Toward optimized high-relaxivity MRI agents: the effect of ligand basicity on the thermodynamic stability of hexadentate hydroxypyridonate/catecholate gadolinium(III) complexes.
The thermodynamic stabilities of the Gd(III) complexes of five hexadentate ligands, which incorporate the 2,3-dihydroxyterephthalamide and 2,3-hydroxypyridonate chelating moieties, have been determined by potentiometric and spectrophotometric titration. The ligands were chosen to span a range of basicities while maintaining a similar tripodal structural motif, facilitating a study of the effect of ligand basicity on the thermodynamic stability of the Gd(III) complexes. The relative stability of the five complexes is found to be highly pH dependent, with the most acidic ligands forming the most stable complexes at low pH and more basic ligands forming more stable complexes at high pH. The most stable Gd(III) complex at a physiological pH of 7.4 is formed with a ligand of intermediate basicity and is of stability comparable to that of Gd(III) complexes that feature eight-coordinate amino-carboxylate ligands and are currently used as magnetic resonance imaging contrast agents in diagnostic medicine. A single-crystal X-ray structure of the intermediate compound 3-hydroxy-6-methyl-2-oxo-1,2-dihydropyridine-4-carboxylic acid ethyl ester is described: This compound crystallizes in the triclinic space group P1 with a = 7.4801(3) A, b = 8.0671(3) A, c = 8.3457(4) A, alpha = 72.242(2) degrees, beta = 80.693(2) degrees, gamma = 69.943(3) degrees, V = 449.60(3) A(3), Z = 2, and R = 0.042.
Doble
Dan M J
DM
Department of Chemistry, University of California, Berkeley, California 94720, USA.
Melchior
Marco
M
O'Sullivan
Brendon
B
Siering
Carsten
C
Xu
Jide
J
Pierre
Valérie C
VC
Raymond
Kenneth N
KN
D002396:Catechols / Q000138:chemical synthesis; D003287:Contrast Media / Q000138:chemical synthesis*; D018360:Crystallography, X-Ray; D005682:Gadolinium / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D008024:Ligands; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000138:chemical synthesis*; D011728:Pyridones / Q000138:chemical synthesis; D012996:Solutions; D013816:Thermodynamics
D002396:Catechols; D003287:Contrast Media; D007202:Indicators and Reagents; D008024:Ligands; D009942:Organometallic Compounds; D011728:Pyridones; D012996:Solutions; D005682:Gadolinium