: strikingly different properties of Gd(iii) complexes with regioisomeric AAZTA derivatives. Issue 10 (7th April 2022)

• Record Type: Journal Article
• Authors: Martinelli, Jonathan; Boccalon, Mariangela; Horvath, David; Esteban-Gomez, David; Platas-Iglesias, Carlos; Baranyai, Zsolt; Tei, Lorenzo
• Is Part Of: Inorganic chemistry frontiers. Volume 9:Issue 10(2022)
• Page Start: 2271
• Page End: 2283
• Publication Date: 2022-04-07
• Subjects: Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/d2qi00451h
• Languages: English
• ISSNs: 2052-1553

Abstract

Abstract : Two regioisomeric Gd(III) complexes with heptadentate AAZTA-like ligands show different hydration state ( q = 1 and 2) and astonishingly different thermodynamic stability and dissociation kinetics. Abstract : The substitution of an acetate pendant arm on the endocyclic or exocyclic nitrogen atoms of AAZTA with a hydroxybenzyl group results in two regioisomeric Gd(iii ) complexes with different hydration numbers, thermodynamic stabilities differing by 5.5 log K units and remarkably different kinetic inertness. The ligand functionalized with the phenol group on the exocyclic N atom (AAZ3A-exoHB) forms a Gd(iii ) complex with remarkably high stability (log K GdL = 25.06) thanks to the tight coordination of the phenol group, which presents a rather low protonation constant (log K GdHL = 3.22). Conversely, the complex formed with the ligand bearing a phenol unit attached to an endocyclic N atom (AAZ3A-endoHB) is considerably less stable (log K GdL = 19.57) and more prone to protonation (log K GdHL = 6.22). Transmetallation kinetics studies in the presence of Cu(ii ) evidence that the Gd(iii ) complexes dissociate via the proton- and metal-assisted dissociation pathways, with the AAZ3A-exoHB derivative being considerably more inert. A detailed 1 H nuclear magnetic relaxation dispersion (NMRD) study coupled with 17 O NMR measurements demonstrates that the complex with AAZ3A-exoHB contains a single water molecule in the inner coordination sphere, while the AAZ3A-endoHB analogue has two water molecules coordinated to the metal ion endowed with significantly different water exchange rates. Finally, a binding study of the two complexes with human serum albumin showed a stronger interaction and higher relaxivity ( r b1 = 36.5 mM −1 s −1 at 30 MHz and 298 K) for Gd(AAZ3A-endoHB) than for Gd(AAZ3A-exoHB). Overall, this study highlights the importance that ligand topology has in the properties of Gd(iii ) complexes relevant in the field of magnetic resonance imaging (MRI).