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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
Author(s) -
Aime Silvio,
Botta Mauro,
Cravotto Giancarlo,
Frullano Luca,
Giovenzana Giovanni B.,
Geninatti Crich Simonetta,
Palmisano Giovanni,
Sisti Massimo
Publication year - 2005
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200590041
Subject(s) - chemistry , dota , lanthanide , gadolinium , molecule , delocalized electron , coordination sphere , crystallography , stereochemistry , relaxation (psychology) , ion , chelation , crystal structure , inorganic chemistry , organic chemistry , social psychology , psychology
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.