Modular synthesis of O-BODIPY dyes for cell microscopy

Abstract

We have developed a general post-synthetic strategy for the direct one-step incorporation of hydroxy acids and diacids at the boron atom of F-BODIPY dyes. The tethering reaction uses easy-to-handle reagents, has broad functional group compatibility and proceeds under mild conditions without requiring any prefunctionalization of the starting F-BODIPY to afford the corresponding O-BODIPY derivative in good yield. The orthogonal geometrical arrangement of the hydroxy acid or diacid moiety with respect to the mean plane of the BODIPY chromophore hampers intermolecular aggregation processes that quench fluorescence, while the covalent attachment to the boron atom has a minimal effect on the absorption properties of the chromophore. We have applied this strategy to the one-step tagging of BODIPYs for the custom modification of their solubility properties and to the preparation of fluorescent functional probes for mitochondria targeting.

In the first application, water-soluble and hydrolytically stable BODIPYs were prepared in a single step by incorporating a hydroxy acid solubility module having either neutral (tetra- and octaethylene glycol chains) or switterionic (sulfobetaine) hydrophilic tags. The resulting BODIPYs are valuable live cell imaging probes.

In the second application, we have designed the first fluorescent probes that are actively channelled into the mitochondrial matrix through the carnitine system in living cells. Our functional probes have a minimalist structural design based on the BODIPY chromophore and carnitine as a biotargeting element. The new probes selectively label mitochondria regardless of their membrane potential and in an enantioespecific way.