TY - JOUR
T1 - Designing novel contrast agents for magnetic resonance imaging. Synthesis and relaxometric characterization of three gadolinium(III) complexes based on functionalized pyridine-containing macrocyclic ligands
AU - Aime, Silvio
AU - Gianolio, Eliana
AU - Corpillo, Davide
AU - Cavallotti, Camilla
AU - Palmisano, Giovanni
AU - Sisti, Massimo
AU - Giovenzana, Giovanni B.
AU - Pagliarin, Roberto
PY - 2003
Y1 - 2003
N2 - The three novel pyridine-containing 12-membered macrocyclic ligands 1-3 were synthesized. The coordinating arms are represented by three acetate moieties in 1 and 3 and by one acetate and two phosphonate moieties in 2. In all three ligands, the acetate arm in the distal position is substituted, with a benzyl group in 1 and 2 and with an arylmethyl moiety in 3. The relaxivities r1p (20 MHz, 25°) of GdIII complexes are: GD · 1, r1p = 8.3 mm-1 s-1; GD · 2, r1p = 8.1 mM-1 s-1; Gd · 3, r1p = 10.5 mM-1 s-1. 1H-NMRD and 17O-NMR T2 data show that Gd · 1 and Gd · 3 contain two H2O molecules in the inner sphere, whereas the presence of two phosphonate arms allows the coordination of only one H2O molecule in Gd · 2. Interestingly, the exchange lifetime of coordinated H2O in the three complexes is similar in spite of the difference in the coordination number of the GdIII ion (i.e., 9 in Gd · 1 and Gd · 3, and 8 in Gd · 2). 1H-Relaxometric measurements at different pH and in the presence of lactate and oxalate were carried out to get some insight into the formation of ternary complexes from Gd · 1 and Gd · 3. Finally, it was found that binding to human-serum albumin (HSA) of Gd · 1 and Gd · 2, though weak, yields limited relaxivity enhancements, likely as a consequence of effects on the hydration sphere caused by donor atoms on the surface of the protein.
AB - The three novel pyridine-containing 12-membered macrocyclic ligands 1-3 were synthesized. The coordinating arms are represented by three acetate moieties in 1 and 3 and by one acetate and two phosphonate moieties in 2. In all three ligands, the acetate arm in the distal position is substituted, with a benzyl group in 1 and 2 and with an arylmethyl moiety in 3. The relaxivities r1p (20 MHz, 25°) of GdIII complexes are: GD · 1, r1p = 8.3 mm-1 s-1; GD · 2, r1p = 8.1 mM-1 s-1; Gd · 3, r1p = 10.5 mM-1 s-1. 1H-NMRD and 17O-NMR T2 data show that Gd · 1 and Gd · 3 contain two H2O molecules in the inner sphere, whereas the presence of two phosphonate arms allows the coordination of only one H2O molecule in Gd · 2. Interestingly, the exchange lifetime of coordinated H2O in the three complexes is similar in spite of the difference in the coordination number of the GdIII ion (i.e., 9 in Gd · 1 and Gd · 3, and 8 in Gd · 2). 1H-Relaxometric measurements at different pH and in the presence of lactate and oxalate were carried out to get some insight into the formation of ternary complexes from Gd · 1 and Gd · 3. Finally, it was found that binding to human-serum albumin (HSA) of Gd · 1 and Gd · 2, though weak, yields limited relaxivity enhancements, likely as a consequence of effects on the hydration sphere caused by donor atoms on the surface of the protein.
UR - http://www.scopus.com/inward/record.url?scp=0037254308&partnerID=8YFLogxK
U2 - 10.1002/hlca.200390061
DO - 10.1002/hlca.200390061
M3 - Article
SN - 0018-019X
VL - 86
SP - 615
EP - 632
JO - Helvetica Chimica Acta
JF - Helvetica Chimica Acta
IS - 3
ER -