Gas-phase nucleophilic displacement reactions

Olmstead, William N.; Brauman, John I.

doi:10.1021/ja00455a002

Cited by 638 publications

(463 citation statements)

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“…[18][19][20][21][22] Having been so extensively studied, by both experimental [23][24][25][26][27] and computational [28][29][30][31][32][33][34][35][36] means, lends this class of reactions to be an outstanding starting position for benchmarking and refining new computational methods and techniques. In particular, the chloride/methyl chloride reaction is a strong candidate as a prototype reaction as it has been quite extensively studied in order to understand the exact nature of the transition state in the gas and condensed phases.…”

Section: Introductionmentioning

confidence: 99%

Quantum mechanical study of solvent effects in a prototype SN2 reaction in solution: Cl− attack on CH3Cl

Kuechler

York

2014

The Journal of Chemical Physics

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The nucleophilic attack of a chloride ion on methyl chloride is an important prototype S N 2 reaction in organic chemistry that is known to be sensitive to the effects of the surrounding solvent. Herein, we develop a highly accurate Specific Reaction Parameter (SRP) model based on the Austin Model 1 Hamiltonian for chlorine to study the effects of solvation into an aqueous environment on the reaction mechanism. To accomplish this task, we apply high-level quantum mechanical calculations to study the reaction in the gas phase and combined quantum mechanical/molecular mechanical simulations with TIP3P and TIP4P-ew water models and the resulting free energy profiles are compared with those determined from simulations using other fast semi-empirical quantum models. Both gas phase and solution results with the SRP model agree very well with experiment and provide insight into the specific role of solvent on the reaction coordinate. Overall, the newly parameterized SRP Hamiltonian is able to reproduce both the gas phase and solution phase barriers, suggesting it is an accurate and robust model for simulations in the aqueous phase at greatly reduced computational cost relative to comparably accurate ab initio and density functional models. © 2014 AIP Publishing LLC. [http://dx

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Section: Introductionmentioning

confidence: 99%

Quantum mechanical study of solvent effects in a prototype SN2 reaction in solution: Cl− attack on CH3Cl

Kuechler

York

2014

The Journal of Chemical Physics

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“…We use molecular dynamics computational simulation to examine model SN2 reactions roughly patterned after the CI + CH 3 CI reaction in water. The intrinsic SN 2 potential is taken to be the form of a double well, established in gas phase experiments 2 , 3 , 16 and quantum mechanical calculations,," 7 -20 but we take the methyl group as simplified to a single united atom. A fairly realistic model for flexible water is adopted.…”

Section: S'mentioning

confidence: 99%

Molecular dynamics of a model S N2 reaction in water

Bergsma

Gertner

Wilson

et al. 1987

The Journal of Chemical Physics

318

172

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Molecular dynamics are computed for a model SN2 reaction Cl−+CH3Cl→ClCH3+Cl− in water and are found to be strongly dependent on the instantaneous local configuration of the solvent at the transition state barrier. There are significant deviations from the simple picture of passage over a free energy barrier in the reaction coordinate, and thus, a marked departure from transition state theory occurs in the form of barrier recrossings. Factors controlling the dynamics are discussed, and, in particular, the rate of change of atomic charge distribution along the reaction coordinate is found to have a major effect on the dynamics. A simple frozen solvent theory involving nonadiabatic solvation is presented which can predict the outcome of a particular reaction trajectory by considering only the interaction with the solvent of the reaction system at the gas-phase transition barrier. The frozen solvent theory also gives the transmission coefficient κ needed to make the transition state theory rate agree with the outcome of the molecular dynamics trajectories. This theoretical κ value, which is the implementation for the SN2 reaction of the van der Zwan–Hynes nonadiabatic solvation transmission coefficient, is in good agreement with the trajectory results. In contrast, a Kramers theory description fails dramatically.

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“…1) (24)(25)(26)(27)(28)(29)(30). Part of the reason for the lack of a properly predicted barrier has to do with the size of the basis set of atomic orbitals (29) and another part, with the lack of solvation of the reactant in the computer experiments (5,49). Nevertheless, the process of turning the dipeptide into a conformation resembling a #l-lactam antibiotic is relatively facile, whereas the opposite process (50) of trying to flatten the bicyclic ring systems of the antibiotics so that they look more like a free dipeptide would certainly be much more difficult and less probable.…”

Section: Methodsmentioning

confidence: 99%

Transition state structures of a dipeptide related to the mode of action of beta-lactam antibiotics.

Boyd¹

1977

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

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The tetrahedral adducts formed during nucleophilic attack by a hydroxyl ion on the carbonyl carbon of a model dipeptide, glycylglycine, were studied by modifiedintermediate-neglect-of-differential-overlap molecular orbital calculations. This dipeptide is taken to represent the D-alanyl-D-alanine terminus of the polypeptides involved in the crosslinking transpeptidation reaction of peptidoglycan in bacterial cell walls. It Twelve years ago it was proposed (1) that the fl-lactam antibiotics derive their antibacterial activity because their structure mimics that of a transition state (TS) species formed when a D-alanyl-D-alanine peptide bond is cleaved at the receptor site of a proteolytic enzyme in bacterial cell walls. This idea has remained viable in the light of most subsequent research (e.g., see refs. 2-7 and references cited therein). The final step in cell wall synthesis, the crosslinking of the peptidoglycan strands via a transpeptidation reaction, is the one that is upset by penicillins and cephalosporins. Depending on the organism and the antibiotic, the inhibition can involve a transpeptidase or a carboxypeptidase, be reversible or irreversible, and lead either directly or indirectly to death of growing bacteria (2,4,(8)(9)(10)(11)(12)(13)(14)(15)(16). In bacteria that have been studied (2), the peptidoglycan crosslinks are polypeptides which in their precursor form have. a D-alanyl-D-alanine terminus. Little is known about the structural details of the TSs through which this dipeptide passes. Tipper and Strominger (1) and later Lee (3) noted that a twisting about the peptide C-N bond from the usual trans planar arrangement produces a structure that is more analogous to that of the fl-lactam antibiotics. Because of their bicyclic ring systems, the antibiotics have a CC-NC dihedral angle (corresponding to the CaC'-NCa dehedral angle in a polypeptide) in the range 132°-157°(17). Calculations (3, 5) on the amount of energy this twisting from 1800 requires have shown such structures to be accessible with the energy derivable from the usual sorts of substrate-receptor interactions.In principle, information about the TS structure could be deduced from the three-dimensional arrangement of the functionalities in the receptor site(s) of the relevant enzymes.The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 METHODThe approach was to use the computer as a reaction vessel in which to observe the reactants coming together and starting to react. Quantum mechanical computer calculations for "observing" TSs have the advantage of being able to stop the reaction at any point along the reaction path in order to observe at length species which, experimentally, would be very shortlived and not isolable. The "lens" for this "computer microscope" will be the modified-intermediate-neglect-of-differential-overlap (MINDO/3) molecular orbital (MO) method (22). This method has ...

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Gas-phase nucleophilic displacement reactions

Cited by 638 publications

References 11 publications

Quantum mechanical study of solvent effects in a prototype SN2 reaction in solution: Cl− attack on CH3Cl

Quantum mechanical study of solvent effects in a prototype SN2 reaction in solution: Cl− attack on CH3Cl

Molecular dynamics of a model S N2 reaction in water

Transition state structures of a dipeptide related to the mode of action of beta-lactam antibiotics.

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