A gadolinium(III) complex of a carboxylic-phosphorus acid derivative of diethylenetriamine covalently bound to inulin, a potential macromolecular MRI contrast agent.
A novel conjugate of a polysaccharide and a Gd(III) chelate with potential as contrast agent for magnetic resonance imaging (MRI) was synthesized. The structure of the chelate was derived from H5DTPA by replacing the central pendant arm by a phosphinic acid functional group, which was covalently bound to the polysaccharide inulin. On the average, each monosaccharide unit of the inulin was attached to approximately one (0.9) chelate moiety. The average molecular weight is 23110 and the average number of Gd3+ ions per molecule is 24. The ligand binds the Gd3+ ion in an octadentate fashion via three nitrogen atoms, four carboxylate oxygen atoms, and one P-O oxygen atom, and its first coordination sphere is completed by a water molecule. This compound shows promising properties for application as a contrast agent for MRI thanks to a favorable residence lifetime of this water molecule (170 ns at 298 K), a relatively long rotational correlation time (866 ps at 298 K), and the presence of two water molecules in the second coordination sphere of the Gd3+ ion. Furthermore, its stability toward transmetalation with Zn(II) is as high as that of the clinically used [Gd(DTPA)(H2O)]2-.
Lebdusková
Petra
P
Laboratory of Applied Organic Chemistry and Catalysis, Delft University of Technology, Julianalaan 136, 2628 BL, The Netherlands.
Kotek
Jan
J
Hermann
Petr
P
Vander Elst
Luce
L
Muller
Robert N
RN
Lukes
Ivan
I
Peters
Joop A
JA
D003287:Contrast Media / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D007444:Inulin / Q000737:chemistry*; D008024:Ligands; D008279:Magnetic Resonance Imaging / Q000295:instrumentation*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry*; D011522:Protons; D013057:Spectrum Analysis; D014867:Water
D003287:Contrast Media; D008024:Ligands; D009942:Organometallic Compounds; D011073:Polyamines; D011522:Protons; C495578:diethylenetriamine-N'-methylene(p-aminobenzyl)phosphinic-N,N,N'',N''-tetraacetic acid gadlinium complex; C005391:diethylenetriamine; D014867:Water; D004369:Pentetic Acid; D007444:Inulin; D005682:Gadolinium