Rates of proton transfer reactions

Acid-base catalysis appears to be an important factor in virtually all enzymatic reactions. The rates of proton transfer reactions have been well studied in model systems,30 but not during the course of enzyme catalysis. The protonation and deprotonation of acids and bases can be represented as... 

The rates of proton transfer reactions cover a wide spectrum, from exasperatingly slow to diffusion controlled. Any theory which can rationalize this range has obvious merit. Such a rationalization is in fact accomplished, to a large degree, by Br nsted and Pedersen s (1923) relationship between rate (kinetic acidity) and p/sTa (thermodynamic acidity). The relationship, known as the Br0nsted equation, has the form (8) where B is the catalytic rate constant. The... 

Rates of proton transfer reactions 3.1 NORMAL ACIDS... 

THE INFLUENCE OF MOLECULAR STRUCTURE ON RATES OF PROTON-TRANSFER REACTIONS... 

In terms of equation (21) it is possible to give an explanation of the large substituent effect. When protonation of the intermediate is fast compared to decomposition, equation (22) reduces to the usual expression for h/ e- Since the substituent effect for k jk is expected to be small, the observed substituent effect is contained mainly in a/ 4, the rate ratio for C—0 bond breaking and 0—H bond making. Both 3 and 4 should increase with electron donor substituents and 3 would be expected to increase more because the 3 reaction is one bond closer to the substituent than the 4 reaction. Hence the ratio 3/ 4 will increase with electron donation. Maximal and minimal values of kgjk were calculated using various assumptions, as shown in Table 3. From these it can be concluded that the rate constant for proton transfer, step 4, is comparable in magnitude to the rate constant for the breakdown of the tetrahedral intermediate, step 3. Since the rates of proton transfer reactions are... 

The lifetimes of molecules in the lowest excited singlet state are typically of the order of 10 "-10 7 s. Typical rates of proton transfer reactions are 10" s 1 or less. Consequently, excited-state proton transfer may be much slower, much faster, or competitive with radiative deactivation of the excited molecules. 

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

The most obvious differences between solid and liquid acids are in their physical properties. Solids can be heated, which enhances the rate of proton transfer reactions which are slow at room temperature, can be used in solid-liquid and solid-gas reactions and can readily be separated from reactants and products. One of their limitations, however, is that the catalyst can become covered in strongly adsorbed by-product, or at high temperatures by carbonaceous residue, coke , resulting in deactivation. In this case, the utility of the catalyst may ultimately be determined by how readily it can be regenerated. 

This chapter will be concerned mainly with the relation between the equilibrium constants of acid-base reactions and their forward and reverse rates. Relations between equilibrium constants and structure have already been considered in Chapter 6, so that the present discussion also implies relations between rates and structure. Moreover, there are many cases in which rates are easier to measure (though more difficult to interpret) than equilibria and can be compared directly with structures. We shall first consider the general basis and experimental evidence for this type of relation, followed by its molecular interpretation, with special reference to exceptional cases. We have seen in the two preceding chapters that the rates of proton-transfer reactions can be measured either directly, or indirectly through the study of acid-base catalysis, and in the following discussion information from both sources will be used indifferently. 

The lifetimes of molecules in the lowest excited singlet state are typically 10 1 -10 s. Typical rates of proton transfer reactions are <10i°s i. Consequently, excited state proton transfer may be much slower, much faster, or competitive with radiative deactivation of the excited molecules. If excited state proton transfer is much slower than fluorescence, the relative fluorescence intensity will vary with pH exactly the same way as does the absorbance, reflecting only the ground-state acid-base equilibrium. If excited state proton transfer is much faster than fluorescence, the fluorescence intensity will vary with pH in a way that reflects the acid-base equilibrium in the lowest excited singlet state. Equilibrium in the excited state is a rare phenomenon and will not be dealt with further here. 

Since the rate was independent of acidity even over the range where H0 and pH differ, and the concentration of free amine is inversely proportional to the acidity function it follows that the rate of substitution is proportional to h0. If the substitution rate was proportional to [H30+] then a decrease in rate by a factor of 17 should be observed on changing [H+] from 0.05 to 6.0. This was not observed and the discrepancy is not a salt effect since chloride ion had no effect. Thus the rate of proton transfer from the medium depends on the acidity function, yet the mechanism of the reaction (confirmed by the isotope effect studies) is A-SE2, so that again correlation of rate with acidity function is not a satisfactory criterion of the A-l mechanism. 

The occurrence of proton transfer reactions between Z)3+ ions and CHa, C2H, and NDZ, between methanium ions and NH, C2HG, CzD , and partially deuterated methanes, and between ammonium ions and ND has been demonstrated in irradiated mixtures of D2 and various reactants near 1 atm. pressure. The methanium ion-methane sequence proceeds without thermal activation between —78° and 25°C. The rate constants for the methanium ion-methane and ammonium ion-ammonia proton transfer reactions are 3.3 X 10 11 cc./molecule-sec. and 1.8 X 70 10 cc./molecule-sec., respectively, assuming equal neutralization rate constants for methanium and ammonium ions (7.6 X 10 4 cc./molecule-sec.). The methanium ion-methane and ammonium ion-ammonia sequences exhibit chain character. Ethanium ions do not undergo proton transfer with ethane. Propanium ions appear to dissociate even at total pressures near 1 atm. 

The principles outlined above are, of course, important in electro-synthetic reactions. The pH of the electrolysis medium, however, also affects the occurrence and rate of proton transfers which follow the primary electron transfer and hence determine the stability of electrode intermediates to chemical reactions of further oxidation or reduction. These factors are well illustrated by the reduction at a mercury cathode of aryl alkyl ketones (Zuman et al., 1968). In acidic solution the ketone is protonated and reduces readily to a radical which may be reduced further only at more negative potentials. 

Since the rate for the tunneling of a proton is strongly dependent on barrier width, it is necessary that the molecular systems to be studied constrain the distance of proton transfer. Also, since the various theoretical models make predictions as to how the rate of proton transfer should vary with a change in free energy for reaction as well as how the rate constant should vary with solvent, it is desirable to study molecular systems where both the driving force for the reaction and the solvent can be varied widely. 

The overall rate constant for proton transfer will reflect the distribution of the reacting species of the distance R between species. As R decreases, the potential energy barrier in the proton-transfer coordinate decreases leading to an increase in the rate of reaction but at a cost of increasing the energy of the reactant and product states at short distances. The DKL model thus defines the rate of proton transfer as [10]... 

In recent years, there have been numerous studies examining the dynamics of proton transfer within the context of recently developed theoretical models. Reactions in the gas phase, in the solution phase, and in matrices have been examined [59-72]. Few of these studies, however, have addressed the issue of how the rate of proton transfer correlates with the thermodynamic driving force, which is an important correlation for discerning the validity of the various theoretical models. However, there have been two series of investigations by Kelley and co-workers [70, 71], and by Pines et al. [65, 66] that have sought to elucidate the role of solvent dynamics on the rate of proton transfer. 

Both kinetic and thermodynamic data on organometallic hydrides should be very useful. The relative rates of proton transfer processes and other reactions determine a good deal of organometallic chemistry. For example, in our synthesis of cis-0s(C0) (CH )H> reactions 2-4, the comparative rates of... 

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