Computer Modeling of Phenyl Acetate Hydrolysis in Water and in Reaction with .beta.-Cyclodextrin: Molecular Orbital Calculations with the Semiempirical AM1 Method and the Langevin Dipole Solvent Model

Luzhkov, V. B.; Venanzi, Carol A.

doi:10.1021/j100008a012

Cited by 32 publications

(32 citation statements)

References 9 publications

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“…Only two studies have examined hydroxide addition to aryl esters, which are activated esters that are easier to hydrolyze than alkyl esters. Luzhov and Venanzi reported AM1 calculations for hydroxide addition to phenyl acetate in the gas phase and in solution 37. In a study on the fidelity of phosphonate haptens, Tantillo and Houk performed detailed analyses of the complete reaction pathways for hydroxide attack on phenyl acetate and on p ‐nitrophenyl acetate at the HF/6‐31+G*//HF/6‐31+G* and MP2/6‐31+G*//HF/6‐31+G* levels in the gas phase; incorporating solvation effects through PCM and SCI‐PCM calculations 38.…”

Section: Resultsmentioning

confidence: 99%

Direct hydroxide attack is a plausible mechanism for amidase antibody 43C9

et al. 2003

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Direct hydroxide attack on the scissile carbonyl of the substrate has been suggested as a likely mechanism for esterase antibodies elicited by phosphonate haptens, which mimic the transition states for the alkaline hydrolysis of esters.1 The unique amidase activity of esterase antibody 43C9 has been attributed to nucleophilic attack by an active-site histidine residue.2 Yet, the active site of 43C9 is strikingly similar to those of other esterase antibodies, particularly 17E8. We have carried out quantum mechanical calculations, molecular dynamics simulations, and free energy calculations to assess the mechanism involving direct hydroxide attack for 43C9. Results support this mechanism and suggest that the mechanism is plausible for other antiphosphonate antibodies that catalyze the hydrolysis of (p-nitro)phenyl esters.

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Section: Resultsmentioning

confidence: 99%

Direct hydroxide attack is a plausible mechanism for amidase antibody 43C9

et al. 2003

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“…The usual result is typically similar to what might be deduced from CPK molecular models together with conventional chemical concepts. Considerable variety in guest type has been studied. ,,,,,,− …”

Section: E Calculational Methodsmentioning

confidence: 99%

The Stability of Cyclodextrin Complexes in Solution

1997

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“…Some authors have tried to interpret the experimentally observed rate accelerations based on Molecular Mechanics 16, 20 and Molecular Dynamics calculations 18 for CD-ester complexes and the corresponding acetylated CD derivatives. The semiempirical AM1 method 21 and the empirical valence bond approach, 22 have also been used to investigate alkaline hydrolysis and have provided interesting interpretations based on solvation and binding energy changes. It is also interesting to note that Molecular Mechanics calculations have been done to investigate the interaction modes between a-, b-, or g-CD with several S-phenyl thiobenzoates, suggesting that the inclusion of the phenyl group bound to the carboxylate group is more favorable than that of the phenyl group attached to the sulfur atom.…”

Section: Introductionmentioning

confidence: 99%

Computer simulation of reactions in β-cyclodextrin molecular reactors: transition state recognition

et al. 2010

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Cyclodextrins have attracted much interest in recent years because of their potential use as molecular reactors allowing organic reactions in aqueous solution. To better understand their effect on reaction mechanisms, we have carried out a computational study of a prototypical process (neutral ester hydrolysis) in a beta-cyclodextrin (beta-CD). Two models have been used for the reactor. The first and simpler one assumes that the medium can be described by a polarizable dielectric continuum. The second one takes into account the discrete nature of the beta-CD and water molecules thanks to a computational approach that combines the use of Quantum Mechanics, Molecular Mechanics and Molecular Dynamics techniques. We focus on neutral pH processes for which either acceleration or inhibition has experimentally been observed depending on ester derivatives. Our calculations rationalize such observations by showing that the two reaction mechanisms usually invoked for hydrolysis, stepwise (involving two transitions states with formation of a -C(OH)(2)OR tetrahedral intermediate) and concerted, undergo opposite effects in the beta-CD environment. The results highlight the role played by molecular shape recognition. Thus, in spite of a higher polarity exhibited by the three transition states with respect to the reactants, the interactions with the beta-CD cavity may either increase or decrease the activation barrier due to different 3D-arrangements of the chemical structures.

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Computer Modeling of Phenyl Acetate Hydrolysis in Water and in Reaction with .beta.-Cyclodextrin: Molecular Orbital Calculations with the Semiempirical AM1 Method and the Langevin Dipole Solvent Model

Cited by 32 publications

References 9 publications

Direct hydroxide attack is a plausible mechanism for amidase antibody 43C9

Direct hydroxide attack is a plausible mechanism for amidase antibody 43C9

The Stability of Cyclodextrin Complexes in Solution

Computer simulation of reactions in β-cyclodextrin molecular reactors: transition state recognition

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