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Gadolinium(III) Complexes of dota‐Derived N ‐Sulfonylacetamides (H 4 (dota‐NHSO 2 R)=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

2005; Wiley; Volume: 88; Issue: 3 Linguagem: Inglês

10.1002/hlca.200590041

1522-2675

Silvio Aime, Mauro Botta, Giancarlo Cravotto, Luca Frullano, Giovanni B. Giovenzana, Simonetta Geninatti Crich, Giovanni Palmisano, Massimo Sisti,

Electron Spin Resonance Studies

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 m M −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.