Gadolinium(III) Complexes of dota-Derived N-Sulfonylacetamides (H4(dota-NHSO2R)=10-{2-[(R)sulfonylamino]-2-oxoethyl}-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic Acid): A New Class of Relaxation Agents for Magnetic Resonance Imaging Applications
✍ Scribed by Silvio Aime; Mauro Botta; Giancarlo Cravotto; Luca Frullano; Giovanni B. Giovenzana; Simonetta Geninatti Crich; Giovanni Palmisano; Massimo Sisti
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- German
- Weight
- 183 KB
- Volume
- 88
- Category
- Article
- ISSN
- 0018-019X
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✦ Synopsis
Abstract
Four new ligands for lanthanide ions based on the H~3~do3a (=1,4,7,10‐tetraazacyclododecane‐1,4,7‐triacetic acid) structure and bearing one N‐sulfonylacetamide arm were synthesized, i.e., H~4~dota‐NHSO~2~R=10‐{2‐[(R)sulfonylamino]‐2‐oxoethyl}‐1,4,7,10‐tetraazacyclododecane‐1,4,7‐triacetic acids 1a–e. A ^15^N‐NMR study of the ^15^N‐labelled Eu^3+^ complex of one such ligands, 1d, showed that the coordination of the N‐sulfonylacetamide arm involves the carbonyl O‐atom rather than the N‐atom. The relaxometric properties of the corresponding Gd^3+^ complexes were investigated as a function of pH and temperature. These complexes have relaxivities in the range 4.5–5.3 mM^−1^ s^−1^, at 20 MHz and 25°, and are characterized by a single H~2~O molecule in their inner coordination sphere. The mean residence lifetime of this molecule is relatively long (500–700 ns) compared to other anionic complexes. The slow rate of H~2~O exchange can be justified by the extensive delocalization of the negative charge on the N‐sulfonylacetamide arm. The long residence time of the coordinated H~2~O allowed the observation of the effect of the prototropic exchange on the relaxivity. The study of the interaction between the complex [Gd(1e)]‐ and HSA revealed a weak affinity constant highlighting the importance of a localized negative charge on the complex to promote a strong interaction with the protein.