Proton transfer, preassociation

The preassociation mechanism is more efficient than the trapping mechanism because it generates an intermediate which immediately reacts by an ultrafast proton transfer (in the pre-association complex, Int) and thus avoids the diffusion-controlled step bringing the catalyst and intermediate together. This mechanism is sometimes called a spectator mechanism because, although the catalyst is present in the transition structure, it is not undergoing any transformation [10]. 

Fig. 8 Potential mechanisms for hydrolysis of phosphomonoester monoanions. In mechanism (a), proton transfer from the phosphoryl group to the ester oxygen (probably via the intermediacy of a water molecule) yields an anionic zwitterion intermediate. This may react in either concerted fashion (upper pathway) or via a discrete metaphosphate intermediate in a preassociative mechanism (bottom pathway). Mechanism (b) denotes proton transfer concerted with P-O(R) bond fission. As with (a), such a mechanism could either occur with concerted phosphoryl transfer to the nucleophile (upper pathway) or via a discrete metaphosphate intermediate in a preassociative mechanism (bottom pathway).

Dn + An, etc.) recommended by IUPAC, which, though, for important reactions is given in a foortnote. The Jencks-Guthrie system is in my view superior, as it can indicate preassociation reactions and proton transfers, which are particularly important in carbohydrate chemistry, in a way that the older Ingold system cannot, but unfortunately in the 15 years since its formulation, the Jencks-Guthrie system has not found widespread acceptance. 

When the rate-limiting step of a reaction such as that of Eqn. 7 is the diffusion-controlled encounter of two reagents an enzyme may increase the rate simply by having the nucleophile and catalyst preassociated i.e. they do not have to diffuse through solution before reaction can occur. This situation occurs [3] in simple intermolecular reactions when the rate of breakdown of the intermediate to regenerate reactants is faster than the rate of separation of the intermediate and catalyst, 10 -10"/sec, and when proton transfer between the intermediate and catalyst is thermodynamically favourable. The formation of the intermediate must take place by a preliminary association of the reactants and catalyst (Eqn. 9 and Fig. 3). 

The rate enhancement obtainable by preassociation compared with trapping is given by the ratio of the rate of breakdown of the intermediate I to generate reactants to the rate of dissociation of the intermediate and catalyst I.C. (Fig. 3). The maximum lowering of the free energy of activation obtainable is the activation energy for diffusion of apart of the catalyst and intermediate i.e. ca. 15 kJ/mole, a rate enhancement of ca. 400. There can be no rate advantage from a preassociation mechanism when the proton transfer is thermodynamically unfavourable. 

A number of mechanistic pathways have been identified for the oxidation, such as O-atom transfer to sulfides, electrophilic attack on phenols, hydride transfer from alcohols, and proton-coupled electron transfer from hydroquinone. Some kinetic studies indicate that the rate-determining step involves preassociation of the substrate with the catalyst.507,508 The electrocatalytic properties of polypyridyl oxo-ruthenium complexes have been also applied with success to DNA cleavage509,5 and sugar oxidation.511... 

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