Synthesis of fluorinated NAD as a soluble coenzyme for enzymatic chemistry in fluorous solvents and carbon dioxide

The synthesis of the coenzyme nicatinamide adenine dinucleotide (NAD) with an covalently attached fluorinated polymer is reported. The fluorinated NAD (FNAD) was rendered soluble in both fluorous solvents and liquid carbon dioxide due to the attachment of a perfluoropolyether. The enzyme horse liver alcohol dehydrogenase (HLADH) was active in catalyzing oxidation/reduction reactions using FNAD as a soluble coenzyme in a fluorous solvent, methoxynonafluorobutane (HFE), and liquid carbon dioxide. In both solvents, the activity of HLADH using FNAD was greater than the same molar amount of unmodified (insoluble) NAD, indicating that a soluble coenzyme results in more efficient reactions.