Deuterium isotope effects isomerization

Saunders M, Jaffe MH, Vogel P (1971) A new method for measuring equilibrium deuterium isotope effects. Isomerization of 3-deuterio-2,3-dimethylbutyl-2-ium ion. J Am Chem Soc 93 2558-2559... 

The rates of hydration of substituted phenylpropiolic acids give a rho of —4.77 when plotted against a, comparable to Ihe acid-catalyzed isomerization of czs-cinnamic acid, with a rho value of —4.3. The solvent deuterium isotope effects are 3.7-S.2 for the isomerization of cinnamic acids at... 

Yang has observed that cis-trans isomerization of 3-methyl-2-pentenes is accompanied by oxetane formation and concluded that intermediates such as (22) are common to both isomerization and oxetane formation/825 Deuterium isotope effects are also consistent with the involvement of this type of intermediate/83,845 ... 

For an elegant study of the secondary deuterium isotope effects on a non-Schenck sensitized cis-trans isomerization, see Refs. 85-87. 

In 1895, Emil Ficher proposed an enediol intermediate for this isomerization. As would be expected, the enzyme-catalyzed isomerization of glucose-6-phosphate in 2H20 is accompanied by incorporation of deuterium into the product fructose 6-phosphate at C-l. In the reverse reaction 2H-containing fructose 6-phosphate was found to react at only 45% of the rate of the 1H-containing compound. Thus, the primary deuterium isotope effect expected for a rate-limiting cleavage of the C-H bond was observed (see Chapter 12, Section B,3). 

To supplement the data on prolyl isomerization, I will draw on the literature describing rotation about the C-N bond in secondary amides. Early studies in this field were described by Stewart and Siddall in an excellent 1970 review. As we will see, these reactions are related to prolyl isomerization and support the mechanism to be proposed for prolyl isomerization. The mechanism is based on results from a variety of experimental approaches. In all cases, experiments employing kinetic-based probes will be used to obtain an accurate picture of the activated complex in the rate-limiting transition state. The experiments that will be described include thermodynamics, in which activation parameters (i.e., AG, AHt, and ASt) will be described solvent effects, in which the influence of organic solvents and deuterium oxide will be reviewed acid-base catalysis substituent effects and secondary deuterium isotope effects. 

Two types of solvent effects have been determined for prolyl isomerization and amide rotation (1) the effect of solvent deuterium on reaction rate and (2) the effect of organic solvents on reaction rate. Solvent deuterium isotope effects are useful tools in probing the role of proton transfer... 

The single most revealing mechanistic parameter for prolyl isomerization and amide rotation is the secondary deuterium isotope effect. In general for such studies, the hydrogens on the carbon that is bonded to the carbonyl carbon of the amide or imide (the /3-hydrogens ) are substituted with deuterium and reaction rate constants are measured for... 

Secondary deuterium isotope effects have been measured for the cis-to-trans prolyl isomerization of Suc-Ala-Gly-cis-Pro-Phe-pNA (where pNA is p-nitroanilide) and C-N rotation in DMA. In the former case, the isotope effect for the two hydrogens of glycine is 1.05 0.02 (Fischer et al., 1989a Harrison et ai, 1990 Harrison and Stein, 1990a), and for C—N rotation in DMA, the isotope effect for the three hydrogens of the acetyl moiety is 1.10 0.05. Significantly, the effect for two deuteriums in DMA can be calculated to be 1.05 (Fujihara and Schowen, 1985). 

The deuterium isotope effect was examined in the hope that it might provide some clue as to the mechanism of vinylic mercaptan formation. The lack of any significant isotope effect precludes any choice between insertion and isomerization since either mechanism would be consistent with the finding. 

The dehydration reaction shows a normal kinetic deuterium isotope effect indicating loss C2 proton as the rate-determining step. This fits with fast protonation at oxygen followed c formation of the same cation with the rest of the mechanism the same. The dehydration is I than the isomerization so loss of water is faster than protonation of the alkene. We have... 

Amimoto, K., Kanatomi, H., Nagakari. A., Fukuda, H., Koyama, H. and Kawato, T. (2003) Deuterium isotope effect on the solid-state thermal isomerization of photo-coloured ds-keto spedes of N-salicylideneaniline. Chem. Commun., 870-871. 

Similar studies of the enzyme from pig skeletal muscle have been reported 175,183). In the earlier work, a fast burst of NADH formation in the dead-time of the apparatus was observed, equal in amplitude to the active center concentration at pH 8.0, but smaller at lower pH values. The suggestion that slow isomerization of the ternary product complex before pyruvate release may be the step responsible for the low steady-state maximum rate of lactate oxidation seems to be inconsistent with the full burst observed at pH 8.0, since it might be expected to result in partial equilibration of the reactant and product ternary complexes. Direct studies of the oxidation of E-NADH by pyruvate at pH 9.0 did indicate that reverse hydride transfer from NADH to pyruvate is indeed fast, but the absence of a deuterium isotope effect suggested that the observed rate constant of 246 sec, equal to the maximum steady-state rate of pyruvate reduction, may reflect an isomerization of the ternary complex preceding even faster hydride transfer. More recent studies 183) with improved techniques, however, appear to indicate no burst of enzyme-bound NADH formation preceding the steady-state phase of lactate oxidation at pH 8.0. On the basis of stopped-flow studies of lactate oxidation in the presence of oxamate, which forms a dead-end complex with E-NADH and can serve as an indicator of the rate of formation... 

The entropy of activation for isomerization of allyl thionbenzoate, — 10 eu, is similar to entropies of activation for other cyclic, concerted allylic iso-merizations. Additional support for a concerted mechanism is provided by secondary deuterium isotope effects on the rate of isomerization of allyl thionbenzoate. Each a-deuterium atom lowers the isomerization rate by about 6%, while each y-deuterium atom increases the rate by about 3%. Since allylic reactions which proceed by carbonium ion, carbanion, and radical pathways are known to be retarded by about twice as much for each a-deuteron, while an allylic chloride solvolysis exhibited a y deuterium isotope effect of zero, the observed secondary isotope effects provide support for a concerted process whose transition state has little carbonium ion, carbanion, or radical character. 

Subsequent work with deuterated exomethylene materials established that the products were formed with a substantial normal secondary deuterium isotope effect 1.30), but the geometric isomerization of the starting material had... 

Let us take the Ordered Bi Bi mechanism depicted in Fig. 3 this time, we refer to an enzymatic reaction in which the isomerization of both central complexes, EAB and EPQ, takes place. The family of deuterium isotope effects on a chemical reaction following this mechanism is illustrated in Fig. 3. 

---