The Deuterium Isotope Effect

Wiberg, Kenneth B.

doi:10.1021/cr50004a004

Cited by 709 publications

(348 citation statements)

References 92 publications

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“…4 using the measured values for D2O K V app = ðH=DÞ ð1:6 ± 0:5Þ, D2O V 0 ð1:8 ± 0:2Þ, and D2O « V rad ð0:22 ± 0:03Þ to give the result D2O k 9 = 13 ± 4. This isotope effect is at the upper limit of the semiclassic expectation for a primary deuterium KIE (45). It is therefore incompatible with the predicted large internal forward commitment due to irreversible electron transfer preceding deprotonation of the resulting protonated ketone.…”

Section: +1mentioning

confidence: 77%

EPR-kinetic isotope effect study of the mechanism of radical-mediated dehydrogenation of an alcohol by the radical SAM enzyme DesII

Ruszczycky

Choi

Liu

2013

Proc. Natl. Acad. Sci. U.S.A.

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The radical S-adenosyl-L-methionine enzyme DesII from Streptomyces venezuelae is able to oxidize the C3 hydroxyl group of TDP-D-quinovose to the corresponding ketone via an α-hydroxyalkyl radical intermediate. It is unknown whether electron transfer from the radical intermediate precedes or follows its deprotonation, and answering this question would offer considerable insight into the mechanism by which the small but important class of radical-mediated alcohol dehydrogenases operate. This question can be addressed by measuring steady-state kinetic isotope effects (KIEs); however, their interpretation is obfuscated by the degree to which the steps of interest limit catalysis. To circumvent this problem, we measured the solvent deuterium KIE on the saturating steady-state concentration of the radical intermediate using electron paramagnetic resonance spectroscopy. The resulting value, 0:22 ± 0:03, when combined with the solvent deuterium KIE on the maximum rate of turnover (V) of 1:8 ± 0:2, yielded a KIE of 8 ± 2 on the net rate constant specifically associated with the α-hydroxyalkyl radical intermediate. This result implies that electron transfer from the radical intermediate does not precede deprotonation. Further analysis of these isotope effects, along with the pH dependence of the steady-state kinetic parameters, likewise suggests that DesII must be in the correct protonation state for initial generation of the α-hydroxyalkyl radical. In addition to providing unique mechanistic insights, this work introduces a unique approach to investigating enzymatic reactions using KIEs.T he enzyme-catalyzed dehydrogenation of an alcohol to a carbonyl is one of the most common and fundamental reactions of both primary metabolism and secondary metabolism. In the majority of cases studied, these reactions proceed via hydride transfer to an organic cofactor, such as the nicotinamide moiety of NAD(P) + or the isoalloxazine group of FAD among others (1, 2). In contrast, much less is understood regarding radical-mediated dehydrogenation of an alcohol, because only a handful of enzyme examples have been described. Of the radical alcohol dehydrogenases, galactose oxidase is the most extensively studied, and it is known to use a Cu II ion coordinated to a proteinderived 3′-(S-cysteinyl)tyrosyl radical to catalyze dehydrogenation of the C6 hydroxyl group of galactose (3, 4). In contrast, BtrN and the anaerobic sulfatase maturating enzymes (anSMEs) are radical S-adenosyl-L-methionine (SAM) enzymes (5-7) responsible for the dehydrogenation of the C3 hydroxyl group of 2-deoxy-scylloinosamine (8, 9) and the hydroxyl/sulfhydryl moieties of serine/ cysteine residues (10-12), respectively. In addition to the primary [4Fe-4S] 1+ cluster, which reduces SAM (1) to methionine (2) and the 5′-deoxyadenosyl radical (17; see Fig. 4) to initiate radical catalysis, BtrN (13,14) and anSMEs (15-18) possess one or more auxiliary [4Fe-4S] aux clusters, which have been proposed to coordinate the hydroxyl group to be oxidized in the substrate.The enzyme...

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Section: +1mentioning

confidence: 77%

EPR-kinetic isotope effect study of the mechanism of radical-mediated dehydrogenation of an alcohol by the radical SAM enzyme DesII

Ruszczycky

Choi

Liu

2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Moreover, even the smallest changes of the attractive interactions has a visible impact on the selectivity, as was demonstrated by the use of the Zn (tetrakis-(pentadeuterophenyl)-porphyrin) (ZnTPP-D 20 , entry 13). The subtle size differences between the pentaprotophenyl and the pentadeuterophenyl groups, as well as different polarizabilities of the C-1 H and C-2 H bonds [28][29][30][31][32] , both contribute to the weakening of the CH-p attractions, resulting in the selectivity dropping from 91% (with ZnTPP) to 70% (with ZnTPP-D 20 , entries 6 and 13, respectively). This example highlights the importance of the weak interactions between the porphyrin building blocks of the capsule, contributing to the reorganization energy and hence the selectivity of the enclosed transition metal catalyst.…”

Section: Formation Of Capsulesmentioning

confidence: 99%

Capsule-controlled selectivity of a rhodium hydroformylation catalyst

et al. 2013

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Chemical processes proceed much faster and more selectively in the presence of appropriate catalysts, and as such the field of catalysis is of key importance for the chemical industry, especially in light of sustainable chemistry. Enzymes, the natural catalysts, are generally orders of magnitude more selective than synthetic catalysts and a major difference is that they take advantage of well-defined cavities around the active site to steer the selectivity of a reaction via the second coordination sphere. Here we demonstrate that such a strategy also applies for a rhodium catalyst; when used in the hydroformylation of internal alkenes, the selectivity of the product formed is steered solely by changing the cavity surrounding the metal complex. Detailed studies reveal that the origin of the capsule-controlled selectivity is the capsule reorganization energy, that is, the high energy required to accommodate the hydride migration transition state, which leads to the minor product.

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“…The proposed Scheme 3 and the derived rate law (17) the greater basicity of OD − as compared to OH − [27,28] In the present investigation, a plot of (k 0 /k n ) 1/2 versus n is found to be linear (r = 0.9954) with a slope (Φ j − 1)=−0.27 for which Φ j of OH − is 0.73. There is a good agreement between the present value and the values reported for the fractionation factor of OH − ion [31][32][33][34].…”

Section: Mechanism and Rate Law Of Os(viii) Catalyzed Oxidation Of Bimentioning

confidence: 54%

“…The [27,28]. In the present case, the observed solvent isotope effect is greater than unity, which is due to the greater basicity of OD − compared to OH − .…”

Section: Mechanism and Rate Law Of Uncatalyzed Oxidation Of Biotinmentioning

confidence: 60%

Os(VIII)-catalyzed and uncatalyzed oxidation of biotin by chloramine-T in alkaline medium: Comparative mechanistic aspects and kinetic modeling

Ramalingaiah

Jagadeesh

Puttaswamy

2007

Journal of Molecular Catalysis A: Chemical

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Sodium N-chloro-p-toluenesulfonamide (chloramine-T or CAT) is the prominent member of aromatic sulfonyl haloamines and has received considerable attention as a mild oxidant for several organic compounds. d-Biotin, a member of the B-vitamin family, is an essential nutrient in human nutrition as is commonly referred to as Vitamin H. Controlled oxidation of biotin to biotin sulfoxide forms a very important synthetic route in biochemical reactions. Optimum conditions have been developed for the oxidation of biotin to biotin sulfoxide. Literature survey has revealed that no attention has been paid towards the controlled oxidation of biotin to biotin sulfoxide by N-haloamines from the kinetic and mechanistic view points. This prompted us to undertake the title investigation. The kinetics of Os(VIII) catalyzed and uncatalyzed oxidation of biotin by CAT have been studied in NaOH medium at 303 K under identical experimental conditions. The stoichiometry (1:1) and the oxidation product (biotin sulfoxide) are the same for Os(VIII) catalyzed and uncatalyzed reactions. Biotin sulfoxide was confirmed by GC-MS analysis. In Os(VIII) catalyzed oxidation, the rate law is [Biotin] x /[NaOH] −y for uncatalyzed reaction, where x and y are less than unity. The reaction was subjected to changes in: (a) concentration of added reduction product of CAT, p-toluenesulfonamide, (b) ionic strength, (c) dielectric permittivity and (d) halide ions effect in both the cases. Proton inventory studies made in a mixture of H 2 O-D 2 O indicated the participation of OH − ion in the formation of transition state. The reaction fails to initiate polymerization of acrylonitrile. Activation parameters for the composite reaction were deduced from Arrhenius plots. In case of uncatalyzed reactions, the reaction constants involved in the proposed scheme were deduced. Under the identical set of experimental conditions, the kinetics of Os(VIII) catalyzed oxidation of biotin by CAT in alkaline medium has been compared with uncatalyzed reactions, revealing that the catalyzed reactions are eight fold faster than the uncatalyzed reactions. Hence, Os(VIII) acts as an efficient catalyst for the oxidation of biotin by CAT in alkaline medium. The catalytic constant (K C ) has been calculated at different temperatures and the values of activation parameters with respect to catalyst have been evaluated from the plots of log K C versus 1/T. Some spectroscopic evidence for the formation of 1:1 complex between oxidant and Os(VIII) has been obtained. CH 3 C 6 H 4 SO 2 NHCl has been postulated as the reactive oxidizing species in both the cases. The observed experimental results have been explained by plausible mechanisms and the related rate laws have been deduced for both catalyzed and uncatalyzed reactions.

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The Deuterium Isotope Effect

Cited by 709 publications

References 92 publications

EPR-kinetic isotope effect study of the mechanism of radical-mediated dehydrogenation of an alcohol by the radical SAM enzyme DesII

EPR-kinetic isotope effect study of the mechanism of radical-mediated dehydrogenation of an alcohol by the radical SAM enzyme DesII

Capsule-controlled selectivity of a rhodium hydroformylation catalyst

Os(VIII)-catalyzed and uncatalyzed oxidation of biotin by chloramine-T in alkaline medium: Comparative mechanistic aspects and kinetic modeling

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