TY - JOUR
T1 - Synthesis, relaxometric and photophysical properties of a new pH-responsive MRI contrast agent
T2 - The effect of other ligating groups on dissociation of a p-nitrophenolic pendant arm
AU - Woods, Mark
AU - Kiefer, Garry E.
AU - Bott, Simon
AU - Castillo-Muzquiz, Aminta
AU - Eshelbrenner, Carrie
AU - Michaudet, Lydie
AU - McMillan, Kenneth
AU - Mudigunda, Siva D.K.
AU - Ogrin, Doug
AU - Tircsó, Gyula
AU - Zhang, Shanrong
AU - Zhao, Piyu
AU - Sherry, A. Dean
PY - 2004/8/4
Y1 - 2004/8/4
N2 - Two gadolinium(III) chelates, GdNP-DO3A (1-methlyene-(p-NitroPhenol)-1,4,7, 10-tetraazacycloDOdecane-4,7,10-triAcetate) and GdNP-DO3AM (1-methlyene(p- NitroPhenol)-1,4,7,10-tetraazacycloDOdecane-4,7,10-triacetAMide), containing a single nitrophenolic pendant arm plus either three acetate or three amide pendant arms were synthesized and characterized. The properties of the gadolinium, terbium, and dysprosium complexes of these ligands were examined as a function of pH. The extent and mechanism of the changes in water relaxivity with pH of each gadolinium complex was found to differ substantially for the two complexes. The water relaxivity of Gd(NP-DO3A) increases from 4.1 mM -1 s-1 at pH 9 to 7.0 mM-1 s-1 at pH 5 as a result of acid-catalyzed dissociation of the nitrophenol from the lanthanide. The nitrophenol group in Gd(NP-DO3AM) does not dissociate from the metal center even at pH 5; therefore, the very modest increase in relaxivity in this complex must be ascribed to an increase in prototropic exchange rate of the bound water and/or phenolic protons.
AB - Two gadolinium(III) chelates, GdNP-DO3A (1-methlyene-(p-NitroPhenol)-1,4,7, 10-tetraazacycloDOdecane-4,7,10-triAcetate) and GdNP-DO3AM (1-methlyene(p- NitroPhenol)-1,4,7,10-tetraazacycloDOdecane-4,7,10-triacetAMide), containing a single nitrophenolic pendant arm plus either three acetate or three amide pendant arms were synthesized and characterized. The properties of the gadolinium, terbium, and dysprosium complexes of these ligands were examined as a function of pH. The extent and mechanism of the changes in water relaxivity with pH of each gadolinium complex was found to differ substantially for the two complexes. The water relaxivity of Gd(NP-DO3A) increases from 4.1 mM -1 s-1 at pH 9 to 7.0 mM-1 s-1 at pH 5 as a result of acid-catalyzed dissociation of the nitrophenol from the lanthanide. The nitrophenol group in Gd(NP-DO3AM) does not dissociate from the metal center even at pH 5; therefore, the very modest increase in relaxivity in this complex must be ascribed to an increase in prototropic exchange rate of the bound water and/or phenolic protons.
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U2 - 10.1021/ja048299z
DO - 10.1021/ja048299z
M3 - Article
C2 - 15281814
AN - SCOPUS:3342941448
SN - 0002-7863
VL - 126
SP - 9248
EP - 9256
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 30
ER -