title: A pyrophosphate-responsive gadolinium(III) MRI contrast agent.
abstract: This study shows that the relaxivity and optical properties of functionalised lanthanide-DTPA-bis-amide complexes (lanthanide=Gd(3+) and Eu(3+) , DTPA=diethylene triamine pentaacetic acid) can be successfully modulated by addition of specific anions, without direct Ln(3+) /anion coordination. Zinc(II)-dipicolylamine moieties, which are known to bind strongly to phosphates, were introduced in the amide "arms" of these ligands, and the interaction of the resulting Gd-Zn(2) complexes with a range of anions was screened by using indicator displacement assays (IDAs). Considerable selectivity for polyphosphorylated species (such as pyrophosphate and adenosine-5'-triphosphate (ATP)) over a range of other anions (including monophosphorylated anions) was apparent. In addition, we show that pyrophosphate modulates the relaxivity of the gadolinium(III) complex, this modulation being sufficiently large to be observed in imaging experiments. To establish the binding mode of the pyrophosphate and gain insight into the origin of the relaxometric modulation, a series of studies including UV/Vis and emission spectroscopy, luminescence lifetime measurements in H(2) O and D(2) O, (17) O and (31) P NMR spectroscopy and nuclear magnetic resonance dispersion (NMRD) studies were carried out.
authors.affiliation: Department of Chemistry, Imperial College London, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Surman
authors.forename: Célia S
authors.initials: CS
authors.lastname: Bonnet
authors.forename: Mark P
authors.initials: MP
authors.lastname: Lowe
authors.forename: Gavin D
authors.initials: GD
authors.lastname: Kenny
authors.forename: Jimmy D
authors.initials: JD
authors.lastname: Bell
authors.forename: Eva
authors.initials: E
authors.lastname: Tóth
authors.forename: Ramon
authors.initials: R
authors.lastname: Vilar
mesh_terms: D000838:Anions; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry; D011756:Diphosphates / Q000138:chemical synthesis* / Q000737:chemistry*; D005063:Europium / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry*; D008163:Luminescent Measurements; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D004369:Pentetic Acid / Q000737:chemistry; D015032:Zinc / Q000737:chemistry
chemical_list: D000838:Anions; D003287:Contrast Media; D011756:Diphosphates; D009942:Organometallic Compounds; D005063:Europium; D004369:Pentetic Acid; D005682:Gadolinium; D015032:Zinc