Chain-breaking phenolic antioxidants: steric and electronic effects in polyalkylchromanols, tocopherol analogs, hydroquinones, and superior antioxidants of the polyalkylbenzochromanol and naphthofuran class

Barclay, L. R. C.; Vinqvist, Melinda R.; Mukai, Kazuo; Itoh, Shintaro; Morimoto, H.

doi:10.1021/jo00078a020

Cited by 97 publications

(77 citation statements)

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“…Unfortunately, 6 reacts directly with dioxygen, its solutions turning dark green on standing in air, yielding at least four products (TLC analysis). This "wasting" reaction with oxygen and possibly chain transfer reactions 6 are undoubtedly responsible for the unusually low stoichiometric factor found for 6 (viz. n ) 1.1).…”

Section: Aro-h + Dopphmentioning

confidence: 99%

Naphthalene Diols: A New Class of Antioxidants Intramolecular Hydrogen Bonding in Catechols, Naphthalene Diols, and Their Aryloxyl Radicals

et al. 2002

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Vous avez des questions? Nous pouvons vous aider. Pour communiquer directement avec un auteur, consultez la première page de la revue dans laquelle son article a été publié afin de trouver ses coordonnées. Si vous n'arrivez pas à les repérer, communiquez avec nous à PublicationsArchive-ArchivesPublications@nrc-cnrc.gc.ca. Questions? Contact the NRC Publications Archive team atPublicationsArchive-ArchivesPublications@nrc-cnrc.gc.ca. If you wish to email the authors directly, please see the first page of the publication for their contact information. NRC Publications Archive Archives des publications du CNRCThis publication could be one of several versions: author's original, accepted manuscript or the publisher's version. / La version de cette publication peut être l'une des suivantes : la version prépublication de l'auteur, la version acceptée du manuscrit ou la version de l'éditeur. NRC Publications Record / Notice d'Archives des publications de CNRC:http://nparc.cisti-icist.nrc-cnrc.gc.ca/eng/view/object/?id=489bf6ea-c7ae-4f4f-a366-b0ff338d365a http://nparc.cisti-icist.nrc-cnrc.gc.ca/fra/voir/objet/?id=489bf6ea-c7ae-4f4f-a366-b0ff338d365a 1,8-Naphthalenediol, 5, and its 4-methoxy derivative, 6, were found to be potent H-atom transfer (HAT) compounds on the basis of their rate constants for H-atom transfer to the 2,2-di(4-toctylphenyl)-1-picrylhydrazyl radical (DOPPH• , or as antioxidants during inhibited styrene autoxidation, k ArOH/ROO• , initiated with AIBN. The rate constants showed that 5 and 6 are more active HAT compounds than the ortho-diols, catechol, 1, 2,3-naphthalenediol, 2, and 3,5-ditert-butylcatechol, 3. Compound 6 has almost twice the antioxidant activity, k ArOH/ROO• ) 6.0 × 10, of that of the vitamin E model compound, 2,2,5,7,8-pentamethyl-6-chromanol, 4. Calculations of the O-H bond dissociation enthalpies compared to those of phenols, (∆BDEs), of 1-6 predict a HAT order of reactivity of 2 < 1 < 3 ≈ 4 < 5 < 6 in general agreement with kinetic results. Calculations on the diols show that intramolecular H-bonding stabilizes the radicals formed on H-atom transfer more than it does the parent diols, and this effect contributes to the increased HAT activity of 5 and 6 compared to the activities of the catechols. For example, the increased stabilization due to the intramolecular H-bond of 5 radical over 5 parent of 8.6 kcal/mol was about double that of 2 radical over 2 parent of 4.6 kcal/mol. Linear free energy plots of log k ArOH/DOPPH• and log k ArOH/ROO• versus ∆BDEs for compounds 1-6 along with available literature values for nonsterically hindered monophenols placed the compounds on common scales. The derived EvansPolanyi constants from the plots for the two reactions, R DOPPH • ) 0.48 >R ROO • ) 0.32, gave the expected order, since the ROO • reaction is more exothermic than the DOPPH • reaction. Compound 6 is sufficiently reactive to react directly with oxygen, and it lies off the log k ArOH/ROO• versus ∆BDE plot.

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Section: Aro-h + Dopphmentioning

confidence: 99%

Naphthalene Diols: A New Class of Antioxidants Intramolecular Hydrogen Bonding in Catechols, Naphthalene Diols, and Their Aryloxyl Radicals

et al. 2002

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“…This position makes hydroquinone highly active in terms of the biological properties. Besides that steric and 82,83 . With regard to the profiling assay against hCA II, hydroquinone was highly active, with K i value 706.79 nM.…”

Section: Resultsmentioning

confidence: 99%

“…In hydroquinone, two identical hydroxyl groups (-OH) are bonded to a benzene ring in an para-position. It was reported that para-position is favour of biological activity 12,82,83 . Many studies have demonstrated that the inhibition of CA II is due to the ability of an inhibitor to mimic the tetrahedral transition state when binding to the catalytic Zn 2+ located in the active site 78,84 .…”

Section: Resultsmentioning

confidence: 99%

The impact of hydroquinone on acetylcholine esterase and certain human carbonic anhydrase isoenzymes (hCA I, II, IX, and XII)

Scozzafava

Kalın

Supuran

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

102

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“…In guaiacol, a hydroxyl group (-OH) is bonded to a 1-methoxy benzene ring in an orthoposition. It was reported that para-position is favour of biological activity 30,74,75 . Many studies have demonstrated that the inhibition of CA II is due to the ability of an inhibitor to mimic the tetrahedral transition state when binding to the catalytic Zn 2+ located in the active site 1,4,19,71 .…”

Section: Resultsmentioning

confidence: 99%

“…It has been reported that phenolics are not biologically active unless substitution at either the ortho-or para-position has increased the electron density at the -OH group and lowered the oxygen-hydrogen bond energy. Steric and electronic effects are responsible for biological activity 30,74,75 . With regard to the profiling assay against hCA II, all the tested phenolic compounds (1-11) were active, with K i values in the range of 2.20-8.51 mM.…”

Section: Resultsmentioning

confidence: 99%

Carbonic anhydrase inhibitors: guaiacol and catechol derivatives effectively inhibit certain human carbonic anhydrase isoenzymes (hCA I, II, IX and XII)

Scozzafava

Passaponti

Supuran

et al. 2014

Journal of Enzyme Inhibition and Medicinal Chemistry

125

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Carbonic anhydrases (CAs) are widespread metalloenzymes in higher vertebrates including humans. A series of phenolic compounds, including guaiacol, 4-methylguaiacol, 4-propylguaiacol, eugenol, isoeugenol, vanillin, syringaldehyde, catechol, 3-methyl catechol, 4-methyl catechol and 3-methoxy catechol were investigated for their inhibition of all the catalytically active mammalian isozymes of the Zn 2+ -containing CA (EC 4.2.1.1). All the phenolic compounds effectively inhibited human carbonic anhydrase isoenzymes (hCA I, II, IX and XII), with K i s in the range of 2.20-515.98 lM. The various isozymes showed diverse inhibition profiles. Among the tested phenolic derivatives, compounds 4-methyl catechol and 3-methoxy catechol showed potent activity as inhibitors of the tumour-associated transmembrane isoforms (hCA IX and XII) in the submicromolar range, with high selectivity. The results obtained from this research may lead to the design of more effective carbonic anhydrase isoenzyme inhibitors (CAIs) based on such phenolic compound scaffolds.

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Chain-breaking phenolic antioxidants: steric and electronic effects in polyalkylchromanols, tocopherol analogs, hydroquinones, and superior antioxidants of the polyalkylbenzochromanol and naphthofuran class

Cited by 97 publications

References 1 publication

Naphthalene Diols: A New Class of Antioxidants Intramolecular Hydrogen Bonding in Catechols, Naphthalene Diols, and Their Aryloxyl Radicals

Naphthalene Diols: A New Class of Antioxidants Intramolecular Hydrogen Bonding in Catechols, Naphthalene Diols, and Their Aryloxyl Radicals

The impact of hydroquinone on acetylcholine esterase and certain human carbonic anhydrase isoenzymes (hCA I, II, IX, and XII)

Carbonic anhydrase inhibitors: guaiacol and catechol derivatives effectively inhibit certain human carbonic anhydrase isoenzymes (hCA I, II, IX and XII)

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