Aminyl Radical Generation via Tandem Norrish Type I Photocleavage, β-Fragmentation: Independent Generation and Reactivity of the 2'-Deoxyadenosin- N6-yl Radical.
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 × 105s-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.
Department of Chemistry, Johns Hopkins University , 3400 North Charles Street, Baltimore, Maryland 21218, United States.
Liwei
L
Zheng
Department of Chemistry & Biomolecular Sciences, University of Ottawa , 10 Marie Curie Pvt., Ottawa, Canada.
Markus
0000-0002-7810-1560
M
Griesser
Department of Chemistry & Biomolecular Sciences, University of Ottawa , 10 Marie Curie Pvt., Ottawa, Canada.
Derek A
0000-0002-7305-745X
DA
Pratt
Department of Chemistry, Johns Hopkins University , 3400 North Charles Street, Baltimore, Maryland 21218, United States.
Marc M
0000-0002-5786-6118
MM
Greenberg
D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry; D003839:Deoxyadenosines / Q000138:chemical synthesis* / Q000737:chemistry; D005609:Free Radicals / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D055668:Photochemical Processes
D000588:Amines; D003839:Deoxyadenosines; D005609:Free Radicals; C058118:2'-deoxyadenosine