Fluoroalcohols for chemical modification of biomolecules

While their broad utility in various chemistry fields were well recognized for decades, fluoroalcohols have recently emerged as a unique solvent system for bioconjugation development. This review describes examples and roles of fluoroalcohols such as trifluoroethanol (TFE) and hexafluoroisopropanol (HFIP) for chemical modification of biomolecules such as polypeptides, nucleic acids, and saccharides. Many chemical modification processes were facilitated by notable functions of those fluoroalcohols such as a proton shuttle, reversible adduct formation with reactive species, and compatibility with electrochemistry/photochemistry. The usefulness of the fluoroalcohol solvents can be even promoted by its combination with a different solvent system for reaction enhancement and protein stabilization. The collection of the various chemical transformations in this review is an indication of the rapid growth of the solvent-assisted bioconjugation field.