Reaction-coordinate tunneling in hydride-transfer reactions

Huskey, W. Phillip; Schowen, Richard L.

doi:10.1021/ja00355a038

Cited by 138 publications

(157 citation statements)

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“…Finally, in accordance with the ensemble-averaged variational transition state theory (VTST) results from Truhlar, Gao, and co-workers (24,25), the model supports the recently articulated hypothesis that the inflated mSSEs reported for many ADHs since 1989 result from deflated 2°D/T KIEs because of the shorter donor-acceptor distance (DAD) required for D transfer (1,34). The present model mirrors some of the previous empirical calculations on ADH and other systems (16,17,22,23,35) but provides a more comprehensive molecular and electronic interpretation. The interpretation of experiment by this method agrees well with the results from QM/MM simulations (24,25) that also led to deviations from semiclassical 2°mSSEs in the forward direction.…”

supporting

confidence: 72%

“…These data completed the set of 2°KIEs available for this enzyme and allowed us to develop an empirical model that is consistent with all the data. This model shed light on the nature of the phenomenon described in the past as H tunneling and 1°-2°coupled motion (12,(15)(16)(17)(18). The picture of the reaction emphasizes the dual importance of a short DAD as well as degenerate donor and acceptor wells at the TRS.…”

Section: Discussionmentioning

confidence: 80%

“…Concurrent with these experimental findings, several theoreticians developed a simplified empirical underpinning to the concept of tunneling and coupled motion and predicted that deviations from the semiclassical Swain-Schaad exponents (SSEs) (14) could serve as strong evidence for such behavior (15)(16)(17). Semiclassically, the SSE is…”

mentioning

confidence: 99%

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Elusive transition state of alcohol dehydrogenase unveiled

Roston

Kohen

2010

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

154

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For several decades the hydride transfer catalyzed by alcohol dehydrogenase has been difficult to understand. Here we add to the large corpus of anomalous and paradoxical data collected for this reaction by measuring a normal (>1) 2°kinetic isotope effect (KIE) for the reduction of benzaldehyde. Because the relevant equilibrium effect is inverse (<1), this KIE eludes the traditional interpretation of 2°KIEs. It does, however, enable the development of a comprehensive model for the "tunneling ready state" (TRS) of the reaction that fits into the general scheme of Marcus-like models of hydrogen tunneling. The TRS is the ensemble of states along the intricate reorganization coordinate, where H tunneling between the donor and acceptor occurs (the crossing point in Marcus theory). It is comparable to the effective transition state implied by ensemble-averaged variational transition state theory. Properties of the TRS are approximated as an average of the individual properties of the donor and acceptor states. The model is consistent with experimental findings that previously appeared contradictory; specifically, it resolves the long-standing ambiguity regarding the location of the TRS (aldehyde-like vs. alcohol-like). The new picture of the TRS for this reaction identifies the principal components of the collective reaction coordinate and the average structure of the saddle point along that coordinate.hydrogen tunneling | enzyme kinetic | secondary isotope effect | Swain-Schaad E nzymes enhance the rates of chemical reactions by many orders of magnitude, and extensive studies have uncovered many aspects of how they do so. The prevailing theory that enzymes stabilize the transition state (TS) relative to the reactants explains many phenomena, and a great deal of contemporary research focuses on how enzymes stabilize the TS. An unfortunate hindrance to developing an understanding of how enzymes stabilize the TS lies in the enigmatic nature of the TS. Many enzymatic hydrogen (proton, hydrogen, or hydride) transfers, for example, occur by quantum mechanical tunneling, where a particle passes through an energy barrier because of its wave properties (1-6).Yeast alcohol dehydrogenase (yADH) serves as an excellent model system for enzyme-catalyzed H transfer because unlike many other enzymes, the chemical step, oxidation of a primary alcohol to an aldehyde by NAD þ , is rate-limiting with aromatic substrates (7). Furthermore, the thermodynamics of the reaction allow for examination of both the forward (alcohol to aldehyde) and reverse (aldehyde to alcohol) reactions under similar conditions (8). This type of nicotinamide-dependent redox reaction appears ubiquitously in biology, and a detailed picture of the TS of such reactions may facilitate many medical and industrial applications.Intriguingly, decades of experiments on the reaction catalyzed by yADH have returned what appear to be contradictory results, some suggesting an early TS, whereas others point to a late TS (7-10). In pioneering studies, Klinman measured linear fr...

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supporting

confidence: 72%

Section: Discussionmentioning

confidence: 80%

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Elusive transition state of alcohol dehydrogenase unveiled

Roston

Kohen

2010

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

154

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“…Such non-classical behaviour in the secondary position had, in fact, been predicted in the instance of coupling between the motions of the primary and secondary hydrogen atoms and tunnelling of the primary hydrogen from donor to acceptor atoms (Husky & Schowen 1983;Knapp et al in press). A very striking feature of the experimental data available from a large number of enzyme reactions is that the Swain-Schaad relationship for the primary isotope effect remains fairly close to the semi-classical limit when chemistry is rate determining (Knapp et al in press).…”

Section: Use Of the Swain-schaad Relationship As An Indicator Of Tunnmentioning

confidence: 93%

Linking protein structure and dynamics to catalysis: the role of hydrogen tunnelling

Klinman

2006

Phil. Trans. R. Soc. B

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Early studies of enzyme-catalysed hydride transfer reactions indicated kinetic anomalies that were initially interpreted in the context of a 'tunnelling correction'. An alternate model for tunnelling emerged following studies of the hydrogen atom transfer catalysed by the enzyme soybean lipoxygenase. This invokes full tunnelling of all isotopes of hydrogen, with reaction barriers reflecting the heavy atom, environmental reorganization terms. Using the latter approach, we offer an integration of the aggregate data implicating hydrogen tunnelling in enzymes (i.e. deviations from Swain-Schaad relationships and the semi-classical temperature dependence of the hydrogen isotope effect). The impact of site-specific mutations of enzymes plays a critical role in our understanding of the factors that control tunnelling in enzyme reactions.

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“…Empirical models of reaction coordinate transition have been constructed, but they require effects of quantum tunneling under the barrier as well as contribution from vibrational bond energy to explain the size of the observed effects. In particular, the secondary effect cannot be explained at all without invoking coupled dynamics of atoms [11]. All these additional contributions enhance the reaction rates beyond their values in the classical transition state theory, and hence would be favoured in useful biochemical processes by natural selection during evolution.…”

Section: Kinetic Isotope Effectmentioning

confidence: 99%

Wave Algorithms: Optimal Database Search and Catalysis

Patel¹

2006

AIP Conference Proceedings

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Abstract. Grover's database search algorithm, although discovered in the context of quantum computation, can be implemented using any physical system that allows superposition of states. A physical realization of this algorithm is described using coupled simple harmonic oscillators, which can be exactly solved in both classical and quantum domains. Classical wave algorithms are far more stable against decoherence compared to their quantum counterparts. In addition to providing convenient demonstration models, they may have a role in practical situations, such as catalysis. COMPUTING WITH WAVESAny physical system-with some initial state, some final state, and some interaction in between-is a candidate for processing information. One only needs to construct a suitable map between physical properties of the system and abstract mathematical variables. Most of the development in computer algorithms has been in the framework of "particle-like" discrete digital languages. It is known that "wave-like" analogue computation can also be carried out (e.g. using RLC circuits), but that has not been explored as intensively. The obvious reason is that discrete variables allow a degree of precision, by implementation of error correction procedures, that continuous variables cannot provide. In addition, computational complexity is believed to be the same for digital and analogue algorithms, so the choice between the two is left to considerations of hardware stability.With the advent of quantum computation, several quantum algorithms have been discovered, which are superior to their counterparts based on Boolean logic. Naturally, with both "particle-like" and "wave-like" behaviour at their disposal, quantum algorithms cannot do any worse than their classical counterparts. It is routinely stated that the simple parallelism provided by superposition and interference of quantum states is the key ingredient for the superiority of quantum algorithms. Now both superposition and interference are generic features of wave dynamics, and it is worthwhile to investigate the advantages they bring to an algorithm by exploring implementations based on "wave-like" behaviour alone. Of course, the classical wave implementations will be less efficient than the fully quantum ones, but they are expected to be much more stable (in particular, they have no entanglement and much weaker decoherence) and so may turn 1

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Reaction-coordinate tunneling in hydride-transfer reactions

Cited by 138 publications

References 0 publications

Elusive transition state of alcohol dehydrogenase unveiled

Elusive transition state of alcohol dehydrogenase unveiled

Linking protein structure and dynamics to catalysis: the role of hydrogen tunnelling

Wave Algorithms: Optimal Database Search and Catalysis

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