We thank the National Institutes of Health (RR-02584, CA-84697, CA96019, and EB-04285), the Robert A Welch Foundation (AT-584), and the Texas Advanced Technology Program for financial assistance.
Journal of the American Chemical Society
Contrast media (Diagnostic imaging) -- Synthesis, Ligands (Biochemistry), Magnetic resonance imaging, Hydrogen-ion concentration
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.
Woods, M., Kiefer, G. E., Bott, S., Castillo-Muzquiz, A., Eshelbrenner, C., Michaudet, L., ... & Zhang, S. (2004). Synthesis, relaxometric and photophysical properties of a new pH-responsive MRI contrast agent: The effect of other ligating groups on dissociation of ap-nitrophenolic pendant arm. Journal of the American Chemical Society, 126(30), 9248-9256.