title: Phosphinic derivative of DTPA conjugated to a G5 PAMAM dendrimer: an 17O and 1H relaxation study of its Gd(III) complex.
abstract: A DTPA-based chelate containing one phosphinate group was conjugated to a generation 5 polyamidoamine (PAMAM) dendrimer via a benzylthiourea linkage. The Gd(III) complex of this novel conjugate has potential as a contrast agent for magnetic resonance imaging (MRI). The chelates bind Gd3+via three nitrogen atoms, four carboxylates and one phosphinate oxygen, and one water molecule completes the inner coordination sphere. The monomer Gd(III) chelates bearing nitrobenzyl and aminobenzyl groups ([Gd(DTTAP-bz-NO2)(H2O)]2- and [Gd(DTTAP-bz-NH2)(H2O)]2-) as well as the dendrimeric Gd(III) complex G5-(Gd(DTTAP))63) were studied by multiple-field, variable temperature 17O and 1H NMR. The rate of water exchange is faster than that of [Gd(DTPA)(H2O)]2- and very similar on the two monomeric complexes (8.9 and 8.3 x 10(6) s-1 for [Gd(DTTAP-bz-NO2)(H2O)]2- and [Gd(DTTAP-bz-NH2)(H2O)]2-, respectively), while it is decreased on the dendrimeric conjugate (5.0 x 10(6) s-1). The Gd(III) complex of the dendrimer conjugate has a relaxivity of 26.8 mM-1 s-1 at 37 degrees C and 0.47 T (corresponding to 1H Larmor frequency of 20 MHz). Given the contribution of the second sphere water molecules to the overall relaxivity, this value is slightly higher than those reported for similar size dendrimers. The experimental 17O and 1H NMR data were fitted to the Solomon-Bloembergen-Morgan equations extended with a contribution from second coordination sphere water molecules. The rotational dynamics of the dendrimeric conjugate was described in terms of global and local motions with the Lipari-Szabo approach.
authors.affiliation: Department of Inorganic Chemistry, Charles University, Hlavova 2030, 12840 Prague, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Lebdusková
authors.forename: Angélique
authors.initials: A
authors.lastname: Sour
authors.forename: Lothar
authors.initials: L
authors.lastname: Helm
authors.forename: Eva
authors.initials: E
authors.lastname: Tóth
authors.forename: Jan
authors.initials: J
authors.lastname: Kotek
authors.forename: Ivan
authors.initials: I
authors.lastname: Lukes
authors.forename: André E
authors.initials: AE
authors.lastname: Merbach
mesh_terms: D002614:Chelating Agents / Q000138:chemical synthesis*; D050091:Dendrimers; D005682:Gadolinium / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry*; D007202:Indicators and Reagents; D049449:Luminescence; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010103:Oxygen Isotopes / Q000737:chemistry*; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D010720:Phosphines / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry*; D012997:Solvents
chemical_list: D002614:Chelating Agents; D050091:Dendrimers; D007202:Indicators and Reagents; D010103:Oxygen Isotopes; C104700:PAMAM Starburst; D010720:Phosphines; D011073:Polyamines; D012997:Solvents; D004369:Pentetic Acid; D006859:Hydrogen; D005682:Gadolinium