10.1021/jo025856w.s001
Waldemar Adam
Waldemar
Adam
Jens Hartung
Jens
Hartung
Hideki Okamoto
Hideki
Okamoto
Stefan Marquardt
Stefan
Marquardt
Werner M. Nau
Werner M.
Nau
Uwe Pischel
Uwe
Pischel
Chantu R. Saha-Möller
Chantu R.
Saha-Möller
Kristina Špehar
Kristina
Špehar
Photochemistry of <i>N</i>-Isopropoxy-Substituted 2(1<i>H</i>)-Pyridone and
4-<i>p</i>-Tolylthiazole-2(3<i>H</i>)-thione: Alkoxyl-Radical Release
(Spin-Trapping, EPR, and Transient Spectroscopy) and Its
Significance in the Photooxidative Induction of DNA Strand
Breaks
American Chemical Society
2002
EPR
DMPO
2 b
isopropoxypyridone 2 b
pyridone 2 b
thiazolethione 3 b
pyridone 2 b photoinduces
supercoiled pBR 322 DNA
isopropoxyl radicals
thiazolethione 3 b display
intermediary thiyl radicals B
2002-07-19 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Photochemistry_of_i_N_i_-Isopropoxy-Substituted_2_1_i_H_i_-Pyridone_and_4-_i_p_i_-Tolylthiazole-2_3_i_H_i_-thione_Alkoxyl-Radical_Release_Spin-Trapping_EPR_and_Transient_Spectroscopy_and_Its_Significance_in_the_Photooxidative_Induction_of_DNA_Strand_Break/3695298
UVA-irradiation of the photo-Fenton reagents <i>N</i>-isopropoxypyridone <b>2b</b> and <i>N</i>-isopropoxythiazole-2(3<i>H</i>)-thione <b>3b</b> releases radicals which induce strand breaks. Transient spectroscopy establishes
N−O bond scission [Φ<sub>N</sub><sub>-</sub><sub>O</sub> = (75 ± 8)% for <b>2b</b> and (65 ± 7)% <b>3b</b>] as the dominating primary
photochemical process to afford the DNA-damaging radicals. Product studies and laser-flash
experiments reveal that the thiazolethione <b>3b</b> leads primarily to the disulfide <b>5</b>, from which through
C−S bond breakage, the bithiazyl <b>6</b>, the thiazole <b>7</b>, and the isothiocyanate <b>8</b> are derived. Upon
irradiation of pyridone <b>2b</b> (300 nm) in aqueous media, a mixture of isopropoxyl and 2-hydroxyprop-2-yl radicals is formed, as confirmed by trapping with 5,5-dimethyl-1-pyrroline <i>N</i>-oxide (DMPO)
and EPR spectroscopy. In contrast, the photolysis of the thiazolethione <b>3b</b> (350 nm) affords
exclusively the DMPO adducts of the isopropoxyl radicals. Control experiments disclose that the
thiazolethione-derived photoproduct disulfide <b>5</b>, or the intermediary thiyl radicals <b>B</b>, scavenge the
carbon-centered 2-hydroxyprop-2-yl radicals, which are generated from the isopropoxyl radicals
by hydrogen shift. With supercoiled pBR 322 DNA in a 60:40 mixture of H<sub>2</sub>O−MeCN, the pyridone
<b>2b</b> and the thiazolethione <b>3b</b> display moderate strand-break activity (17% open-circular DNA for
<b>2b</b> and 12% for <b>3b</b>). In pure water, however, the pyridone <b>2b</b> photoinduces substantially more
DNA cleavage (32% open-circular DNA), which is attributed to the peroxyl radicals generated from
the 2-hydroxyprop-2-yl radicals by oxygen trapping. The lower strand-break activity of the
thiazolethione <b>3b</b> derives presumably from isopropoxyl radicals, because only these are detected
in the photolysis of this photo-Fenton reagent.