Proton-Transfer Rates in Solution

The protolysis of acids of similar strength spans an extraordinary range of reaction rates. For example, the rate of the acid catalysed dedeuteration of azulene-l-rf (pAT, = 1.76) is 0.45 sec [20], whereas the deprotonation rate of electronically excited 5-cyano-l-naphthol (pA),= 2.8) is 1.3X10 sec [21], when both of them are measured in water (p/fj,= -1.74). The nature of the reactants also has a profound effect on the kinetic isotope 

In the remainder of this chapter, the rates of PT reactions in solution are quantitatively related to the molecular structures of the reactants and to their hydrogen-bonding ability. This relation uses the ISM, previously employed to calculate the rates of atom transfers and S 2 reactions, thus providing a general account of the rates of the most important bond-breaking-bond-making reactions. In the next chapter, the principles applied to these reactions in gas phase and in solution are also applied to some cases of enzyme catalysis. 

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Borgis, D. and Hynes, J. T. Dynamical theory of proton tunneling transfer rates in solution general formulation, Chem. Phys., 170(1993),315-346... 

Kinetic Acidities in the Condensed Phase. For very weak acids, it is not always possible to establish proton-transfer equilibria in solution because the carbanions are too basic to be stable in the solvent system or the rate of establishing the equilibrium is too slow. In these cases, workers have turned to kinetic methods that rely on the assumption of a Brpnsted correlation between the rate of proton transfer and the acidity of the hydrocarbon. In other words, log k for isotope exchange is linearly related to the pK of the hydrocarbon (Eq. 13). The a value takes into account the fact that factors that stabilize a carbanion generally are only partially realized at the transition state for proton transfer (there is only partial charge development at that point) so the rate is less sensitive to structural effects than the pAT. As a result, a values are expected to be between zero and one. Once the correlation in Eq. 13 is established for species of known pK, the relationship can be used with kinetic data to extrapolate to values for species of unknown pAT. 

The rates of proton transfer reaction in solutions and proteins are determined by the corresponding rate constants (e.g. Ref [3]). 

The details of proton-transfer processes can also be probed by examination of solvent isotope effects, for example, by comparing the rates of a reaction in H2O versus D2O. The solvent isotope effect can be either normal or inverse, depending on the nature of the proton-transfer process in the reaction mechanism. D3O+ is a stronger acid than H3O+. As a result, reactants in D2O solution are somewhat more extensively protonated than in H2O at identical acid concentration. A reaction that involves a rapid equilibrium protonation will proceed faster in D2O than in H2O because of the higher concentration of the protonated reactant. On the other hand, if proton transfer is part of the rate-determining step, the reaction will be faster in H2O than in D2O because of the normal primary kinetic isotope effect of the type considered in Section 4.5. 

Proton exchange rates in aqueous solutions are enhanced by small amounts (0.5% V/V) of hydrophobic substances (e.g., methanol, dioxane) because of a consequent increase in H-bonded water structure in the hydration shells through which the proton transfer is mediated (9). 

Table IV is an attempt to summarize the results of these proton transfer studies in nonaqueous solvents. There is no systematic trend in what seems to be the rate limiting step in contrast to the attractive Eigen-Wilkins generalization for the mechanism of metal ion complexation. Obviously, many more proton transfer kinetic studies in nonaqueous solutions are needed for beautiful generalizations to emerge. Whether investigators will have the patience to carry them out or not is the only uncertainty.

Line shape analysis of the proton transfer in THF gave A// =4.5 kcalmol 1 and AS = -21 eu. Actually, the proton transfer rate depends critically on solvent. It is slow in diethyl ether-<7 0. Adding up to 2 mol% THF-d8 to the ether solution, the rate is first order in THF-r/g- However, above the latter I I IL -z/g concentration the kinetic order in THF- 8 increases. Faster transfer in the presence of superior ligands for lithium in conjunction with the large negative entropy of activation implies that development of the transition state involves increased solvation around Li+. In principle, that should facilitate transfer of lithium between two ends of the bridge. 

Delpuech and co-workers [190] have begun a comparative study of proton transfer behaviour for amines in water and dimethylsulphoxide using NMR methods. Proton transfer rates for amines in aqueous solution were originally studied using NMR [10, 191]. It is found [190] that rate coefficients for reaction (108)... 

A large number of proton-transfer reactions in dilute aqueous solutions are found to have rate constants close to those predicted by the diffusion model. For example, consider the following proton transfers and the observed rate... 

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