Highly fluorinated molecules, known as perfluorocarbons, phase separate from aqueous and organic solutions due to their disinclination to participate in van der Waals interactions. The extreme hydrophobicity of perfluorocarbons allows perfluorocarbon (PFC) nanoemulsions to be formed via an energy-induced self-assembly process in the presence of small molecule or polymer surfactants. These stabilized droplets of fluorous solvent have been utilized for in vivo oxygen delivery, 19F NMR imaging, and ultrasound imaging and therapy. However, to localize cargo within the fluorous core of the emulsions and prevent leaching, significant fluorous content is required. Significant fluorous content can be defined as ≥ 60 weight percent fluorine in C(sp3 )−F bonds. While long, linear perfluorocarbon chains can provide fluorous solubility of tagged molecules, they have been shown to bioaccumulate. Short, branched fluorous tags can confer fluorous solubility, decrease aggregation, and be cleared from the body. We have developed a concise, mild synthesis of a branched alcohol with two C6F13 chains in three steps from commercially available materials. From this readily accessible alcohol, a series of branched fluorous tags with differing functional handles have been synthesized. These branched tags can be attached to various payloads for increased solubility in fluorous solvent as compared to their linear counterparts, providing a strategy for localizing fluorophores, photosensitizers, and other small molecule therapeutics inside PFC nanoemulsions.

Concise synthesis of branched fluorous tags for increased fluorous phase solubility

256th National Meeting (2018)

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