Unusual Double Beckmann Fragmentation Reaction under Physiological Conditions

The Journal of Organic Chemistry
Lin-Na XieBen-Zhan Zhu

Abstract

Pyridinium aldoximes, which are best-known as therapeutic antidotes for organophosphorus chemical warfare nerve-agents and pesticides, have been found to markedly detoxify polyhalogenated quinones, which are a class of carcinogenic intermediates and recently identified disinfection byproducts in drinking water. However, the exact chemical mechanism underlying this detoxication remains unclear. Here we demonstrate that pralidoxime can remarkably facilitate the dechlorination/hydroxylation of the highly toxic tetrachloro-1,4-benzoquinone in two-consecutive steps to generate the much less toxic 2,5-dichloro-3,6-dihydroxy-1,4-benzoquonine, with rate enhancements of up to 180 000-times. On the contrary, no accelerating effect was noticed with O-methylated pralidoxime. The major reaction product from pralidoxime was identified as its corresponding nitrile (2-cyano-1-methylpyridinium chloride). Along with oxygen-18 isotope-labeling studies, a reaction mechanism was proposed in which nucleophilic substitution coupled with an unprecedented double Beckmann fragmentation reaction was responsible for the dramatic enhancement in the detoxification process. This represents the first report of an unusually mild and facile Beckmann-type fragme...Continue Reading

References

Jul 1, 1990·Environmental Health Perspectives·T R Fukuto
Aug 1, 1973·Toxicology and Applied Pharmacology·I L Natoff, B Reiff
Mar 22, 2000·Chemical Research in Toxicology·J L BoltonT J Monks
Apr 16, 2002·Science·Bernard Meunier
Apr 16, 2002·Science·Sayam Sen GuptaTerrence J Collins
Aug 17, 2002·The Journal of Organic Chemistry·Lidia De LucaAndrea Porcheddu
Feb 12, 2005·Science·Emma L TeutenChristopher M Reddy
Jul 14, 2007·Science·Barry C KellyFrank A P C Gobas
Oct 31, 2007·Proceedings of the National Academy of Sciences of the United States of America·Ben-Zhan ZhuGui-Bin Jiang
Mar 18, 2008·Toxicology and Applied Pharmacology·C F ChignellM B Kadiiska
Jun 6, 2009·Proceedings of the National Academy of Sciences of the United States of America·Yang SongGarry R Buettner
Nov 16, 2010·Proceedings of the National Academy of Sciences of the United States of America·Ben-Zhan ZhuGuo-Qiang Shan
Mar 29, 2011·Journal of Medicinal Chemistry·Jarosław KalisiakJohn R Cashman
Nov 1, 1995·Environmental Science & Technology·D H SarrM D Aitken
Mar 1, 2012·Accounts of Chemical Research·Guillaume MerceyPierre-Yves Renard
Sep 19, 2012·Proceedings of the National Academy of Sciences of the United States of America·Ben-Zhan ZhuJun-Ge Zhu
Oct 11, 2013·Acta Crystallographica. Section E, Structure Reports Online·Michael N KammerJoel T Mague
Oct 12, 2013·Angewandte Chemie·Michael A DrahlLawrence J Williams
Oct 28, 2016·The Lancet Oncology·Kathryn Z GuytonUNKNOWN International Agency for Research on Cancer Monograph Working Group

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Ben-Zhan ZhuGuo-Qiang Shan
Sborník vědeckých prací Lékařské fakulty Karlovy univerzity v Hradci Králové. Supplementum
I Pohl
Analytical Chemistry
Edward T Urbansky, Matthew L Magnuson
© 2022 Meta ULC. All rights reserved