Heavy-atom Reorganization Research Articles

Dynamic barriers and tunneling. New views of hydrogen transfer in enzyme reactions

Abstract Hydrogen-transfer processes are expected to show appreciable quantum mechanical behavior. Intensive investigations of enzymes under their physiological conditions show this to be true in practically every example investigated. Initially, tunneling was treated either as a tunneling correction [cf. Bell, The Tunnel Effect in Chemistry, Chapman & Hall, New York, (l980)], or as corner-cutting [Truhlar et al., J. Chem. Phys. 100, 12771 (l996)]. This worked well as long as the observed properties could be explained by “corrections” to transition-state theory. However, over the past several years, enzymatic behaviors have been observed that are so deviant as to lie outside of transition-state theory. This phenomenon is discussed in the context of the enzyme, soybean lipoxygenase. An environmentally coupled hydrogen-tunneling model is presented that derives from the treatments of Kuznetsov and Ullstrup [Can. J. Chem. 77, 689 (l999)], and includes heavy-atom reorganization (temperature-dependent and largely isotope-independent), together with heavy-atom gating (temperature- and isotope-dependent). This treatment can explain a wide range of behaviors and leads to a new view of the origin of kinetic isotope effects in hydrogen-transfer reactions. These properties link enzyme fluctuations to the hydrogen-transfer reaction coordinate, making a quantum view of H-transfer necessarily a dynamic view of catalysis.

The decomposition of methyl hemiacetals of benzaldehyde in aqueous solution: a study of the effect of aromatic substitution

The acid-base catalysed decomposition of hydrates and hemiacetals of carbonyl compounds are classical examples of reactions where (slow) proton transfer is coupled with heavy atom reorganization, i.e., C—O bond breaking and solvent reorganization. We have studied the influence of m- and p-substitution in the carbonyl electrophile on the kinetics of the acid and base catalysis of the decomposition of methyl hemiacetals of benzaldehyde. The experimental data are well described by three-dimensional More O'Ferrall - Jencks energy contour diagrams according to principles developed by Jencks (the BEMA HAPOTHLE). Thus, for acid catalysis, a Cordes cross-interaction coefficient pxy' = δρ/δpKa = 0.15 indicates the coupled nature of the rate-limiting step in a class e mechanism, similar to conclusions reached from systematic substitution in the nucleophile. Our more extensive set of data for base catalysis permits a more rigorous analysis according to the BEMA HAPOTHLE. The data are consistent with a class n mechanism as also suggested earlier on the basis of substitution in the nucleophile. A slight upward curvature observed in the Hammett plots for the various catalysts is described by the direct correlation parameter py = -δρ/δσ = -0.11. This second derivative demonstrates the concerted nature of the C—O bond cleavage and O-H formation in the transition state, which changes with changing substituent. A class n mechanism for base catalysis is also supported by the observation of a Cordes cross-interaction parameter pxy = -δρ/δpKa = -δβ/δσ = 0.03, which describes the experimentally observed decrease in Hammett ρ with increasing pKa of the catalyst. This change may be rationalized by the movement of a saddle point on a diagonal reaction coordinate in the energy contour diagram, as a resultant of shifts parallel and perpendicular to the coordinate, when the energy along one side of the diagram is changed. It is concluded that observed rate changes as a result of substitution in the electrophile are consistent with and present further confirmation of earlier suggested mechanisms of hemiacetal decomposition reactions.Key words: methyl hemiacetals of benzaldehydes, acid-base catalysed breakdown, Hammett plots, More O'Ferrall - Jencks diagrams.

Identity-reaction proton transfers from oxygen acids yielding localized vs. delocalized conjugate bases. An ab initio study

Identity-reaction proton transfers from a series of oxygen acids to the corresponding conjugate bases have been studied by ab initio methods at the MP2/6-31+G*//MP2/6-31+G* level. The acids are H3O+, CH3OH2+, CH2 = OH+, HC(O)OH2+, CH2 = CHOH2+, H2O, CH3OH, HOOH, HOCH2OH, FOH, FCH2OH, HC(O)OH, and CH2 = CHOH. Gas-phase acidities were calculated at the G2(MP2) level in order to have benchmark values for all acidities regardless of whether experimental values were available. Barriers to proton transfer relative to the separated reactants, ΔHTS, show a straight-line relation to acidity for all but two of the neutral acids and for all but one of the cationic acids. Two neutral acids, HOOH and FOH, show negative deviations that can be attributed to polarizability of the atoms attached to the proton donor oxygens. The cationic acid HC(O)OH2+ shows a large positive deviation, which probably arises from substantial heavy-atom reorganization from reactant to TS. Charges provide evidence of a lag in delocalization in the reaction of CH2 = CHOH2+, though it does not show an elevated ΔHTS.Key words: ab initio, oxygen acids, proton transfer, acidity.

The decomposition of methyl hemiacetals of benzaldehyde in aqueous solution: a study of the effect of aromatic substitution

The acid-base catalysed decomposition of hydrates and hemiacetals of carbonyl compounds are classical examples of reactions where (slow) proton transfer is coupled with heavy atom reorganization, i.e., C—O bond breaking and solvent reorganization. We have studied the influence of m- and p-substitution in the carbonyl electrophile on the kinetics of the acid and base catalysis of the decomposition of methyl hemiacetals of benzaldehyde. The experimental data are well described by three-dimensional More O'Ferrall - Jencks energy contour diagrams according to principles developed by Jencks (the BEMA HAPOTHLE). Thus, for acid catalysis, a Cordes cross-interaction coefficient pxy' = δρ/δpKa = 0.15 indicates the coupled nature of the rate-limiting step in a class e mechanism, similar to conclusions reached from systematic substitution in the nucleophile. Our more extensive set of data for base catalysis permits a more rigorous analysis according to the BEMA HAPOTHLE. The data are consistent with a class n mechanism as also suggested earlier on the basis of substitution in the nucleophile. A slight upward curvature observed in the Hammett plots for the various catalysts is described by the direct correlation parameter py = -δρ/δσ = -0.11. This second derivative demonstrates the concerted nature of the C—O bond cleavage and O-H formation in the transition state, which changes with changing substituent. A class n mechanism for base catalysis is also supported by the observation of a Cordes cross-interaction parameter pxy = -δρ/δpKa = -δβ/δσ = 0.03, which describes the experimentally observed decrease in Hammett ρ with increasing pKa of the catalyst. This change may be rationalized by the movement of a saddle point on a diagonal reaction coordinate in the energy contour diagram, as a resultant of shifts parallel and perpendicular to the coordinate, when the energy along one side of the diagram is changed. It is concluded that observed rate changes as a result of substitution in the electrophile are consistent with and present further confirmation of earlier suggested mechanisms of hemiacetal decomposition reactions.Key words: methyl hemiacetals of benzaldehydes, acid-base catalysed breakdown, Hammett plots, More O'Ferrall - Jencks diagrams.

AM1 study on the mechanism of hydrolysis of nitrourea and solvation effect upon hydrolysis

The semi-empirical AM1 method has been employed to calculate the dynamics of hydrolysis of nitrourea in neutral, acidic and alkaline solutions. The geometries have been fully optimized for reactant, activated and product complexes for the hydrolysis reactions. In neutral and acidic media, the activated complexes have a four-membered ring structure, and the reaction-coordinated eigenvectors show heavy-atom reorganization and proton transfer to be truly concerted in both cases. In alkaline medium, the hydrolysis also involves the activated complex. In order to determine the influence of solvent on the hydrolysis, the reaction between one water molecule and nitrourea in neutral solution catalyzed by another molecule of water was also calculated. The results showed that one water molecule reduces the AM1 reaction barrier by 31.5 kJ mol −1 by virtue of increased hydrogen bonding in the cyclic six-membered activated complex.

Simultaneous occurrence of solvent reorganization and heavy-atom reorganization in a transmethylation transition state

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSimultaneous occurrence of solvent reorganization and heavy-atom reorganization in a transmethylation transition stateOsborne S. L. Wong and Richard L. SchowenCite this: J. Am. Chem. Soc. 1983, 105, 7, 1951–1954Publication Date (Print):April 1, 1983Publication History Published online1 May 2002Published inissue 1 April 1983https://doi.org/10.1021/ja00345a047RIGHTS & PERMISSIONSArticle Views57Altmetric-Citations4LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (531 KB) Get e-Alerts Get e-Alerts

Proton transfer between electronegative atoms: rate-determining or not?

Several carbonyl group reactions which involve rate—deter— mining proton transfer between electronegative atoms, as evidenced by biphasic Bronsted plots and detailed kinetic analysis, also give kinetic hydrogen isotope effects which change rapidly with the pKa differ— ence between the proton donor and the protonated proton acceptor (ipK) and peak sharply at LpK=O. This indicates that the proton transfer component of the overall proton transfer process (encounter of react— ants, proton transfer, and separation of products) is at least partly rate—determining in these systems, but it is so only over a narrow region of ipK about tpK=O. Kinetic isotope effects on the basecatalyzed decomposition of nitramide as well as the shape of the Bronsted plots for this reaction and the deprotonation of the conjugate acid of 2, 7—dimethoxy—l, 8-bis(dimethylamino)naphthalene indicate that proton transfer involving nitrogen is intrinsically slower than that involving oxygen and is therefore (partly) ratedetermining over a wider, albeit still rather limited, range of LpK. INTRODUCTION It is a tenet of long standing in mechanistic chemistry that proton transfer between electronegative atoms such as oxygen and nitrogen is seldom if ever rate-determining in a reaction where such transfer and changes in bonding between heavy atoms must take place. This idea is stated especially clearly in a Solvation Rule laid down by Swain, Kuhn and Schowen (1), who said: A proton being transferred from one oxygen (or nitrogen) to another in a reaction which requires heavy atom reorganization lie in an entirely stable potential at the transition state and should not form reacting bonds nor give rise to primary isotope effects. The origin of this idea is obscure, but it was undoubtedly fostered by the fact that rates of proton transfer between electronegative atoms, i.e. [in the Eigen sense (2)] acid-base centers, were for a long time too fast to measure. When appropriate fast reaction techniques were invented and the rates of normal acid-base reactions were finally measured and found to be very fast indeed (2), the idea was reinforced. Heavy atom reorganization, however, can also be very fast. An early indication that it might be fast enough to compete with proton transfer between electronegative atoms came from studies of oxygen-18 exchange during the hydrolysis of carboxylic acid esters which suggested that proton transfer from solvent water to the negatively charged oxygen atom of the tetrahedral intermediate formed in this reaction (eq. 1) might in some cases be kinetically significant (3). This requires reversal of tetrahedral intermediate Q HO 0 HO OH 1 2 ' 2 ' RCO +ROH 1 RCOR —Tg' ROR — ROR 2 OH OH formation, which involves bonding changes between oxygen and carbon, to be either faster than or at least of the same velocity as proton transfer between two oxygen atoms. Firm evidence that breakdown of tetrahedral intermediates can be faster than subsequent protonation of these species was

Base-catalysed decomposition of nitramide: Brønsted relations and a second reaction pathway

A new spectroscopic technique for measuring the rate of nitramide decomposition revealed a second pathway for this reaction and allowed extension of the Bronsted relation for the first (traditional) pathway into more basic regions where the onset of relatively sharp curvature was detected; these results suggest a mechanism for the first reaction pathway in which proton transfer is not concerted with heavy atom reorganization.

ChemInform Abstract: PATHWAYS OF PROTON TRANSFER IN ACETAL HYDROLYSIS

The process of acetal hydrolysis is analyzed in terms of the competing steps of proton transfer and heavy atom reorganization. The results of this analysis are portrayed in a series of three-dimensional reaction coordinate diagrams. The observed pathway of hydrolysis (A-1, general acid catalyzed, or spontaneous) is shown to depend on the energy of the various possible intermediates in these reactions.

Pathways of proton transfer in acetal hydrolysis

AbstractThe process of acetal hydrolysis is analyzed in terms of the competing steps of proton transfer and heavy atom reorganization. The results of this analysis are portrayed in a series of three‐dimensional reaction coordinate diagrams. The observed pathway of hydrolysis (A‐1, general acid catalyzed, or spontaneous) is shown to depend on the energy of the various possible intermediates in these reactions.

Amide hydrolysis. VI. Diffusion-controlled proton transfer and heavy-atom reorganization in the general acid, specific base catalyzed hydrolysis of amides

Amide hydrolysis. VI. Diffusion-controlled proton transfer and heavy-atom reorganization in the general acid, specific base catalyzed hydrolysis of amides

Amide hydrolysis. IV. Proton transfer and heavy-atom reorganization in amide hydrolysis. Valence-isomeric transition states

Amide hydrolysis. IV. Proton transfer and heavy-atom reorganization in amide hydrolysis. Valence-isomeric transition states