Catalysis, acid-base energetics

Electronically excited states of organic molecules, acid-base properties of, 12,131 Energetic tritium and carbon atoms, reactions of, with organic compounds, 2, 201 Enolisation of simple carbonyl compounds and related reactions, 18,1 Entropies of activation and mechanisms of reactions in solution, 1,1 Enzymatic catalysis, physical organic model systems and the problem of, 11, 1 Enzyme action, catalysis of micelles, membranes and other aqueous aggregates as models of, 17. 435... 

The chemical reaction catalyzed by triosephosphate isomerase (TIM) was the first application of the QM-MM method in CHARMM to the smdy of enzyme catalysis [26]. The study calculated an energy pathway for the reaction in the enzyme and decomposed the energetics into specific contributions from each of the residues of the enzyme. TIM catalyzes the interconversion of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (GAP) as part of the glycolytic pathway. Extensive experimental studies have been performed on TIM, and it has been proposed that Glu-165 acts as a base for deprotonation of DHAP and that His-95 acts as an acid to protonate the carbonyl oxygen of DHAP, forming an enediolate (see Fig. 3) [58]. 

Catalysis in homogeneous solution has already been referred to (p. 41) as operating by making available an alternative reaction path of lower energetic demand, often via a new and more stable (lower energy) intermediate by far the most common, and important, catalysts in organic chemistry are acids and bases. 

Since the products are the same chemical species as the reactants, the over-all reaction is substantially thermoneutral except for activation energy, the problem of energetics is thus side-stepped. The apparent ter-molecular reaction required by Eq. (43) is also no problem, as the dissolved molecules are essentially in constant collision with water molecules. Wilmarth, Dayton, and Flournoy questioned the adequacy of this concerted attack mechanism, however, as they believed that it would predict acid catalysis of the exchange reactions, as well as base catalysis. 

In this chapter, we will look at some of the most common catalysts— nucleophilic catalysts, acid catalysts, base catalysts, and metal-ion catalysts—and the ways in which they provide an energetically more favorable pathway for an organic reaction. We will then see how the same modes of catalysis are used in enzyme-catalyzed reactions. 

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