[摘要]：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 detg. the effectiveness of an agent is the difference between the relativity 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 mol. wt. agent by conjugating it to a macromol. 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 byproduct 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 av. of 96 chelates per dendrimer. The relativity 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 relativity pH response, Dr1 of our agent from just 51% for the original low mol. wt. chelate to 122% for the dendrimer.
