A benzene-core trinuclear GdIII complex: towards the optimization of relaxivity for MRI contrast agent applications at high magnetic field.
A novel ligand, H(12)L, based on a trimethylbenzene core bearing three methylenediethylenetriamine-N,N,N'',N''-tetraacetate moieties (-CH(2)DTTA(4-)) for Gd(3+) chelation has been synthesized, and its trinuclear Gd(3+) complex [Gd(3)L(H(2)O)(6)](3-) investigated with respect to MRI contrast agent applications. A multiple-field, variable-temperature (17)O NMR and proton relaxivity study on [Gd(3)L(H(2)O)(6)](3-) yielded the parameters characterizing water exchange and rotational dynamics. On the basis of the (17)O chemical shifts, bishydration of Gd(3+) could be evidenced. The water exchange rate, k(ex)(298)=9.0+/-3.0 s(-1) is around twice as high as k(ex)(298) of the commercial [Gd(DTPA)(H(2)O)](2-) and comparable to those on analogous Gd(3+)-DTTA chelates. Despite the relatively small size of the complex, the rotational dynamics had to be described with the Lipari-Szabo approach, by separating global and local motions. The difference between the local and global rotational correlation times, tau(lO)(298)=170+/-10 ps and tau(gO)(298)=540+/-100 ps respectively, shows that [Gd(3)L(H(2)O)(6)](3-) is not fully rigid; its flexibility originates from the CH(2) linker between the benzene core and the poly(amino carboxylate) moiety. As a consequence of the two inner-sphere water molecules per Gd(3+), their close to optimal exchange rate and the appropriate size and limited flexibility of the molecule, [Gd(3)L(H(2)O)(6)](3-) has remarkable proton relaxivities when compared with commercial contrast agents, particularly at high magnetic fields (r(1)=21.6, 17.0 and 10.7 mM(-1)s(-1) at 60, 200 and 400 MHz respectively, at 25 degrees C; r(1) is the paramagnetic enhancement of the longitudinal water proton relaxation rate, referred to 1 mM concentration of Gd(3+)).
Livramento
João Bruno
JB
Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne, ISIC, BCH, CH-1015, Lausanne, Switzerland.
Helm
Lothar
L
Sour
Angélique
A
O'Neil
Conlin
C
Merbach
André E
AE
Tóth
Eva
E
D001554:Benzene / Q000737:chemistry*; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry; D003287:Contrast Media / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D008024:Ligands; D008279:Magnetic Resonance Imaging / Q000379:methods; D008280:Magnetics; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D004369:Pentetic Acid / Q000031:analogs & derivatives / Q000737:chemistry
D002614:Chelating Agents; D003287:Contrast Media; D008024:Ligands; D009942:Organometallic Compounds; C060068:diethylenetriaminetetraacetic acid; D004369:Pentetic Acid; D005682:Gadolinium; D001554:Benzene