The effect of ligand scaffold size on the stability of tripodal hydroxypyridonate gadolinium complexes.
The variation of the size of the capping scaffold which connects the hydroxypyridonate (HOPO) binding units in a series of tripodal chelators for gadolinium (Gd) complexes has been investigated. A new analogue of TREN-1-Me-3,2-HOPO (1) (TREN = tri(ethylamine)amine) was synthesized: TREN-Gly-1-Me-3,2-HOPO (2) features a glycine spacer between the TREN cap and HOPO binding unit. TRPN-1-Me-3,2-HOPO (3) has a propylene-bridged cap, as compared to the ethylene bridges within the TREN cap of the parent complex. Thermodynamic equilibrium constants for the acid-base properties of 2 and the Gd(3+) complexation strength of 2 and 3 were measured and are compared with that of the parent ligand. The most basic ligand is 2 while 3 is the most acidic. Both 2 and 3 form Gd(3+) complexes of similar stability (pGd = 16.7 and 15.6, respectively) and are less stable than the parent complex Gd-1 (pGd = 19.2). Two of the three complexes are more stable than the bis(methylamide)diethylenetriamine pentaacetate complex Gd(DTPA-BMA) (pGd = 15.7) while the other is of comparable stability. Enlargement of the ligand scaffold decreases the stability of the Gd(3+) complexes and indicates that the TREN scaffold is superior to the TRPN and TREN-Gly scaffolds. The proton relaxivity of Gd-2 is 6.6 mM(-)(1) s(-)(1) (20 MHz, 25 degrees C, pH 7.3), somewhat lower than the parent Gd-1 but higher than that of the MRI contrast agents in clinical practice. The pH-independent relaxivity of Gd-2 is uncharacteristic of this family of complexes and is discussed.
O'Sullivan
Brendon
B
Department of Chemistry, University of California, Berkeley, California 94720, USA.
Doble
Dan M J
DM
Thompson
Marlon K
MK
Siering
Carsten
C
Xu
Jide
J
Botta
Mauro
M
Aime
Silvio
S
Raymond
Kenneth N
KN
D003287:Contrast Media; D005682:Gadolinium / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D011728:Pyridones / Q000737:chemistry*; D013816:Thermodynamics
D003287:Contrast Media; D008024:Ligands; D009942:Organometallic Compounds; D011728:Pyridones; D005682:Gadolinium