Why was TLD1433 preferred over TLD1633?The answer is in
Dr. McFarland's (and
Dr. Lilge's) paper describing the development of
TLD1433. The entire text is available online at:
Transition Metal Complexes and Photodynamic Therapy from a Tumor-Centered Approach: Challenges, Opportunities, and Highlights from the Development of TLD1433 "...Our current hypothesis is that TLD1433 and TLD1633 act as supercatalysts, producing more than one ROS or other reactive species per photon absorbed per molecule when electron-transfer reactions are involved ...
Considering the potency of TLD1633, it may seem odd that TLD1433 was selected instead. TLD1433 was prioritized over the other compound for a number of reasons, including:
(1) there were more synthetic steps required for producing TLD1633, and those steps were low yielding (unoptimized at that time) and required expensive catalysts,
(2) there was more batch-to-batch variability with TLD1633,
(3) the theranostic capacity of TLD1433 was greater (i.e., its luminescence quantum yield was higher), and
(4) we were relatively far along in our pre-clinical studies with TLD1433 by the time the synthesis of TLD1633 was optimized to produce the larger batches required for in vivo studies...."