Reactions involving single proton transfer

The results of the above analysis of reactions involving two proton transfers may be compared with those for reactions in which only a single transfer is kinetically relevant (Sec. III.3.a). For a single transfer the existence of an equilibrium between catalyst and substrate always produces the appearance of specific catalysis by hydrogen or hydroxyl ions, and the detection of general acid-base catalysis therefore excludes... 

In the above treatment it has been assumed that the ions (HRH)+ and Br exist in the free state, as they undoubtedly do in aqueous solution. However, solvents which are aprotic, e.g., hydrocarbons, normally have such low dielectric constants that the majority of ions present will exist at least as ion pairs, and partly as larger aggregates. This circumstance may well affect the kinetics. For a reaction involving only a single proton transfer the concentration of ion pair will be directly proportional to the concentrations of catalyst and substrate, so that the kinetics will be simpler than when free ions are present. On the other hand, in reactions involving two proton transfers, if the first product of... 

Similar considerations apply to reactions involving two proton transfers in aprotic solvents. If the first step is rate-determining, the problem reduces to a single proton transfer. When the second step is ratedetermining, the assumption of free ions leads to the same prediction as in aqueous solution, since the composition of the transition state is still equivalent to one molecule of substrate plus one molecule of acid, and this remains true even if the ions HSH and B" are associated in a pair. However, the ion pair initially formed in the first proton transfer may well have a configuration which is unfavourable for the second proton transfer, which involves the removal of a proton from a different atom. This raises the possibility that the second proton transfer may involve another basic... 

Whereas the mechanism of the C2-H deprotonation of ThDP has been shown to be identical in all ThDP-dependent enzymes investigated, the following steps in catalysis of the different enzymes require different protonation and deprotonation reactions of the intermediates formed along the process. In order to identify side chains involved in proton transfer steps, the distribution of reaction intermediates during catalysis of any wild type enzyme can be compared with that of active site mutant enzymes. Rate constants for single steps in catalysis can be calculated from... 

Consider acid catalysis of a reaction involving only a single proton transfer, which we can write as... 

Catalysis by some, if not all, of these enzymes appears to involve intramolecular proton transfers mediated by a single active site base. In the case of the trypto-phanase reaction, an intramolecular 1,3-proton transfer takes place between C-2 of tryptophan and C-3 of the indol leaving group, on the basis of significant tritium transfer between these two carbons using (2S)-[2- H]tryptophan as substrate (277). This is consistent with a single active site base catalyzing a supra-facial proton transfer with respect to the putative aminoacrylate intermediates [Eq. (55)] ... 

Solvent kinetic isotope effects (SKIEs) in H2O/D2O mixtures on the reaction of /)NPP catalyzed by calcineurin gave a small normal value of 1.35. Proton inventory and fractionation data are consistent with a mechanism involving a single proton transfer from a metal-bound water, although due to the small KSIE value and the inherent experimental error of the proton inventory technique, the participation of a second proton could not he excluded. Further information has been furnished by heavy-atom isotope effects. Reaction of NPP catalyzed by APP shows that phosphoryl transfer is fully rate limiting. However, for calcineurin the... 

See Figure 18.19 in the text. Molecular O2 is bound between the Fe " and Cu" ions of the heme a3-CuB center of cytochrome oxidase. The oxygen remains bound whife four electrons and four protons are sequentially added to its various intermediates, resulting in the net release of two H2O. The heme u-Cua center suppfies the efectrons for this process. Although four electrons are used in the reduction of O2 to 2 H2O, the individ-uaf steps of the reaction cyde involve single electron transfers. 

We shall treat first base-catalysed reactions involving a single proton transfer, which probably constitute the most important class of reactions, and initially only aqueous solutions will be considered. For a substrate SH the sequence of reactions is... 

Provided that the acid-base composition of the solution remains constant during a reaction, the kinetics can again be described by three first-order constants /c, i, and /c2> of which will now depend upon the concentrations of the acids and bases present. A kinetic analysis can be carried out just as for reactions involving a single proton transfer, with the following results ... 

If the reaction involves only a single proton transfer, the kinetic scheme is as before... 

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