Mechanism of Acid-Catalyzed Hydrolysis of Formamide from Cluster-Continuum Model Calculations: Concerted versus Stepwise Pathway

Wang, Binju; Cao, Zexing

doi:10.1021/jp106560s

Cited by 72 publications

(67 citation statements)

References 61 publications

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“…Computational details are described in the Supporting Information. With the above the cluster continuum computational strategy, the Gibbs free energy of hydration of a proton in the form of a H 9 O 4 + cluster [35] was predicted to be À262.4 kcal mol À1 , in good agreement with the experimental values of À262.4 [30] and À264.1 kcal mol À1 . [31] Since the concerted hydration of carbonyl groups was recognized by previous computational studies, various concerted-hydration pathways for the water addition to the carbonyl group of methyl formate as a representative example were investigated, and the predicted Gibbs free energies of activation (DG°) range from 33.2 to 37.4 kcal mol À1 (B3LYP/6-311 + G(2df,2p) calculations) as shown in Table S1 of the Supporting Information.…”

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Hydration of Carbonyl Groups: The Labile H₃O⁺ Ion as an Intermediate Modulated by the Surrounding Water Molecules

Wang

Cao

2011

Angew Chem Int Ed

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Water plays a quite important role in chemical and biological processes, such as acid-base reactions, [1,2] proton transfer in membrane proteins, [3][4][5] keto-enol tautomerization, [6] and the hydration of carbonyl compounds. The hydration of carbonyl compounds has a long standing interest, both experimentally [7][8][9][10] and theoretically. [11][12][13][14][15][16][17][18][19][20][21][22] In most reactions of carbonyl compounds, such as aldehydes, ketones, esters, amides, the carboxylic acids, and their derivatives, the initial hydration or the nucleophilic addition of water at the carbonyl group, leading to a tetrahedral intermediate, is the rate-determining step. For example, the neutral hydrolyses of carboxylic acid derivatives normally proceed through the addition-elimination mechanism, [9] in which the hydration of the carbonyl group to yield a tetrahedral intermediate is the key step for hydrolysis.For the hydration of carbonyl compounds, all the previous ab-initio calculations proposed a concerted mechanism for the rate-determining hydration step, [11][12][13][14][15][16][17][18][19][20] including the nucleophilic attack of one water molecule onto the carbonyl carbon atom coupled with the concerted proton transfer to the carbonyl oxygen atom assisted by one or more water molecules as shown in Scheme 1. However, most of the calculated Gibbs free energies of activation (DG°) for the concerted mechanism exceed the experimental value considerably, [23] although calculations with a relatively small basis set happen to predict activation energies comparable to the experimental value. This unexpected agreement between theory and experiment can be ascribed to use of relatively small basis set (see below). In a recent study the initial water autoionization was assumed to be involved in the hydrolysis of esters, [23] and the predicted Gibbs activation energies by molecular dynamics (MD) simulations for the key steps are comparable to DG°of 23.8 kcal mol À1 for the water autoionization, [24] in agreement with the experimental value of 26.1 kcal mol À1 .[25] However, in this mechanism the water autoionization as the rate-determining step is a prerequisite to hydrolysis, implying that the Gibbs free energies of activation (DG°) are little changed for different esters.Nevertheless, the experimental rate constants for the hydration of esters can vary by 10 7 fold, which approximately corresponds to an activation energy difference of 10 kcal mol À1 . Experimental studies by Bell et al. suggested that the hydration of the carbonyl group may proceed through a stepwise transfer of three protons in a cyclic array of three water molecules, [26] and that an intermediate Eigen ion (H 3 O + ) [27] is most likely involved in hydration. However, to date, there is no computational evidence for H 3 O + as the key intermediate. This situation may arise from the use of inappropriate cluster models for hydrated species in previous computational studies. Theoretical calculations on the Gibbs free energy of hydration for the proton sh...

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Hydration of Carbonyl Groups: The Labile H₃O⁺ Ion as an Intermediate Modulated by the Surrounding Water Molecules

Wang

Cao

2011

Angew Chem Int Ed

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“…[82] More importantly, most of the transition states, reactants, and intermediates cannot be located only by the gasphase cluster model in calculation, as many charged species, especially for protons or hydronium ions, cannot be stabilized in the gas phase because of the loss of the bulk solvent effect. The direct calculation of the Gibbs energy in solution was also used in recent calculations, [22,[83][84][85][86][87][88] and was shown to be a practical approach. In calibration of the methodologies, we note that DFT calculations with the large basis set of 6-311 [22,89] whereas the relatively small 6-31G(d) basis set gave a remarkable underestimation of the reaction barrier of about 8 kcal mol…”

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confidence: 99%

“…[22,72,73] On the basis of extensive calculations, the relative reactivities of hydration and hydrolysis of the twisted amides and the substitution effect on the reactivity are discussed.…”

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“…(1)] and the corresponding Gibbs reaction energy in aqueous solution DG aq , the pK a value of the twisted amides could be calculated using Equation (2). [78] Considering that the first hydration shell of a proton contains at least four water molecules in a reliable theoretical treatment for its hydration Gibbs energy, [22,72,73] the proton-transfer reaction shown in Equation (1) can be equivalently represented by Equation (3). The calculated thermodynamic data and predicted pK a values are compiled in Table 1.…”

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Acid‐Catalyzed Reactions of Twisted Amides in Water Solution: Competition between Hydration and Hydrolysis

Wang¹,

Cao²

2011

Chemistry A European J

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The acid-catalyzed reactions of twisted amides in water solution were investigated by using cluster-continuum model calculations. In contrast to the previous widely suggested concerted hydration of the C=O group, our calculations show that the reaction proceeds in a practically stepwise manner, and that the hydration and hydrolysis channels of the C-N bond compete. The Eigen ion (H(3)O(+)) is the key species involved in the reaction, and it modulates the hydration and hydrolysis reaction pathways. The phenyl substitution in the twisted amide not only activates the N-CO bond, but also stabilizes the hydrolysis product through n(N)→π(phenyl) delocalization, leading exclusively to the hydrolysis product of the ring-opened carboxylic acid. Generally, the twisted amides are more active than the planar amides, and such a rate acceleration results mainly from the increase in exothermicity in the first N-protonation step; the second step of the nucleophilic attack is less affected by the twisting of the amide bond. The present results show good agreement with the available experimental observations.

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“…A similar work studied the acid-catalyzed hydrolysis of peptide bonds in model compounds via an amino-gem-diol intermediate pathway [17]. An acid-assisted hydrolysis of formamide with O-and Nprototonated pathways has also been studied by means of quantum mechanical methods [18].…”

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confidence: 99%

A density functional theory study on peptide bond cleavage at aspartic residues: direct vs cyclic intermediate hydrolysis

2013

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In this work, peptide bond cleavages at carboxy- and amino-sides of the aspartic residue in a peptide model via direct (concerted and step-wise) and cyclic intermediate hydrolysis reaction pathways were explored computationally. The energetics, thermodynamic properties, rate constants, and equilibrium constants of all hydrolysis reactions, as well as their energy profiles were computed at the B3LYP/6-311++G(d,p) level of theory. The result indicated that peptide bond cleavage of the Asp residue occurred most preferentially via the cyclic intermediate hydrolysis pathway. In all reaction pathways, cleavage of the peptide bond at the amino-side occurred less preferentially than at the carboxy-side. The overall reaction rate constants of peptide bond cleavage of the Asp residue at the carboxy-side for the assisted system were, in increasing order: concerted < step-wise < cyclic intermediate.

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Mechanism of Acid-Catalyzed Hydrolysis of Formamide from Cluster-Continuum Model Calculations: Concerted versus Stepwise Pathway

Cited by 72 publications

References 61 publications

Hydration of Carbonyl Groups: The Labile H₃O⁺ Ion as an Intermediate Modulated by the Surrounding Water Molecules

Hydration of Carbonyl Groups: The Labile H₃O⁺ Ion as an Intermediate Modulated by the Surrounding Water Molecules

Acid‐Catalyzed Reactions of Twisted Amides in Water Solution: Competition between Hydration and Hydrolysis

A density functional theory study on peptide bond cleavage at aspartic residues: direct vs cyclic intermediate hydrolysis

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Mechanism of Acid-Catalyzed Hydrolysis of Formamide from Cluster-Continuum Model Calculations: Concerted versus Stepwise Pathway

Cited by 72 publications

References 61 publications

Hydration of Carbonyl Groups: The Labile H3O+ Ion as an Intermediate Modulated by the Surrounding Water Molecules

Hydration of Carbonyl Groups: The Labile H3O+ Ion as an Intermediate Modulated by the Surrounding Water Molecules

Acid‐Catalyzed Reactions of Twisted Amides in Water Solution: Competition between Hydration and Hydrolysis

A density functional theory study on peptide bond cleavage at aspartic residues: direct vs cyclic intermediate hydrolysis

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Hydration of Carbonyl Groups: The Labile H₃O⁺ Ion as an Intermediate Modulated by the Surrounding Water Molecules

Hydration of Carbonyl Groups: The Labile H₃O⁺ Ion as an Intermediate Modulated by the Surrounding Water Molecules