Properties and Reactivity of the Adenosine Radical Generated by Radiation-Induced Oxidation in Aqueous Solution

Itô, Takeo; Kuno, Susumu; Uchida, Takane; Fujita, Shin-ichi; Nishimoto, Sei‐ichi

doi:10.1021/jp801976t

Cited by 17 publications

(26 citation statements)

References 45 publications

(72 reference statements)

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“…These data are consistent with previously reported spectra of dA • , which also feature a broad absorbance centered around 590 nm. 13,21 Since the alkoxyamine 7b is in equilibrium with the oxime ether ( 7b -im), we calculated the UV-vis spectra of both the expected aminyl radical dA • and that of its iminyl tautomer (dA • -im) (Figure 2B). The calculations, using a N9-methyladenine analogue of dA • ( 24 ) and dA •- im ( 24 -im), indicate that the iminyl radical is 13.0 kcal/mol higher in energy in the gas phase than the aminyl radical (Figure 3).…”

Section: Resultsmentioning

confidence: 99%

Aminyl Radical Generation via Tandem Norrish Type I Photocleavage, β-Fragmentation: Independent Generation and Reactivity of the 2′-Deoxyadenosin- N6-yl Radical

et al. 2017

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Formal hydrogen atom abstraction from the nitrogen-hydrogen bonds in purine nucleosides produces reactive intermediates that are important in nucleic acid oxidation. Herein we describe an approach for the independent generation of the purine radical resulting from hydrogen atom abstraction from the N6-amine of 2′-deoxyadenosine (dA•). The method involves sequential Norrish Type I photocleavage of a ketone (7b) and β-fragmentation of the initially formed alkyl radical (8b) to form dA• and acetone. The formation of dA• was followed by laser flash photolysis, which yields a transient with λmax ~ 340 nm and a broader weaker absorption centered at ~560 nm. This transient grows in at ≥ 2 × 105 s−1; however, computations and reactivity data suggest that β-fragmentation occurs much faster, implying the consumption of dA• as it is formed. Continuous photolysis of 7b in the presence of ferrous ion or thiophenol produces good yields of dA, whereas less reactive thiols afford lower yields presumably due to a polarity mismatch. This tandem photochemical, β-fragmentation method promises to be useful for site-specific production of dA• in nucleic acid oligomers and/or polymers and also for the production of aminyl radicals, in general.

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Section: Resultsmentioning

confidence: 99%

Aminyl Radical Generation via Tandem Norrish Type I Photocleavage, β-Fragmentation: Independent Generation and Reactivity of the 2′-Deoxyadenosin- N6-yl Radical

et al. 2017

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“… The efficiency of DMPO trapping of this radical may be due to the more sterically accessible exocyclic NH 2 -derived adduct and/or product stability (the exocyclic adduct has an intact aromatic ring). This trapped radical may assume significance in DNA as this redox–neutral radical may be relatively stable [52], leading to A(adenine)-mediated hole migration to adjacent bases[53]. It has been predicted by hole-trapping researchers that the adenine radical cation contributes to the hole-transfer (HT) process through A/T sequences and exists as a real chemical intermediate [54-58].…”

Section: Discussionmentioning

confidence: 99%

Site-specific radical formation in DNA induced by Cu(II)–H2O2 oxidizing system, using ESR, immuno-spin trapping, LC-MS, and MS/MS

Bhattacharjee

Deterding

Chatterjee

et al. 2011

Free Radical Biology and Medicine

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Oxidative stress-related damage to the DNA macromolecule produces a multitude of lesions that are implicated in mutagenesis, carcinogenesis, reproductive cell death and aging. Many of these lesions have been studied and characterized by various techniques. Of the techniques that are available, the comet assay, HPLC-EC, GC-MS, HPLC-MS and especially HPLC-MS/MS remain the most widely used and have provided invaluable information on these lesions. However, accurate measurement of DNA damage has been a matter of debate. In particular, there have been reports of artifactual oxidation leading to erroneously high damage estimates. Further, most of these techniques measure the end product of a sequence of events and thus provide only limited information on the initial radical mechanism. We report here a qualitative measurement of DNA damage induced by a Cu(II)-H2O2 oxidizing system using immuno spin-trapping (IST) with EPR, MS and MS/MS. The radical generated is trapped by DMPO immediately upon formation. The DMPO adduct formed is initially EPR active but subsequently is oxidized to the stable nitrone, which can then be detected by IST and further characterized by MS and MS/MS.

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“…This adduct undergoes proton or hydrogen transfer, followed by dehydration, to form an N6-dehydrogenated radical. N6 has also been shown elsewhere to be the most likely site of hydrogen abstraction by hydroxyl radical (38,39). However, the absence of detection of other DNA radicals is not proof of their absence.…”

Section: Discussionmentioning

confidence: 82%

Detection and imaging of the free radical DNA in cells--Site-specific radical formation induced by Fenton chemistry and its repair in cellular DNA as seen by electron spin resonance, immuno-spin trapping and confocal microscopy

Bhattacharjee¹,

Chatterjee²,

Jiang³

et al. 2012

Nucleic Acids Research

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Oxidative stress-related damage to the DNA macromolecule produces lesions that are implicated in various diseases. To understand damage to DNA, it is important to study the free radical reactions causing the damage. Measurement of DNA damage has been a matter of debate as most of the available methods measure the end product of a sequence of events and provide limited information on the initial free radical formation. We report a measurement of free radical damage in DNA induced by a Cu(II)-H2O2 oxidizing system using immuno-spin trapping supplemented with electron paramagnetic resonance. In this investigation, the short-lived radical generated is trapped by the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) immediately upon formation. The DMPO adduct formed is initially electron paramagnetic resonance active, but is subsequently oxidized to the stable nitrone adduct, which can be detected and visualized by immuno-spin trapping and has the potential to be further characterized by other analytical techniques. The radical was found to be located on the 2′-deoxyadenosine (dAdo) moiety of DNA. The nitrone adduct was repaired on a time scale consistent with DNA repair. In vivo experiments for the purpose of detecting DMPO–DNA nitrone adducts should be conducted over a range of time in order to avoid missing adducts due to the repair processes.

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Properties and Reactivity of the Adenosine Radical Generated by Radiation-Induced Oxidation in Aqueous Solution

Cited by 17 publications

References 45 publications

Aminyl Radical Generation via Tandem Norrish Type I Photocleavage, β-Fragmentation: Independent Generation and Reactivity of the 2′-Deoxyadenosin- N6-yl Radical

Aminyl Radical Generation via Tandem Norrish Type I Photocleavage, β-Fragmentation: Independent Generation and Reactivity of the 2′-Deoxyadenosin- N6-yl Radical

Site-specific radical formation in DNA induced by Cu(II)–H2O2 oxidizing system, using ESR, immuno-spin trapping, LC-MS, and MS/MS

Detection and imaging of the free radical DNA in cells--Site-specific radical formation induced by Fenton chemistry and its repair in cellular DNA as seen by electron spin resonance, immuno-spin trapping and confocal microscopy

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