New synthesis of a high molecular weight ligand derived from dota; thermodynamic stability of the MRI contrast agent formed with gadolinium
✍ Scribed by Jean-Claude Pierrard; Jean Rimbault; Michel Aplincourt; Soizic Le Greneur; Marc Port
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 403 KB
- Volume
- 3
- Category
- Article
- ISSN
- 1555-4309
- DOI
- 10.1002/cmmi.258
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✦ Synopsis
Abstract
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 (currently named P792 in the literature) of this rapid clearance blood pool agent is predominant. Copyright © 2008 John Wiley & Sons, Ltd.