TY - JOUR
T1 - The critical role of ligand topology
T2 - strikingly different properties of Gd(iii) complexes with regioisomeric AAZTA derivatives
AU - Martinelli, Jonathan
AU - Boccalon, Mariangela
AU - Horvath, David
AU - Esteban-Gomez, David
AU - Platas-Iglesias, Carlos
AU - Baranyai, Zsolt
AU - Tei, Lorenzo
N1 - Publisher Copyright:
© 2022 The Royal Society of Chemistry.
PY - 2022/3/30
Y1 - 2022/3/30
N2 - 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 KGdL = 25.06) thanks to the tight coordination of the phenol group, which presents a rather low protonation constant (log KGdHL = 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 KGdL = 19.57) and more prone to protonation (log KGdHL = 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 1H nuclear magnetic relaxation dispersion (NMRD) study coupled with 17O 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 (rb1 = 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).
AB - 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 KGdL = 25.06) thanks to the tight coordination of the phenol group, which presents a rather low protonation constant (log KGdHL = 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 KGdL = 19.57) and more prone to protonation (log KGdHL = 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 1H nuclear magnetic relaxation dispersion (NMRD) study coupled with 17O 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 (rb1 = 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).
UR - http://www.scopus.com/inward/record.url?scp=85129210944&partnerID=8YFLogxK
U2 - 10.1039/d2qi00451h
DO - 10.1039/d2qi00451h
M3 - Article
SN - 2052-1545
VL - 9
SP - 2271
EP - 2283
JO - Inorganic Chemistry Frontiers
JF - Inorganic Chemistry Frontiers
IS - 10
ER -