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A Pyrophosphate‐Responsive Gadolinium(III) MRI Contrast Agent
Author(s) -
Surman Andrew J.,
Bonnet Célia S.,
Lowe Mark P.,
Kenny Gavin D.,
Bell Jimmy D.,
Tóth Éva,
Vilar Ramon
Publication year - 2011
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201001397
Subject(s) - pyrophosphate , gadolinium , chemistry , lanthanide , amide , spectroscopy , luminescence , nuclear magnetic resonance spectroscopy , crystallography , ion , inorganic chemistry , nuclear magnetic resonance , stereochemistry , materials science , organic chemistry , enzyme , physics , optoelectronics , quantum mechanics
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.