Isotope effect studies

Kinetic data for a number of peresters containing deuterium at the a-position to the acyl group have been reported and are given in Table 105. The kgjkj, values are an average of several measurements and correspond to the actual measured values. 

The secondary isotope effect is consistent with a two-bond homolysis for the peresters listed in Table 105. However, the isotope effect for the perester where R = /-butyl is significantly smaller than for reactions where a /-butyl cation is generated . Although previous data indicate the importance of the ionic structure (II) in the transition state, it appears that a significant contribution from the radical structure (I) occurs as well in the case of R = /-butyl. Carbon isotope effects (ki s/A ), originating from the carboxyl carbon atom, were found to be 0,964 and 0.945 for /-butyl triphenylperacetate and a,a-diphenylperacetate, respectively (ref. 411). The data are consistent with two-bond homolysis. 

---

It is interesting to note that a recent report of a kinetic isotope effects study of cycloaddition of (1) with a nearly symme-... 

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. 

Intramolecular isotope effect studies on the systems HD+ + He, HD+ + Ne, Ar+ + HD, and Kr + + HD (12) suggest that the E l dependence of reaction cross-section at higher reactant ion kinetic energy may be fortuitous. In these experiments the velocity dependence of the ratio of XH f /XD + cross-sections was determined. The experimental results are presented in summary in Figures 5 and 6. The G-S model makes no predictions concerning these competitive processes. The masses of the respective ions and reduced masses of the respective complex reacting systems are identical for both H and D product ions. Consequently, the intramolecular isotope effect study illuminates those... 

While the A1 mechanism shown above operates in most acetal hydrolyses, it has been shown that at least two other mechanisms can take place with suitable substrates. In one of these mechanisms the second and third of the above steps are concerted, so that the mechanism is Sn2cA (or A2). This has been shown, for example, in the hydrolysis of 1,1-diethoxyethane, by isotope effect studies ... 

However, a number of examples have been found where addition of bromine is not stereospecifically anti. For example, the addition of Bf2 to cis- and trans-l-phenylpropenes in CCI4 was nonstereospecific." Furthermore, the stereospecificity of bromine addition to stilbene depends on the dielectric constant of the solvent. In solvents of low dielectric constant, the addition was 90-100% anti, but with an increase in dielectric constant, the reaction became less stereospecific, until, at a dielectric constant of 35, the addition was completely nonstereospecific.Likewise in the case of triple bonds, stereoselective anti addition was found in bromination of 3-hexyne, but both cis and trans products were obtained in bromination of phenylacetylene. These results indicate that a bromonium ion is not formed where the open cation can be stabilized in other ways (e.g., addition of Br+ to 1 -phenylpropene gives the ion PhC HCHBrCH3, which is a relatively stable benzylic cation) and that there is probably a spectrum of mechanisms between complete bromonium ion (2, no rotation) formation and completely open-cation (1, free rotation) formation, with partially bridged bromonium ions (3, restricted rotation) in between. We have previously seen cases (e.g., p. 415) where cations require more stabilization from outside sources as they become intrinsically less stable themselves. Further evidence for the open cation mechanism where aryl stabilization is present was reported in an isotope effect study of addition of Br2 to ArCH=CHCHAr (Ar = p-nitrophenyl, Ar = p-tolyl). The C isotope effect for one of the double bond carbons (the one closer to the NO2 group) was considerably larger than for the other one. ... 

The reaction proceeds via a cyclic TS involving coordination of both the alcohol and ketone oxygens to the aluminum. Computational (DFT) and isotope effect studies are consistent with the cyclic mechanism.190 Hydride donation usually takes place from... 

R. Hille and R.F. Anderson, Coupled electron/proton transfer in complex flavoproteins — solvent kinetic isotope effect studies of electron transfer in xanthine oxidase and trimethylamine dehydrogenase. J. Biol. Chem. 276, 31193-31201 (2001). 

The mechanistic proposal of rate-limiting hydrogen atom transfer and radical recombination is based on the observed rate law, the lack of influence of CO pressure, kinetic isotope effects [studied with DMn(CO)s] and CIDNP evidence. In all known cases, exclusive formation of the overall 1,4-addition product has been observed for reaction of butadiene, isoprene and 2,3-dimethyl-l,3-butadiene. The preferred trapping of allyl radicals at the less substituted side by other radicals has actually been so convincing that its observation has been taken as a mechanistic probe78. 

VI. ISOTOPE EFFECT STUDIES WITH DIENES AND POLYENES. 848... 

A. Carbon-14 and Deuterium Isotope Effect Studies of the Diels-Alder... 

Kopple K, Meyerstein D, Meisel D (1980) Mechanism of the catalytic hydrogen production by gold sols. Hydrogen/deuterium isotope effect studies. J Phys Chem 84 870-875... 

The complexities associated with these reactions were also evident during an intrazeolite product isotope effect study of 2,2,6,6-tetradeutero-l,4-dithiane97 (Fig. 29). The absence of an isotope effect during oxidation with m-chloroperbenzoic is consistent with the lack of C-H(D) abstraction on the reaction surface. The substantial isotope effect of 1.15 + 0.02 for the reaction of singlet oxygen is consistent with the... 

A methodology that has turned out to be a very powerful tool in trying to unravel the intricacies of the mechanism of cytochrome P450-catalyzed oxidation reactions has been the use of deuterium isotope effects. The use of intramolecular deuterium isotope effects have been particularly important in this regard as will be described in chapter 4 where a number of such studies are presented. But, before describing the specific technique that intramolecular isotope effect studies entail, a quick mini review on the nature of deuterium isotope effects is probably in order. 

Korzekwa KR, Trager WF, Nagata K, et al. Isotope effect studies on the mechanism of the cytochrome P-450IIA1-catalyzed formation of delta 6-testosterone from testosterone. Drug Metab Dispos 1990 18(6) 974-979. 

Kinetic isotope effect studies have contributed greatly to our understanding of the details of C-H activation by these types of metal complexes. The simplest energy scheme for kinetic isotope effects is presented schematically in Figure 19.7. 

Abstract A brief introduction deals with the time period from Dalton to the discovery of isotopes by Soddy and Fajans in the early twentieth century which was soon followed by the invention of the mass spectrograph (1922). The next section covers the period from 1922 to the discovery of deuterium by Urey and his colleagues. It includes a discussion of isotope effects in spectroscopy, particularly band spectra of diatomic molecules, and also discusses the discovery of the important stable isotopes in the second row of the periodic table. It ends with the discovery of deuterium, probably the most popular isotope for isotope effect studies. The chapter ends with a short description of the apparatus of theory and experimentation available for isotope effect work at the time of the discovery of deuterium. 

Table 7.5 Isotopomer pairs of lighter elements commonly used in isotope effect studies...

Isotope effect studies using radioisotopes are sometimes convenient. Some elements, fluorine and phosphorus for example, have only one stable isotope, and the determination of isotope effects for them is only possible with radioisotopes. 

Abstract The application of isotope effect studies to problems in geochemistry and geology, meteorology, environmental studies, archeology and paleobotany, food authentication, medical diagnostics and various other practical areas is described using numerous examples. 

We will use reaction 10.15 to illustrate two important concepts of kinetic isotope effect studies. The first concerns the relation between isotope effects of different isotopes of the same element, say D and T. We denote the rate constant of reaction 10.15 by kn and consider isotope effects when one hydrogen in the a-position is substituted by deuterium or tritium ... 

The last parts of this chapter will deal with the so-called mass independent isotope effects which have been rationalized in recent years to be a consequence of unimolecular processes and which have become one of the most fascinating of present day isotope effect studies. 

The disintegration of a substance in a first-order manner. 2. A breakdown of the Swain-Schaad relationship in kinetic isotope effect studies usually as a consequence of tunneling or kinetic complexity. 

---