Abstract：
:Although many phenols and catechols found as polyphenol natural products are antioxidants and have putative disease-preventive properties, others have deleterious health effects. One possible route to toxicity is the bioactivation of the phenolic function to quinones that are electrophilic, redox-agents capable of modifying DNA and proteins. The structure-property relationships of biologically important quinones and their precursors may help understand the balance between their health benefits and risks. We describe a mass-spectrometry-based study of four quinones produced by oxidizing flavanones and flavones. Those with a C2-C3 double bond on ring C of the flavonoid stabilize by delocalization of an incipient positive charge from protonation and render the protonated quinone particularly susceptible to nucleophilic attack. We hypothesize that the absence of this double bond is one specific structural determinant that is responsible for the ability of quinones to modify biological macromolecules. Those quinones containing a C2-C3 single bond have relatively higher aqueous stability and longer half-lives than those with a double bond at the same position; the latter have short half-lives at or below ∼1 s. Quinones with a C2-C3 double bond show little ability to depurinate DNA because they are rapidly hydrated to unreactive species. Molecular-orbital calculations support that quinone hydration by a highly structure-dependent mechanism accounts for their chemical properties. The evidence taken together support a hypothesis that those flavonoids and related natural products that undergo oxidation to quinones and are then rapidly hydrated are unlikely to damage important biological macromolecules.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Tu T,Giblin D,Gross MLdoi
10.1021/tx200140ssubject
Has Abstractpub_date
2011-09-19 00:00:00pages
1527-39issue
9eissn
0893-228Xissn
1520-5010journal_volume
24pub_type
杂志文章abstract：:Nitrofluorenes are mutagenic and carcinogenic environmental pollutants arising chiefly from combustion of fossil fuels. Nitro aromatic compounds undergo nitroreduction to N-hydroxy arylamines that bind to DNA directly or after O-esterification. This study analyzes the DNA binding and adducts from the in vitro nitrored...
journal_title：Chemical research in toxicology
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journal_title：Chemical research in toxicology
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journal_title：Chemical research in toxicology
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journal_title：Chemical research in toxicology
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
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journal_title：Chemical research in toxicology
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更新日期：1995-07-01 00:00:00
