New synthesis of a high molecular weight ligand derived from dota; thermodynamic stability of the MRI contrast agent formed with gadolinium.
The new total synthesis in four steps of the compound P1041 is reported. This compound is a high molecular mass ligand (MW 6.32 kDa) derived from dota in which the four substituents are hydroxylated and contain amidic groups. The attribution of the nine protonation constants of P1041 is based on the comparison with the behaviour of the precursor ligands dota and tced, a tetracarboxylated derivative of dota. From these results, the studies of the systems P1041/Na(+) and P1041/Gd(3+) lead to the determination of the stability constants corresponding to the three species Na(P1041)H(h) (h = 0, 2 or 4) and to the five complexes Gd(P1041)H(h) (h = 0, 2, 3, 4 or 5). The complexing ability of P1041 towards Gd(3+) is compared with those of dota and tced. At physiological pH = 7.4, the very stable species Gd(P1041)H(4) (-) (currently named P792 in the literature) of this rapid clearance blood pool agent is predominant.
Pierrard
Jean-Claude
JC
Institut de Chimie Moléculaire de Reims, Groupe Chimie de Coordination, UMR CNRS 6229, Université de Reims Champagne-Ardenne, Reims Cedex 2, France. jc.pierrard@univ-reims.fr
Rimbault
Jean
J
Aplincourt
Michel
M
Le Greneur
Soizic
S
Port
Marc
M
D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry; D004355:Drug Stability; D005682:Gadolinium; D006573:Heterocyclic Compounds, 1-Ring; D008024:Ligands; D008279:Magnetic Resonance Imaging / Q000379:methods; D008970:Molecular Weight; D013816:Thermodynamics
D003287:Contrast Media; D006573:Heterocyclic Compounds, 1-Ring; D008024:Ligands; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D005682:Gadolinium