Organocatalysis in aqueous media

Even though enzymes are the cornerstones of living systems, it has so far proven difficult to deploy artificial catalysts in a biological setting. Organocatalysts are arguably well-suited artificial catalysts for this purpose because, compared with enzymes and inorganic catalysts, they are simpler, often less toxic and widely accessible. This Review describes how organocatalysts that operate in aqueous media might enable us to selectively access new chemical transformations and provide new possibilities for chemical biology and biomedicine. Organocatalysts can be categorized according to the mechanisms by which they activate substrates, drawing comparisons with enzymes. We describe the characteristics of a catalyst that are necessary for biological compatibility and in vivo applicability, and use these to evaluate a selection of organocatalytic reactions. The attributes of the catalyst (such as functional groups and pKa values) and the reaction (such as the microenvironment surrounding intermediates) are key considerations when developing efficient organocatalysis in aqueous media. Although we only know of a limited set of organocatalytic reactions with biological potential, on the basis of recent developments we expect a bright future for organocatalysis in biology, to the benefit of chemical biology and biomedicine. The application of organocatalysis in biology is still in its infancy. In this Review, we evaluate organocatalytic reactions in terms of their applicability in biological settings, including new technologies in chemical biology and biomedicine.