Why Are Proton Transfers at Carbon Slow? Self-Exchange Reactions

and, Cyrille Costentin; Savéant, Jean‐Michel

doi:10.1021/ja046467h

Cited by 29 publications

(24 citation statements)

References 94 publications

(42 reference statements)

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“…As illustration, the reaction rates of nitroalkanes with hydroxide are more than 10 10 -fold slower than that predicted for a normal Eigen acid (67). For such slow carbon acids, the charge delocalization that provides resonance stabilization of the anion progresses more slowly than does proton transfer (68), and heavy-atom intramolecular reorganization is generally the rate-limiting process (69). Establishing a clear physical chemistry basis for interpreting protein hydrogen exchange provides a means to characterize both the structure and the population of the protein heavy-atom reorganization processes that facilitate solvent access for the structurally buried amides.…”

Section: Resultsmentioning

confidence: 99%

Peptide Conformer Acidity Analysis of Protein Flexibility Monitored by Hydrogen Exchange

2009

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The amide hydrogens that are exposed to solvent in the high-resolution X-ray structures of ubiquitin, FK506-binding protein, chymotrypsin inhibitor 2, and rubredoxin span a billion-fold range in hydroxide-catalyzed exchange rates which are predictable by continuum dielectric methods. To facilitate analysis of transiently accessible amides, the hydroxide-catalyzed rate constants for every backbone amide of ubiquitin were determined under near physiological conditions. With the previously reported NMR-restrained molecular dynamics ensembles of ubiquitin (PDB codes 2NR2 and 2K39) used as representations of the Boltzmann-weighted conformational distribution, nearly all of the exchange rates for the highly exposed amides were more accurately predicted than by use of the high-resolution X-ray structure. More strikingly, predictions for the amide hydrogens of the NMR relaxation-restrained ensemble that become exposed to solvent in more than one but less than half of the 144 protein conformations in this ensemble were almost as accurate. In marked contrast, the exchange rates for many of the analogous amides in the residual dipolar coupling-restrained ubiquitin ensemble are substantially overestimated, as was particularly evident for the Ile 44 to Lys 48 segment which constitutes the primary interaction site for the proteasome targeting enzymes involved in polyubiquitylation. For both ensembles, “excited state” conformers in this active site region having markedly elevated peptide acidities are represented at a population level that is 102 to 103 above what can exist in the Boltzmann distribution of protein conformations. These results indicate how a chemically consistent interpretation of amide hydrogen exchange can provide insight into both the population and the detailed structure of transient protein conformations.

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Section: Resultsmentioning

confidence: 99%

Peptide Conformer Acidity Analysis of Protein Flexibility Monitored by Hydrogen Exchange

2009

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“…If we assume a bimolecular collision factor Z CPET ¼ 2 Â 10 10 M À1 s À1 , a value of c as small as 5 Â 10 À3 falls in line with the slowness of carbon acid deprotonation as compared to oxygen and nitrogen acids. 19 Switching to the PTET pathway, the standard free energy of the PT step may be derived from calculations in ref. 1b as DG 0…”

Section: Introductionmentioning

confidence: 99%

Hydrogen and proton exchange at carbon. Imbalanced transition state and mechanism crossover

Costentin

Savéant

2020

Chem. Sci.

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“…Such physical situations have been termed "nonadiabatic" in the proton transfer literature. 68 The other interesting aspect of this geometry is the proximity of states immediately above the barrier which provides for a high probability of over-barrier reflection of the wave packet if the initial packet has finite overlap with these over-barrier states. It must be noted that most methodologies that study quantum dynamics in large systems 125,126 do not adequately reproduce all three effects.…”

Section: A Accuracy Of Quantum Propagationmentioning

confidence: 99%

“…40 In addition, similar systems have been recently studied to understand the quantum nuclear effects involved in the slow deprotonation step of weak acid-base chemistry. 68 These studies 68 have, however, used Marcus' theory 131 to obtain quantum corrections on the proton transfer process. Here we aim to demonstrate the power of the current approach in contributing significantly to such studies by treating the electronic effects accurately within hybrid DFT; in addition full quantum dynamical effects of the hopping proton are accurately treated within the wave packet formalism.…”

Section: Phenol-amine System: Scattering Amplitudes From the Wave mentioning

confidence: 99%

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Quantum wave packet ab initio molecular dynamics: An approach to study quantum dynamics in large systems

Iyengar

Jakowski

2005

The Journal of Chemical Physics

121

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A methodology to efficiently conduct simultaneous dynamics of electrons and nuclei is presented. The approach involves quantum wave packet dynamics using an accurate banded, sparse and Toeplitz representation for the discrete free propagator, in conjunction with ab initio molecular dynamics treatment of the electronic and classical nuclear degree of freedom. The latter may be achieved either by using atom-centered density-matrix propagation or by using Born-Oppenheimer dynamics. The two components of the methodology, namely, quantum dynamics and ab initio molecular dynamics, are harnessed together using a time-dependent self-consistent field-like coupling procedure. The quantum wave packet dynamics is made computationally robust by using adaptive grids to achieve optimized sampling. One notable feature of the approach is that important quantum dynamical effects including zero-point effects, tunneling, as well as over-barrier reflections are treated accurately. The electronic degrees of freedom are simultaneously handled at accurate levels of density functional theory, including hybrid or gradient corrected approximations. Benchmark calculations are provided for proton transfer systems and the dynamics results are compared with exact calculations to determine the accuracy of the approach.

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Why Are Proton Transfers at Carbon Slow? Self-Exchange Reactions

Cited by 29 publications

References 94 publications

Peptide Conformer Acidity Analysis of Protein Flexibility Monitored by Hydrogen Exchange

Peptide Conformer Acidity Analysis of Protein Flexibility Monitored by Hydrogen Exchange

Hydrogen and proton exchange at carbon. Imbalanced transition state and mechanism crossover

Quantum wave packet ab initio molecular dynamics: An approach to study quantum dynamics in large systems

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