Hydroxyoxiranone: an ab initio MO investigation of the structure and stability of a model for a possible α-lactone intermediate in hydrolysis of sialyl glycosides

Firth-Clark, Stuart; Rodriquez, Christopher F.; Williams, Ian H.

doi:10.1039/a702817b

Cited by 7 publications

(4 citation statements)

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“…The lactone isomer of pyruvic acid was proposed in a theoretical study by Norris et al and was also considered by Kakkar et al, although no prior works appear to have examined the barrier for isomerization back to the acid form. The ability for hydroxy-α-lactones to readily isomerize with their more-stable carboxylic acid forms is of interest, however, as these compounds have been suggested as possible intermediates in the enzymatic hydrolysis of keto acids. , …”

Section: Resultsmentioning

confidence: 99%

“…The ability for hydroxyα-lactones to readily isomerize with their more-stable carboxylic acid forms is of interest, however, as these compounds have been suggested as possible intermediates in the enzymatic hydrolysis of keto acids. 45,46 The α-lactone 2 can decarboxylate to CH 3 COH, although this requires a very large barrier of 99 kcal mol −1 (not shown). Instead, CO elimination to produce acetic acid is much more favorable (TS2), with barrier height of 48.8 kcal mol −1 relative to pyruvic acid.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Decomposition of Pyruvic Acid on the Ground-State Potential Energy Surface

Silva

2015

J. Phys. Chem. A

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A potential energy surface is reported for isomerization and decomposition of gas-phase pyruvic acid (CH3C(O)C(O)OH) in its ground electronic state. Consistent with previous works, the lowest energy pathway for pyruvic acid decomposition is identified as decarboxylation to produce hydroxymethylcarbene (CH3COH), with overall barrier of 43 kcal mol(-1). This study discovers that pyruvic acid can also isomerize to the α-lactone form with a barrier of only 36 kcal mol(-1), from which CO elimination can occur at 49 kcal mol(-1) above pyruvic acid. An additional novel channel is identified for the tautomerisation of pyruvic acid to the enol form, via a double H-shift mechanism. The barrier for this process is 51 kcal mol(-1), which is around 20 kcal mol(-1) lower than the barrier for conventional keto-enol tautomerization via a 1,3-H shift transition state. Rate coefficients are calculated for pyruvic acid decomposition through RRKM theory/master equation simulations at 800-2000 K and 1 atm, showing good agreement with the available experimental data. The dissociation of vibrationally excited pyruvic acid produced through photoexcitation and subsequent internal conversion to the ground state is also modeled under tropospheric conditions and is seen to produce appreciable quantities of CO (∼1-4%) in addition to CH3COH via the dominant CO2 loss channel.

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Section: Resultsmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Decomposition of Pyruvic Acid on the Ground-State Potential Energy Surface

Silva

2015

J. Phys. Chem. A

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“…10 We also considered hydroxyoxiranone 8 as a model for a possible intermediate in the hydrolysis of glycosides of N-acetylα--neuraminic acid. 11 Our QCISD(t)=full/6-311++G(2df,p)// MP2=full/6-311++G(d,p) calculations led to an estimate of 104 kJ mol Ϫ1 for the conventional ring strain energy of 8, 65 kJ mol Ϫ1 less than that of 4. Furthermore, the ring-closed α-lactone structure 8 was predicted to be 21 kJ mol Ϫ1 lower in energy than the ring-opened zwitterion (cf.…”

Section: Introductionmentioning

confidence: 85%

Oxiranones: α-lactones or zwitterions? Insights from calculated electron density distribution analysis

Ruggiero

Williams

2001

J. Chem. Soc., Perkin Trans. 2

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Electron density distributions for oxiranone and hydroxyoxiranone have been analysed in vacuo p)] and in water [SCI-PCM/MP2/6-31+G(d,p)//HF/6-31+G(d,p)] and compared with those for cyclopropane, cyclopropanone, and oxirane. Oxiranone possesses a ring critical point in vacuo, and may be considered as an α-lactone with considerable ionic character in the endocyclic C α -O n bond. In water, oxiranone has neither a ring critical point nor a bond critical point for C α -O n , and may be considered as a zwitterion, whose carboxylate group has a net charge of Ϫ0.63. Geometrically, however, the molecule still possesses an acute-angled three-membered ring with a C α CO n angle of only 69Њ. Electronically, hydroxyoxiranone is acyclic and zwitterionic even in vacuo, but geometrically it still looks like an α-lactone.

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“…The retention stereochemistry could be a sign of a double displacement mechanism with a covalent intermediate (29). Note that with glycosides of N-acetylneuraminic acid, the term "covalent intermediate" as it applies to reaction stereochemistry includes an intermolecular covalent intermediate between enzyme and substrate, and an intramolecular covalent intermediate in which the substrate carboxylate group has formed an R-lactone by bond formation at the anomeric carbon (30,31). At the other extreme, the mechanism could involve a short-lived oxocarbenium ion intermediate having one face shielded by the enzyme to produce products with retention stereochemistry.…”

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confidence: 99%

Primary¹³C and β-Secondary²H KIEs for Trans-sialidase. A Snapshot of Nucleophilic Participation during Catalysis

Yang

Schenkman²,

Horenstein³

2000

Biochemistry

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Trypanosoma cruzi trans-sialidase catalyzes a novel reaction that involves the transfer of sialic acid between host and parasite glycoconjugates. In this paper, we report kinetic isotope effect studies on recombinant trans-sialidase. beta-Dideuterium and primary 13C isotope effects were measured for a good substrate, sialyl-lactose, and a slow substrate, sialyl-galactose, in both acid-catalyzed solvolysis and enzymatic transfer reactions. The beta-dideuterium isotope effect for sialyl-lactose in the acid hydrolysis reaction was 1.113 +/- 0.012. The primary 13C isotope effects for hydrolysis of sialyl-lactose and sialyl-galactose were 1. 016 +/- 0.011 and 1.015 +/- 0.008, respectively. In the enzymatic transfer reactions, the beta-dideuterium and primary 13C effects for sialyl-galactose were 1.060 +/- 0.008 and 1.032 +/- 0.008, respectively. The isotope effects for hydrolysis describe a dissociative SN1-like mechanism, and these data are contrasted by the data for the enzyme-catalyzed reaction. The enzymatic deuterium isotope effects are lower by a factor of 2, but the primary carbon isotope effects are higher by a factor of 2. This pattern describes a mechanism involving nucleophilic participation in the rate-determining transition state.

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Hydroxyoxiranone: an ab initio MO investigation of the structure and stability of a model for a possible α-lactone intermediate in hydrolysis of sialyl glycosides

Cited by 7 publications

References 15 publications

Decomposition of Pyruvic Acid on the Ground-State Potential Energy Surface

Decomposition of Pyruvic Acid on the Ground-State Potential Energy Surface

Oxiranones: α-lactones or zwitterions? Insights from calculated electron density distribution analysis

Primary¹³C and β-Secondary²H KIEs for Trans-sialidase. A Snapshot of Nucleophilic Participation during Catalysis

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Hydroxyoxiranone: an ab initio MO investigation of the structure and stability of a model for a possible α-lactone intermediate in hydrolysis of sialyl glycosides

Cited by 7 publications

References 15 publications

Decomposition of Pyruvic Acid on the Ground-State Potential Energy Surface

Decomposition of Pyruvic Acid on the Ground-State Potential Energy Surface

Oxiranones: α-lactones or zwitterions? Insights from calculated electron density distribution analysis

Primary13C and β-Secondary2H KIEs for Trans-sialidase. A Snapshot of Nucleophilic Participation during Catalysis

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Primary¹³C and β-Secondary²H KIEs for Trans-sialidase. A Snapshot of Nucleophilic Participation during Catalysis