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Chemistry - A European Journal

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Dendrimers -- Synthesis, Contrast media (Diagnostic imaging), Rare earth metals -- Magnetic properties


The design of effective pH responsive MRI contrast agents is a key goal in the development of new diagnostic methods for conditions such as kidney disease and cancer. A key factor determining the effectiveness of an agent is the difference between the relaxivity of the “on” state compared to that of the “off” state. In this paper, we demonstrate that it is possible to improve the pH-responsive action of a low molecular weight agent by conjugating it to a macromolecular construct. The synthesis of a bifunctional pH responsive agent is reported. As part of that synthetic pathway we examine the Ing–Manske reaction, identifying an undesirable by-product and establishing effective conditions for promoting a clean and effective reaction. Reaction of the bifunctional pH responsive agent with a G5-PAMAM dendrimer yielded a product with an average of 96 chelates per dendrimer. The relaxivity of the dendrimer conjugate rises from 10.8 mM−1 s−1 (pH 9) to 24.0 mM−1 s−1 (pH 6) per Gd3+ ion. This more than doubles the relaxivity pH response, Δr1, of our agent from just 51% for the original low molecular weight chelate to 122% for the dendrimer.


This is the pre-peer reviewed version of the following article: Ali, M. M., Woods, M., Caravan, P., Opina, A. C., Spiller, M., Fettinger, J. C., & Sherry, A. D. (2008). Synthesis and relaxometric studies of a dendrimer‐based pH‐responsive MRI contrast agent. Chemistry–A European Journal, 14(24), 7250-7258, which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

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



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