Photochemistry of N-Isopropoxy-Substituted 2(1H)-Pyridone and 4-p-Tolylthiazole-2(3H)-thione:  Alkoxyl-Radical Release (Spin-Trapping, EPR, and Transient Spectroscopy) and Its Significance in the Photooxidative Induction of DNA Strand Breaks

• Published in: Journal of organic chemistry Vol. 67; no. 17; pp. 6041 - 6049
• Main Authors: Adam, Waldemar, Hartung, Jens, Okamoto, Hideki, Marquardt, Stefan, Nau, Werner M, Pischel, Uwe, Saha-Möller, Chantu R, Špehar, Kristina
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 23.08.2002; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; DNA Damage; Electron Spin Resonance Spectroscopy; Exact sciences and technology; Free radicals chemistry; General and physical chemistry; Hydroxyl Radical - chemistry; In Vitro Techniques; Magnetic Resonance Spectroscopy; Molecular Structure; Organic chemistry; Oxidation-Reduction; Photochemistry; Photolysis; Physical chemistry of induced reactions (with radiations, particles and ultrasonics); Physical Sciences; Pyridones - chemistry; Reactivity and mechanisms; Science & Technology; Thiazoles - chemistry; Thiones - chemistry; OXYGEN; HYDROXYL RADICALS; ELECTRON; FLASH-PHOTOLYSIS; HYDROXYPYRIDINETHIONES; CELL-FREE; THIYL RADICALS; HYDROPEROXIDES; 2'-DEOXYGUANOSINE; DAMAGE; Nitrogen heterocycle; Thiazole derivatives; EPR spectrometry; Photo-induced transient spectroscopy; Photochemical reaction; Spin trapping; Pyridine derivatives; Pyrrole derivatives; Organic disulfide; Photolysis; Organic isothiocyanate; Reaction mechanism; Cleavage; Fenton reaction; Chemical synthesis; Oxygen sulfur heterocycle; Hydrogen transfer; Chemical rearrangement; Alkoxyl; Experimental study; Quantum yield; Ketone; Thione; Organic free radical; DNA; Photooxidation
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo025856w

UVA-irradiation of the photo-Fenton reagents N-isopropoxypyridone 2b and N-isopropoxythiazole-2(3H)-thione 3b releases radicals which induce strand breaks. Transient spectroscopy establishes N−O bond scission [ΦN - O = (75 ± 8)% for 2b and (65 ± 7)% 3b] as the dominating primary photochemical process to afford the DNA-damaging radicals. Product studies and laser-flash experiments reveal that the thiazolethione 3b leads primarily to the disulfide 5, from which through C−S bond breakage, the bithiazyl 6, the thiazole 7, and the isothiocyanate 8 are derived. Upon irradiation of pyridone 2b (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 N-oxide (DMPO) and EPR spectroscopy. In contrast, the photolysis of the thiazolethione 3b (350 nm) affords exclusively the DMPO adducts of the isopropoxyl radicals. Control experiments disclose that the thiazolethione-derived photoproduct disulfide 5, or the intermediary thiyl radicals 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 H2O−MeCN, the pyridone 2b and the thiazolethione 3b display moderate strand-break activity (17% open-circular DNA for 2b and 12% for 3b). In pure water, however, the pyridone 2b 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 3b derives presumably from isopropoxyl radicals, because only these are detected in the photolysis of this photo-Fenton reagent.