Additivity Rules Using Similarity Models for Chemical Reactivity: Calculation and Interpretation of Electrofugality and Nucleofugality

Bentley, T. William

doi:10.1002/chem.200600517

Cited by 30 publications

(30 citation statements)

References 43 publications

(72 reference statements)

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“…Bentley has correctly criticized that some of the rate constants used for the calculation of E f , N f , and s f in our original work were incorrect because of common ion return [23]. However, recent work by Denegri and Kronja [24] confirmed the necessity to leave s f variable for the correlation analysis and not to employ only two parameters for describing the whole set of data as suggested by Bentley [23].…”

Section: Ionization Ratesmentioning

confidence: 74%

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How to predict changes in solvolysis mechanisms

Mayr

Ofial

2009

Pure and Applied Chemistry

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Stopped-flow and laser flash techniques have been employed to investigate the individual steps of the solvolysis reactions of benzhydryl (diarylmethyl) halides and carboxylates. In this way, absolute rate constants for the ionization (k 1 ), recombination of the carbocation with the leaving group (k -1 ), and subsequent reaction with the solvent (k SolvOH ) have been determined. As the stabilization of the carbocations increases, the mechanism changes from (a) S N 1 reactions with irreversible ionization through (b) S N 1 reactions with common-ion return and (c) S N 2C + reactions, where the intermediate carbocations accumulate, to (d) the formation of persistent carbocations which do not undergo subsequent reactions under the selected solvolysis conditions. The correlation equation log k = s(N + E), where the carbocations are characterized by the electrophilicity parameter E, and leaving groups and solvents are characterized by the nucleophile-specific parameters s and N can be employed to predict the changes of mechanism.

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Section: Ionization Ratesmentioning

confidence: 74%

“…However, recent work by Denegri and Kronja [24] confirmed the necessity to leave s f variable for the correlation analysis and not to employ only two parameters for describing the whole set of data as suggested by Bentley [23]. The reason for the choice of eq.…”

Section: Ionization Ratesmentioning

confidence: 82%

How to predict changes in solvolysis mechanisms

Mayr

Ofial

2009

Pure and Applied Chemistry

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“…It should also be mentioned that Bentley proposed the electrofugality parameters to be defined from the solvolysis rates of chlorides in 80% aqueous ethanol, and proposed a modified equation for calculating the reaction rate, assuming s f = 1 [37]. …”

Section: Introductionmentioning

confidence: 99%

Effect of the Leaving Group and Solvent Combination on the LFER Reaction Constants

Matić¹,

Jurić²,

Denegri³

et al. 2012

IJMS

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Fine effects that influence the variations of the reaction constants sf in LFER log k = sf(Nf + Ef) have been summarized here. Increasing solvent polarity in the series of binary mixtures increases the solvolysis rates for the same factor for all benzhydryl derivatives in which the solvation of the leaving group moiety in the transition state is substantial, i.e., log k vs. Ef correlation lines are parallel (same sf). For the substrates in which the demand for solvation of the leaving groups moiety is reduced, (e.g., carbonates) sf parameters decrease as the fraction of the water in a given solvent/water mixture increases (log k vs. Ef plots converge), due to decreasing solvation of the electrofuge moiety toward bigger electrofugality. The abscissa of the intersection of the converging plots might indicate the critical electrofugality above which the solvolysis rates should not depend of the water fraction. Larger reaction constant sf indicate later transition state for structurally related substrates only, while sf parameters for structurally different substrates cannot be compared likely due to different intrinsic barriers. Inversion in relative abilities of leaving groups is possible if they have similar reactivities and are characterized with different reaction constants.

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“…Lysis of glutathione disulfide (GSSG) with strong alkali produces EdAG as one of the identified products (Jones et al, 1983). The elimination reaction can be facilitated by the presence of a good leaving group in the β-position (Bentley, 2006). For example, EdAG can be readily synthesized from a dinitrophenyl derivative of GSH (Asquith and Carthew, 1972).…”

Section: Introductionmentioning

confidence: 99%

Dehydroalanine Analog of Glutathione: An Electrophilic Busulfan Metabolite That Binds to Human GlutathioneS-Transferase A1-1

Younis¹,

Elliott²,

Peer³

et al. 2008

J Pharmacol Exp Ther

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Elimination of hydrogen sulfide from glutathione (GSH) converts a well-known cellular nucleophile to an electrophilic species, γ-glutamyldehydroalanylglycine (EdAG). We have found that a sulfonium metabolite formed from GSH and busulfan undergoes a facile β-elimination reaction to give EdAG, which is an αβ-unsaturated dehydroalanyl analog of GSH. EdAG was identified as a metabolite of busulfan in a human liver cytosol fraction. EdAG condenses with GSH in a Michael addition reaction to produce a lanthionine thioether (GSG), which is a non-reducible analog of glutathione disulfide (GSSG). EdAG was less cytotoxic than busulfan to C6 rat glioma cells. GSH and EdAG were equally effective in displacing a glutathione S-transferase isozyme (human GSTA1-1) from a GSH-Agarose column. The finding of an electrophilic metabolite of GSH suggests that alteration of cellular GSH concentrations, irreversible non-reducible glutathionylation of proteins, and interference with GST function may contribute to the toxicity of busulfan.

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Additivity Rules Using Similarity Models for Chemical Reactivity: Calculation and Interpretation of Electrofugality and Nucleofugality

Cited by 30 publications

References 43 publications

How to predict changes in solvolysis mechanisms

How to predict changes in solvolysis mechanisms

Effect of the Leaving Group and Solvent Combination on the LFER Reaction Constants

Dehydroalanine Analog of Glutathione: An Electrophilic Busulfan Metabolite That Binds to Human GlutathioneS-Transferase A1-1

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