Alkynyl N-BODIPYs as reactive intermediates for the development of dyes for biophotonics

BODIPYs are outstanding modern dyes for many photonic applications due to their excellent photophysical properties, which can be adjusted by appropriate chemical modifications of the chromophore structure. To apply them in biophotonics, it is necessary to introduce additional functional groups for bio-recognition or for increasing water solubility, likely the main drawback in BODIPYs. Unfortunately, this is not an easy step in monochromophoric BODIPYs, because the introduction of additional functional groups can severely affect the optimized photophysical properties of the chromophore. In this sense, functionalization at boron should be a useful tool to endow BODIPY dyes with key properties, without affecting the ground photophysical properties of the involved chromophore. In this context, we have recently reported the straightforward preparation of N-BODIPYs, this is, BODIPYs having N-groups at boron, making it possible to introduce up to four different groups at boron through the pending nitrogen atoms. Thus, N-BODIPYs could be an attractive scaffold to engineer smart BODIPYs with multiple functions, which is especially interesting when developing BODIPYs for biophotonics. In this communication, we report a new approach for the rapid multifunctionalization of BODIPY dyes towards biophotonics, based on N-BODIPYs, through reactive intermediates based on alkynyl groups, which can be easily derivatized using click chemistry. This approach has been exemplified by the development of new dyes for cell bio-imaging, which have proven to successfully internalize into pancreatic cancer cells and accumulate in the mitochondria. The in vitro suitability for photodynamic therapy (PDT) was also analyzed and confirmed our compounds to be promising candidates for pancreatic cancer PDT.