Intramolecular migration of tritium and deuterium during nonenzymic aromatic hydroxylation

Jerina, Donald M.; Daly, John W.; Landis, William R.; Witkop, Bernhard; Udenfriend, Sidney

doi:10.1021/ja00989a044

Cited by 59 publications

(27 citation statements)

References 2 publications

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“…The relative fraction of 2HPB increased with decreasing electronegativity of the halogen, suggesting that the iodo-substituent was not retained on the ring as easily as the bromo-or chloro-substituent. This is consistent with results from earlier studies on the pathways followed by cytochrome P450 in the presence of substituted benzenes (Jerina et al 1967;Daly et al 1972). This suggests that subsequent intramolecular rearrangement is influenced by the electronic properties of the aromatic substituent, regardless of whether the arene oxide intermediate is involved.…”

Section: Discussionsupporting

confidence: 92%

Transformation of ortho -substituted biphenyls by Methylosinus trichosporium OB3b: substituent effects on oxidation kinetics and product formation

Lindner

Adriaens

Semrau

2000

Archives of Microbiology

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The ability of Methylosinus trichosporium OB3b, expressing soluble methane monooxygenase, to oxidize a range of ortho-substituted biphenyls was examined to better understand how substituents affect both the rate and products of oxidation in comparison to biphenyl. Inhibition of oxidation was observed over the tested substrate range for both biphenyl and ortho-halogenated biphenyls (2-chloro-, 2-bromo-, and 2-iodobiphenyl). No inhibition was observed during the oxidation of 2-hydroxybiphenyl and 2-methylbiphenyl. Analysis of the products of oxidation showed that, depending on the substituent, ring hydroxylation, substituent oxidation, and elimination pathways could occur. The type and abundance of products formed along with the relatively high kinetic isotope effect observed for deuterated vs. nondeuterated biphenyl (k(h)/k(d) = 3.4+/-0.02) are consistent with mechanisms that include both hydrogen abstraction and NIH-shift pathways. Knowledge of these substituent-dependent reaction rates and mechanisms enhances our understanding of the methanotrophic aryl transformation potential and allows for better prediction of the formation of oxidized intermediates by methanotrophic bacteria.

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Section: Discussionsupporting

confidence: 92%

Transformation of ortho -substituted biphenyls by Methylosinus trichosporium OB3b: substituent effects on oxidation kinetics and product formation

Lindner

Adriaens

Semrau

2000

Archives of Microbiology

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“…By contrast, the work of the National Institutes of Health group under Daly was hindered by the aromatic epoxides being ephemeral in aqueous environments. During this period, Jerina identified and worked out the mechanism for the "NIH shift," the intramolecular migration of a hydrogen atom upon hydroxylation (Jerina et al, 1967(Jerina et al, , 1968. At the same time, he demonstrated conversion of arene oxides to a series of metabolites including premercapturic derivatives and dihydrodiols (Jerina et al, 1968).…”

Section: A History Of Epoxide Hydrolasesmentioning

confidence: 99%

The 2014 Bernard B. Brodie Award Lecture—Epoxide Hydrolases: Drug Metabolism to Therapeutics for Chronic Pain

Kodani¹,

Hammock²

2015

Drug Metab Dispos

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Dr. Bernard Brodie's legacy is built on fundamental discoveries in pharmacology and drug metabolism that were then translated to the clinic to improve patient care. Similarly, the development of a novel class of therapeutics termed the soluble epoxide hydrolase (sEH) inhibitors was originally spurred by fundamental research exploring the biochemistry and physiology of the sEH. Here, we present an overview of the history and current state of research on epoxide hydrolases, specifically focusing on sEHs. In doing so, we start with the translational project studying the metabolism of the insect juvenile hormone mimic R-20458 [(E)-6,7-epoxy-1-(4-ethylphenoxy)-3,7-dimethyl-2-octene], which led to the identification of the mammalian sEH. Further investigation of this enzyme and its substrates, including the epoxyeicosatrienoic acids, led to insight into mechanisms of inflammation, chronic and neuropathic pain, angiogenesis, and other physiologic processes. This basic knowledge in turn led to the development of potent inhibitors of the sEH that are promising therapeutics for pain, hypertension, chronic obstructive pulmonary disorder, arthritis, and other disorders.

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“…Another possibility is that the intermediate could be a free radical (Tomaszewski, Jerina and Daly, 1975;Jerina et al, 1967). Mitchell and his colleagues, using a range of model compounds, have produced both in vivo and in vitro evidence that the N-hydroxylamine derivative is the most likely intermediate Potter et al, 1973;Jollow et al, 1974).…”

Section: Metabolism Of Paracetamolmentioning

confidence: 99%

Paracetamol

Meredith

Goulding

1980

Postgraduate Medical Journal

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Intramolecular migration of tritium and deuterium during nonenzymic aromatic hydroxylation

Cited by 59 publications

References 2 publications

Transformation of ortho -substituted biphenyls by Methylosinus trichosporium OB3b: substituent effects on oxidation kinetics and product formation

Transformation of ortho -substituted biphenyls by Methylosinus trichosporium OB3b: substituent effects on oxidation kinetics and product formation

The 2014 Bernard B. Brodie Award Lecture—Epoxide Hydrolases: Drug Metabolism to Therapeutics for Chronic Pain

Paracetamol

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