Solvent isotope effects normal

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. 

Values of kH olki3. o tend to fall in the range 0.5 to 6. The direction of the effect, whether normal or inverse, can often be accounted for by combining a model of the transition state with vibrational frequencies, although quantitative calculation is not reliable. Because of the difficulty in applying rigorous theory to the solvent isotope effect, a phenomenological approach has been developed. We define <[), to be the ratio of D to H in site 1 of a reactant relative to the ratio of D to H in a solvent site. That is. 

Fig. 5 Variation in kinetic solvent isotope effect, k(H20)/A (D20), for the normal proton-transfer reaction (28)...

The solvent isotope effect has widely been used in distinguishing between whether proton transfer occurs prior to or in the rate-determining step. When proton transfer is the rate determining step, the rate in D20 will be less than in H20. This is a normal primary kinetic isotope effect. However, if there is a fast reversible proton transfer prior to the rate determining step, the reactions occur more rapidly in D20 than in H20. 

A similar analysis applies to CBS mutated tetrachlorohydroquinone dehalo-genase but normal rather than inverse solvent isotope effects are involved. This... 

An S Ar (nucleophilic substitution at aromatic carbon atom) mechanism has been proposed for these reactions. Both nonenzymatic and enzymatic reactions that proceed via this mechanism typically exhibit inverse solvent kinetic isotope effects. This observation is in agreement with the example above since the thiolate form of glutathione plays the role of the nucleophile role in dehalogenation reactions. Thus values of solvent kinetic isotope effects obtained for the C13S mutant, which catalyzes only the initial steps of these reactions, do not agree with this mechanism. Rather, the observed normal solvent isotope effect supports a mechanism in which step(s) that have either no solvent kinetic isotope effect at all, or an inverse effect, and which occur after the elimination step, are kinetically significant and diminish the observed solvent kinetic isotope effect. 

Williams and co-workers provided solvent isotope effect data that supported the mechanism of Scheme 4P The rearrangement of N-phenyl-hydroxylamine (pAl = 1.9) in aqueous H2SO4 exhibits an inverse solvent isotope effect at pH > 2 and a normal solvent isotope effect of 1.5 in the plateau region at pH < 1.0. This is expected for the mechanism of Scheme 4... 

The term solvent isotope effect is used in discussions of equilibrium processes in normal and heavy water for the isotope effect, which is attributed to isotopic substitution of the solvent. Solvent isotope effects may be due primary to differences in the structure constructed by the two isotopic water molecules. 

Deuterium isotope effects on rates of hydrolysis of tetrahydroborate have been examined using the iodate method of analysis. This is valid since exchange of BH4 with water is slow. Hydrolysis of BD4 occurs more rapidly than that of BH4 (kn/ D = 0.70+0.02, 25 The solvent isotope effect is normal,... 

Fig. 5 Variation in kinetic solvent isotope effect, for the normal...

Pepsin catalyzes the hydrolysis of amide bonds of proteins using a unique mechanism in which water attack on the amide is activated by concerted action of two active site aspartyl carboxyl groups. Small normal solvent isotope effects are observed but cannot be unambiguously interpreted regarding their origins and how they relate to proton abstraction from water and/or proton donation to amine leaving group [65]. 

Differences in the rate of mutarotation of sugars in water and in deuterium oxide provide a valuable means for studying mutarotation reactions.135,224,233 237,238 The difference in rates arises from a combination of kinetic and solvent isotope-effects, and is usually expressed as a ratio,knlkD, called the isotope effect. Kinetic isotope-effects are caused by differences in the energy required for alteration of the normal and the isotopic bonds in the corresponding transition states solvent isotope-effects can exist when the isotopic compound is used both as a reactant and as a solvent. 

Hydrolysis of acetals by acid is considered to proceed normally via the A1 mechanism. Electron release in the aldehyde facilitates reaction, the p value being —3.5, indicating stabilization of a cationic intermediate. The solvent isotope-effect k H2O/ D2O is approximately 2.6, which indicates that the acidic property of the solvent is more important than its nucleophilicity. The entropy of activation is positive, 5-20 K l mol-1. Glycopyranosides fit into this generalization, but the acidic hydrolysis of the corresponding furanosides shows negative entropies of activation, indicating a difference in mechanism. 

---