Synthesis, Relaxometric and Photophysical Properties of a New pH-Responsive MRI Contrast Agent: The Effect of Other Ligating Groups on Dissociation of a p-Nitrophenolic Pendant Arm

Authors

Mark Woods, Portland State UniversityFollow
Garry Kiefer, Dow Chemical CompanyFollow
Simon G. Bott, University of Houston
Aminta Castillo-Muzquiz, University of Texas at DallasFollow
Carrie Eshelbrenner, University of Texas at Dallas
Lydie Michaudet, University of Texas at Dallas
Kenneth McMillan, Dow Chemical CompanyFollow
Siva D.K. Mudigunda, Macrocyclics
Doug Ogrin, Rice University
Gyula Tircso, University of Texas at DallasFollow
Shanrong Zhang, University of Texas at DallasFollow
Piyu Zhao, University of Texas at DallasFollow
A. Dean Sherry, University of Texas at DallasFollow

Sponsor

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.

Published In

Journal of the American Chemical Society

Document Type

Post-Print

Publication Date

8-4-2004

Subjects

Contrast media (Diagnostic imaging) -- Synthesis, Ligands (Biochemistry), Magnetic resonance imaging, Hydrogen-ion concentration

Abstract

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.

Description

This is the authors' version of a paper that subsequently appeared in the Journal of the American Chemical Society, vol. 126, no. 30: 9248-9256. The version of record may be found at https://doi.org/10.1021/ja048299z

Copyright ©2004 American Chemical Society

Note: At the time of writing Mark Woods was affiliated with the University of Texas at Dallas.

DOI

10.1021/ja048299z

Persistent Identifier

https://archives.pdx.edu/ds/psu/32576

Citation Details

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.