Semiquinone anion radicals of catechol(amine)s, catechol estrogens, and their metal ion complexes.

Kalyanaraman, Balaraman; Felix, Christopher C.; Sealy, Roger C.

doi:10.1289/ehp.8564185

Cited by 166 publications

(87 citation statements)

References 88 publications

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“…EPR Spectroscopy-The use of redox-inactive divalent metal cations, known to stabilize semiquinone radicals (28,29), allowed the spectra of a DOPAL semiquinone radical to be collected for the first time. Both two-electron (tyrosinase and NaIO 4 ) and one-electron oxidizing agents (HRP/H 2 O 2 and K 3 Fe(CN) 6 ) produced the same DOPAL semiquinone radical as seen by identical EPR spectra (Fig.…”

Section: Resultsmentioning

confidence: 99%

Oxidation of 3,4-Dihydroxyphenylacetaldehyde, a Toxic Dopaminergic Metabolite, to a Semiquinone Radical and an ortho-Quinone

Anderson

Mariappan

Buettner

et al. 2011

Journal of Biological Chemistry

122

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The oxidation and toxicity of dopamine is believed to contribute to the selective neurodegeneration associated with Parkinson disease. The formation of reactive radicals and quinones greatly contributes to dopaminergic toxicity through a variety of mechanisms. The physiological metabolism of dopamine to 3,4-dihydroxyphenylacetaldehyde (DOPAL) via monoamine oxidase significantly increases its toxicity. To more adequately explain this enhanced toxicity, we hypothesized that DOPAL is capable of forming radical and quinone species upon oxidation. Here, two unique oxidation products of DOPAL are identified. Several different oxidation methods gave rise to a transient DOPAL semiquinone radical, which was characterized by electron paramagnetic resonance spectroscopy. NMR identified the second oxidation product of DOPAL as the ortho-quinone. Also, carbonyl hydration of DOPAL in aqueous media was evident via NMR. Interestingly, the DOPAL quinone exists exclusively in the hydrated form. Furthermore, the enzymatic and chemical oxidation of DOPAL greatly enhance protein cross-linking, whereas auto-oxidation results in the production of superoxide. Also, DOPAL was shown to be susceptible to oxidation by cyclooxygenase-2 (COX-2). The involvement of this physiologically relevant enzyme in both oxidative stress and Parkinson disease underscores the potential importance of DOPAL in the pathogenesis of this condition. Parkinson disease (PD)2 involves specific loss of dopaminergic nuclei in the substantia nigra of the brain (1). Although the exact causes of this selective degeneration are unknown (2), the role of affected cells as centers of dopamine (DA) synthesis, storage, and metabolism suggests that DA may be an endogenous neurotoxin (3, 4) that contributes to the pathogenesis of PD. DA may act as a source of cellular oxidative stress and is known to undergo oxidation (Scheme 1) to cytotoxic radicals and quinones (5-8). Such oxidations can occur spontaneously or via metal-or enzyme-catalyzed mechanisms (9). One-electron oxidation of DA produces a radical capable of interfering with DA storage and causing oxidative protein and DNA modifications (5, 6, 10). Similarly, two-electron oxidation of DA to an ortho-quinone results in reactivity with cellular nucleophiles such as thiols and proteins (8, 11). Both species are capable of redox cycling, which could deplete cellular oxidative defenses. Also, in the presence of transition metals and/or O 2 , such oxidations could result in the production of ROS capable of inducing lipid peroxidation and damage to other cellular macromolecules (12). Another potential mechanism of toxicity for DA is its physiological metabolism to 3,4-dihydroxyphenylacetaldehyde (DOPAL) (13).DOPAL is a very reactive aldehyde that is 100 -1000-fold more toxic than DA both in vivo and in vitro (14,15). Physiological levels of DOPAL in the substantia nigra are ϳ2 M; levels as low as 6 M can exert significant toxicity (16). Reactivity with proteins, presumably via Schiff base formation, is an important mechanism o...

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Section: Resultsmentioning

confidence: 99%

Oxidation of 3,4-Dihydroxyphenylacetaldehyde, a Toxic Dopaminergic Metabolite, to a Semiquinone Radical and an ortho-Quinone

Anderson

Mariappan

Buettner

et al. 2011

Journal of Biological Chemistry

122

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“…2 A). Although intracellular GSH is necessary for Q detoxification by GST (2), it is also plausible that GSH protects as a result of reducing the SQ or the Q back to the catechol state (28).…”

Section: Discussionmentioning

confidence: 99%

“…The EPR spectrum obtained from such experiments (Fig. 3 Inset) can be attributed to the SQ radical of 4-OHE 2 (28). The half-life of the SQ radical stabilized by Zn 2ϩ was determined by following the EPR signal intensity of the free radical as a function of time after removal of excess H 2 O 2 by addition of catalase to the reaction mixture and was found to be Ͼ70 min (data not shown).…”

Section: Epr Studiesmentioning

confidence: 98%

“…Hydroxylated aromatic compounds such as the CEs are substrates of peroxidative enzymes such as HRP and produce the corresponding SQ radical (27). Inherently unstable SQ radicals of catecholamines can be detected by spin stabilization methods by using Zn 2ϩ in an acidic environment (28). Therefore, EPR experiments were performed in the presence of Zn 2ϩ to detect the estrogenic SQ radical.…”

Section: Epr Studiesmentioning

confidence: 99%

“…4 C and D). The putative mechanism of protection of these agents would be reduction of the SQ radical and Q back to the catecholic state in the case of cysteine (2) and the SQ to the catecholic state with ascorbate (28).…”

Section: Epr Studiesmentioning

confidence: 99%

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Semiquinone radical intermediate in catecholic estrogen-mediated cytotoxicity and mutagenesis: Chemoprevention strategies with antioxidants

Samuni

Chuang

Krishna

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Modulation of the cytotoxicity and mutagenicity of 4-hydroxyestradiol (4-OHE2), an oxidative metabolite of estrogen, by antioxidants was assessed in human MCF7 cells and TK-6 lymphoblast cells. The cytotoxicity of the catecholic estrogens was potentiated by depletion of intracellular glutathione and was independent of oxygen concentration. Agents such as the nitroxide Tempol can facilitate the oxidation of the semiquinone to the Q and enhanced 4-OHE2 cytotoxicity. Conversely, reducing agents such as ascorbate, cysteine, and 1,4-dihydroxytetramethylpiperidine (THP) protected against cytotoxicity and decreased mutation induction, presumably by reducing the semiquinone to the hydroquinone. Our results support the proposition that oxidation of the semiquinone to the corresponding Q is crucial in eliciting the deleterious effects of catecholic estrogens. Furthermore, because the deleterious effects of 4-OHE 2 were abrogated by dietary and synthetic antioxidants, our results would support the chemopreventive use of diets rich in reducing substances (vitamins and added synthetic antioxidants) as a means of decreasing the risks associated with estrogen exposure and developing of breast cancer.

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Charge‐Selectively Permeable Self‐Healing Microcapsules

Li,

Lutz‐Bueno,

Amstad

2023

Adv Materials Inter

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Microcapsules possessing a selective permeability are well‐suited vessels for conducting cell studies or chemical reactions that require selective exchanges of reagents over a prolonged time. Most currently reported microcapsules are single‐use delivery carriers since cargo is only released in significant amounts if their shells are damaged or the release relies on passive diffusion. Stable capsules possessing a selective, rapidly interchangeable permeability, which enables their repeated loading and unloading with selected reagents remain to be shown. Here, capsules are introduced that are composed of thin, viscoelastic, charge‐selective shells made of surfactants that are functionalized with a chelator, 3‐hydroxy‐4‐pyridinonone and crosslinked with appropriate nm‐sized ion clusters, for example composed of Fe3+/Tris or Al3+/Tris ion clusters. The charge selectivity of the shell permeability can be conveniently tuned with the crosslinking ion clusters. It is demonstrated that these capsules can be repeatedly loaded and unloaded with well‐defined substances. This feature enables their application as re‐usable selectively permeable filters to remove certain pollutants from solutions. These capsules are envisaged to be well‐suited for waste water treatment and as picoliter‐sized reaction vessels to selectively conduct chemical reactions within capsule cores while continuously supplying new reagents.

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Semiquinone anion radicals of catechol(amine)s, catechol estrogens, and their metal ion complexes.

Cited by 166 publications

References 88 publications

Oxidation of 3,4-Dihydroxyphenylacetaldehyde, a Toxic Dopaminergic Metabolite, to a Semiquinone Radical and an ortho-Quinone

Oxidation of 3,4-Dihydroxyphenylacetaldehyde, a Toxic Dopaminergic Metabolite, to a Semiquinone Radical and an ortho-Quinone

Semiquinone radical intermediate in catecholic estrogen-mediated cytotoxicity and mutagenesis: Chemoprevention strategies with antioxidants

Charge‐Selectively Permeable Self‐Healing Microcapsules

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