Optimizing the Synthesis of a Theranostic Rhodamine

Current designs for small molecule theranostics, which serve both a diagnostic and therapeutic role, often involve dyes linked to therapeutic agents through a cleavable, traceless linker. In order to facilitate the separation of the dye from the therapeutic in response to a biological or chemical stimulus, linkers must incorporate elements of molecular logic, increasing their complexity and the overall bulk of the small molecule theranostic. By combining the self-immolative molecular logic of the linker into the structure of the dye itself, we hope to create a series of smaller, more atom-economical theranostics. Rhodamine dyes, which naturally possess aromatic rings with highly-tunable electron density, are promising candidates in this regard. Toward this end, we have synthesized a substituted rhodamine-precursor in 4 steps and 25% overall yield, utilizing a highly-optimized radical bromination. Upon completion of the rhodamine scaffold, we hope to explore the kinetics of its “turn-on” fluorescence and self-immolative drug release.