Gadolinium complexes of highly rigid, open-chain ligands containing a cyclobutane ring in the backbone : Decreasing ligand denticity might enhance kinetic inertness
Porcar Tost, Oriol (Universitat Autònoma de Barcelona. Departament de Química)
Olivares Montia, José Antonio (Universitat Autònoma de Barcelona. Departament de Química)
Pallier, Agnès (Centre National de la Recherche Scientifique. Université d'Orléans. Centre de Biophysique Moléculaire)
Esteban-Gómez, David (Universidade da Coruña. Departamento de Química)
Illa, Ona (Universitat Autònoma de Barcelona. Departament de Química)
Platas-Iglesias, Carlos (Universidade da Coruña. Departamento de Química)
Tóth, Éva (Centre National de la Recherche Scientifique. Université d'Orléans. Centre de Biophysique Moléculaire)
Ortuño Mingarro, Rosa María (Universitat Autònoma de Barcelona. Departament de Química)

Data:	2019
Resum:	In an effort to explore novel ligand scaffolds for stable and inert lanthanide complexation in magnetic resonance imaging contrast agent research, three chiral ligands containing a highly rigid (1S,2S)-1,2-cyclobutanediamine spacer and different number of acetate and picolinate groups were efficiently synthesized. Potentiometric studies show comparable thermodynamic stability for the Gd3+ complexes formed with either the octadentate (L3)4- bearing two acetate or two picolinate groups or the heptadentate (L2)4- analogue bearing one picolinate and three acetate groups (log KGdL = 17. 41 and 18. 00 for [Gd(L2)]- and [Gd(L3)]-, respectively). In contrast, their dissociation kinetics is revealed to be very different: the monohydrated [Gd(L3)]- is considerably more labile, as a result of the significant kinetic activity of the protonated picolinate function, as compared to the bishydrated [Gd(L2)]-. This constitutes an uncommon example in which lowering ligand denticity results in a remarkable increase in kinetic inertness. Another interesting observation is that the rigid ligand backbone induces an unusually strong contribution of the spontaneous dissociation to the overall decomplexation process. Thanks to the presence of two inner-sphere water molecules, [Gd(L2)]- is endowed with high relaxivity (r1 = 7. 9 mM-1 s-1 at 20 MHz, 25 °C), which is retained in the presence of large excess of endogenous anions, excluding ternary complex formation. The water exchange rate is similar for [Gd(L3)]- and [Gd(L2)]-, while it is 1 order of magnitude higher for the trishydrated tetraacetate analogue [Gd(L1)]- (kex298 = 8. 1, 10, and 127 × 106 s-1, respectively). A structural analysis via density functional theory calculations suggests that the large bite angle imposed by the rigid (1S,2S)-1,2-cyclobutanediamine spacer could allow the design of ligands based on this scaffold with suitable properties for the coordination of larger metal ions with biomedical applications.
Ajuts:	Ministerio de Economía y Competitividad CTQ2016-77978-R
Drets:	Tots els drets reservats.
Llengua:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Publicat a:	Inorganic chemistry, Vol. 58, Issue 19 (October 2019) , p. 13170-13183, ISSN 1520-510X

DOI: 10.1021/acs.inorgchem.9b02044
PMID: 31524387

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