Towards rational design of fast water-exchanging Gd(dota-like) contrast agents? Importance of the M/m ratio

Dunand, F.A.; Dickins, R.S.; Parker, D.; Merbach, A.E.

Abstract

H-1 NMR line-shape analysis and magnetisation-transfer experiments at variable temperature and pressure have been used to elucidate the solution dynamics of both M and m isomers of three [Eu(dota-tetraamide)(H2O)](3+) complexes. The direct H-1 NMR observation of the bound water signal allows the water- exchange rates on each isomer to be measured individually. They are definitely independent of the ligand for both M and m isomers (M: k(ex)(298) = 0.2 x 10(3)s(-1) for [Eu(dotam)(H2O)](3+), 8.2 +/- 02 x 10(3) s(-1) for [Eu(dtma)(H2O)](3+) and 11.2 +/- 1.4 x 10(3) s(-1) for [Eu(dotmam)(H2O)](3+), m: k(ex)(298) = 474 +/- 130 x 10(3) s(- 1) for [Eu(dotam)(H2O)](3+), 357 +/- 92 x 10(3) s(-1) for [Eu(dtma)(H2O)](3+)), and proceed through a dissociative mechanism (M isomers: DeltaV(double dagger) = + 4.9 cm(3) mol(- 1) for [Eu(dotam)(H2O)](3+) and + 6.9 cm(3) mol(-1) for [Eu(dtma)(H2O)](3+)). The overall water exchange only depends on the M/m isomeric ratio. The m isomer, which exchanges more quickly, is favoured by a-substitution of the ring nitrogen. Therefore the synthesis of DOTA-like ligands, which predominantly form complexes in the m form, should be a sufficient condition to ensure faster water exchange on potential Gd-III-based contrast agents. Furthermore the activation parameters for the water-exchange and isomerisation processes are both compatible with a nonhydrated complex as intermediate.

Citation

Dunand, F., Dickins, R., Parker, D., & Merbach, A. (2001). Towards rational design of fast water-exchanging Gd(dota-like) contrast agents? Importance of the M/m ratio. Chemistry - A European Journal, 7(23), 5160-5167

• Journal Article Type: Article
• Publication Date: 2001-12
• Journal: Chemistry - A European Journal
• Print ISSN: 0947-6539
• Electronic ISSN: 1521-3765
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 7
• Issue: 23
• Pages: 5160-5167
• Public URL: https://durham-repository.worktribe.com/output/1556299
• Publisher URL: <Go to ISI>://000172599900018