Proton transfer, linear free energy

Large numbers of reactions of interest to chemists only take place in strongly acidic or strongly basic media. Many, if not most, of these reactions involve proton transfer processes, and for a complete description of the reaction the acidities or basicities of the proton transfer sites have to be determined or estimated. These quantities are also of interest in their own right, for the information available from the numbers via linear free energy relationships (LFERs), and for other reasons. 

It frequently happens that a corner species is derived from a lower energy bond isomer by a proton transfer. The energy of such a proton transfer is calculated from the relevant pvalues, estimated where necessary by linear free energy relations.96... 

If a proton-transfer reaction is visualized as a three-body process (Bell, 1959b), a linear free energy relationship is predicted between the acid dissociation constant, Aha, and the catalytic coefficient for the proton-transfer reaction, HA. Figure I shows the relationships between ground-state energies and transition-state energies. This is a particular case of the Bronsted Catalysis Law (Bronsted and Pedersen, 1924) shown in equation (9). The quantities p and q are, respectively, the number of... 

Warshel, A., Hwang, J-K and Aqvist (1992) Computer simulations of enzymatic reactions examination of linear free-energy relation ship and quantum-mechanical corrections in the initial proton-transfer step of carbonic anhydryse, Farad. Dissc. 93, 225-238. 

This relation between variable isotope effects with a maximum and plausibly non-linear free energy relation was qualitatively noted in connection with proton transfers Lewis,... 

The interest in proton transfer to and from carbon arises partly because this process occurs as an elementary step in the mechanisms of a number of important reactions. Acid and base catalysed reactions often occur through intermediate carbonium ions or carbanions which are produced by reactions (1) and (2). A knowledge of the acid—base properties of carbonium ions or carbanions may also help in understanding reactions in which these species are present as reactive intermediates, even when they are generated by processes other than proton transfer. Kinetic studies of simple reactions such as proton transfer are also important in the development of theories of kinetics. Since both rates and equilibrium constants can often be measured for (1) and (2) these reactions have been useful in the investigation of correlations between rate coefficients and equilibrium constants (linear free energy relations). 

The EVB potential was calibrated to reproduce experimental data for the uncatalyzed reference reaction in solution. In the case of proton transfer the difference in free energy between the two states, zlG° can be obtained from the difference in pK between the donor and acceptor. Once AG° is known the activation energy AG can be determined from a linear free energy relationship compiled by Eigen [50]. For the proton transfer described by 0,->[Pg.272]

Linear free energy relationships are particularly useful if it is necessary to have accurate knowledge of the pA of an intermediate which is unstable, or for which other experimental difficulties such as solubility prevent its experimental determination. Information about the values of putative intermediates is essential in mechanistic studies of reactions where proton transfers are involved. ... 

J., Computer Simulations of Enzymatic Reactions Examination of Linear Free-Energy Relationships and Quantum-Mechanical Corrections in the Initial Proton-transfer Step of Carbonic Anhydrase, Faraday Discuss. 1992, 93, 225. 

A prerequisite that the mechanism in a series should be the same is a linear free-energy correlation if a member of the series takes a different pathway then the alternative mechanism will be more favourable, will predominate over the normal and will be diagnosed as a positive deviant point. An example of this behaviour is the demonstration that general acid catalysis by primary amines of the iodination of acetone differs from that by carboxylic acids (Fig. 24) [3a] simple proton transfer is identified with the carboxylic acid catalysis and it is thought that amines utihse Schiff s base formation (Eqn. 116) leading to a more favourable path. 

Heavy-atom isotope effects have been used to examine the transition state structures of the first phosphoryl transfer step, formation of the phosphocysteine intermediate, with the PTPs PTPl and YopH, and the DSP VHR (78). For each it was found that the transition state is very loose, resembling uncatalyzed phosphoryl transfer, and with full neutralization of the leaving group by proton transfer from the conserved aspartic acid. The transition state of the second chemical step, dephosphorylation of the intermediate, was probed in Stpl using linear free energy relationships and was found to proceed with little nucleophilic participation, suggesting that a loose transition state is operative for this reaction as well (79). 

---