Kemp elimination reactions proton transfers

Figure 2 Free-energy profile for the Kemp elimination of 5-nitro-benzisoxazole by antibody 4B2. The reaction coordinate for the proton transfer is r(0-H)-r(H-C) with r(0-H)+r(H-C)=2.85 A. Maximum free-energy values are truncated to 30 kcal/mol for clarity.

Enzymes catalyze chemical reaction in aqueous media, but their active sites significantly differ in properties from water. In this chapter, the work on selected chemical reactions with important biological roles is reviewed to assess our current understanding of the effect of the environment that surrounds the reactive species. In particular, simple medium effects such as the ones provided by organic solvents, ionic liquids, and simple micelles are focused on. The findings that led to the computational design of enzymes that catalyze the Kemp elimination, a prototypical proton transfer reaction that has fascinated researchers for more than a century, are discussed. 

The base-catalyzed decomposition of benzisoxazoles to yield 2-cyanophenols (also called the Kemp ehmination. Figure 12) is a reaction that still fascinates researchers, even though it was first reported more than a century ago. The Kemp elimination (an E2 reaction) is not catalyzed by any known natural enzyme but it has been widely used for some time as a prototypical reaction for proton transfer from carbon, and very recently, has been one of the choices, and probably the most successful one (although far from perfect), for the de novo design of enzymes through the aid of computers.Its popularity is certainly facilitated by the ease of preparation of benzisoxazoles from salicylaldehydes, " and by the fact that the... 

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