Hydrolysis of formamide at 80.degree.C and pH 1-9

Hine, Jack; King, R. S.-M.; Midden, W. Robert; Sinha, A.

doi:10.1021/jo00329a007

Cited by 50 publications

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“…19 because they assumed that the rate constant for urea hydrolysis should be 2.8 times the rate constant for Me 4 U hydrolysis and because the rate constant for Me 4 U hydrolysis was 4.2×10 −12 s −1 . However, it has been known 47, 58 that the dominant pathway of amide hydrolysis is the alkaline hydrolysis (whose first-order rate constant is dependent on pH) and the first reaction step is rate-determining, whereas the dominant hydrolysis pathway for urea and Me 4 U is the neutral hydrolysis (whose first-order rate constant is independent of pH) as revealed by both the experimental observation 19 and our current computational data. The observed substituent shift of the rate constant for the alkaline hydrolysis of acetamide and N,N-dimethyl-acetamide is not necessarily applicable to that for the neutral hydrolysis of urea and Me 4 U.…”

Section: Resultssupporting

confidence: 56%

Reaction pathways and free energy profiles for spontaneous hydrolysis of urea and tetramethylurea: unexpected substituent effects

Yao

Chen

et al. 2013

Org. Biomol. Chem.

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It has been difficult to directly measure the spontaneous hydrolysis rate of urea and, thus, 1,1,3,3-tetramethylurea (Me4U) was used as a model to determine the “experimental” rate constant for urea hydrolysis. The use of Me4U was based on an assumption that the rate of urea hydrolysis should be 2.8 times that of Me4U hydrolysis because the rate of acetamide hydrolysis is 2.8 times that of N,N-dimethyl-acetamide hydrolysis. The present first-principles electronic-structure calculations on the competing non-enzymatic hydrolysis pathways have demonstrated that the dominant pathway is the neutral hydrolysis via the CN addition for both urea (when pH<~11.6) and Me4U (regardless of pH), unlike the non-enzymatic hydrolysis of amides where alkaline hydrolysis is dominant. Based on the computational data, the substituent shift of free energy barrier calculated for the neutral hydrolysis is remarkably different from that for the alkaline hydrolysis, and the rate constant for the urea hydrolysis should be ~1.3×109-fold lower than that (4.2×10−12 s−1) measured for the Me4U hydrolysis. As a result, the rate enhancement and catalytic proficiency of urease should be 1.2×1025 and 3×1027 M−1, respectively, suggesting that urease surpasses proteases and all other enzymes in its power to enhance the rate of reaction. All of the computational results are consistent with available experimental data for Me4U, suggesting that the computational prediction for urea is reliable.

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Section: Resultssupporting

confidence: 56%

Reaction pathways and free energy profiles for spontaneous hydrolysis of urea and tetramethylurea: unexpected substituent effects

Yao

Chen

et al. 2013

Org. Biomol. Chem.

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“…[6][7][8][9][10] In addition, amide bonds show a characteristic stability towards nucleophilic attack. [11,12] Energetic stability is also important because it confers the required degree of stability and rigidity to the amide/peptide linkage necessary to act as the protein scaffold. Not surprisingly, therefore, many theoretical studies have tried to explain these properties in terms of basic physicalchemical concepts.…”

Section: Introductionmentioning

confidence: 99%

Resonance Structures of the Amide Bond: The Advantages of Planarity

Mujika

Matxain

Eriksson

et al. 2006

Chemistry A European J

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Delocalization indexes based on magnitudes derived from electron-pair densities are demonstrated to be useful indicators of electron resonance in amides. These indexes, based on the integration of the two-electron density matrix over the atomic basins defined through the zero-flux condition, have been calculated for a series of amides at the B3LYP/6-31+G* level of theory. These quantities, which can be viewed as a measure of the sharing of electrons between atoms, behave in concordance with the traditional resonance model, even though they are integrated in Bader atomic basins. Thus, the use of these quantities overcomes contradictory results from analyses of atomic charges, yet keeps the theoretical appeal of using nonarbitrary atomic partitions and unambiguously defined functions such as densities and pair densities. Moreover, for a large data set consisting of 24 amides plus their corresponding rotational transition states, a linear relation was found between the rotational barrier for the amide and the delocalization index between the nitrogen and oxygen atoms, indicating that this parameter can be used as an ideal physical-chemical indicator of the electron resonance in amides.

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“…k w 4k H ½H þ þ k OH ½HO À at pH min . However, the observed kinetic data on hydrolysis of simple amides (such as formamide and acetamide) reveal that the values of k w are in the order of those of (k H ½H þ þ k OH ½HO À ) at pH min [87,98]. A plausible reaction mechanism for the reaction of H 2 O with imides is shown in Scheme 12 where k 1 -and k 4 -steps represent the alternative reaction paths for the formation of the highly aqueous reactive tetrahedral intermediate 12 T 0 .…”

Section: Mechanism Of the Nucleophilic Reaction Of Water With Imidementioning

confidence: 99%

Can a Typical Protein Assist the Rate of its Own Aqueous Cleavage?

Khan

2010

Progress in Reaction Kinetics and Mechanism

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Implications of k un and k H for the aqueous cleavage of proteins 153 9.2 Mechanistic aspects of aqueous un-, H þ -and HO À -catalysed cleavage of the imide bond 155 9.2.1 The mechanism of the nucleophilic reaction of water with imide 158 9.2.2 The mechanism of H þ -catalysed hydrolysis of imide bond 160 9.3 Aqueous pH -independent cleavage of amide bond of diamides (5, 15 -18) 160 10. CONCLUSIONS 161 11. ACKNOWLEDGEMENTS 161 12. REFERENCES 162 132 Mohammad Niyaz Khan www.prkm.co.uk ABSTRACTA recent finding of a large rate enhancement in the intramolecular secondary amide group-assisted cleavage of an adjacent tertiary amide bond predicts the possibility of the cleavage of the peptide bond of a protein through a similar reaction mechanism. Based upon enzymatic partial model reactions, the usual proton-switch mechanism has been suggested for the acylation step of the chymotrypsin -catalysed cleavage of the peptide bond which does not favour a His57-shift mechanism -an essential component of the classical charge relay mechanism. Also, the proton-switch mechanism does not necessarily require the two proton-transfer of the classical charge relay mechanism. The unique structural feature of the imidazole moiety of His57 is concluded to be essential in decreasing the rate of collapse of the proposed reactive tetrahedral intermediate back to the reactants. The proposed intramolecular intimate ion-pair formation between anionic Asp102 and cationic His57 is attributed to the energetically preferred location of the proton at Nd 1 of the imidazole moiety of His57. Thus, the analysis described in this review does not favour the necessary requirements of a two proton-transfer and His57-shift as proposed in the classical charge relay mechanism as well as the relatively recently proposed His57-flip mechanism.KEYWORDS: hydrolysis of amide and imide bond, intramolecular assistance, implication for peptide hydrolysis, enzyme-catalysed cleavage of peptide bond, proton-switch mechanism Prog React Kinet Mech 35: 131 -165.

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Hydrolysis of formamide at 80.degree.C and pH 1-9

Cited by 50 publications

References 0 publications

Reaction pathways and free energy profiles for spontaneous hydrolysis of urea and tetramethylurea: unexpected substituent effects

Reaction pathways and free energy profiles for spontaneous hydrolysis of urea and tetramethylurea: unexpected substituent effects

Resonance Structures of the Amide Bond: The Advantages of Planarity

Can a Typical Protein Assist the Rate of its Own Aqueous Cleavage?

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