Reactivity of Substituted Charged Phenyl Radicals toward Components of Nucleic Acids

• Published in: Journal of the American Chemical Society Vol. 125; no. 8; pp. 2272 - 2281
• Main Authors: Ramírez-Arizmendi, Luis E, Heidbrink, Jenny L, Guler, Leonard P, Kenttämaa, Hilkka I
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 26.02.2003
• Subjects: Adenine - chemistry; Analytical chemistry; Benzene Derivatives - chemistry; Biphenyl Compounds - chemical synthesis; Biphenyl Compounds - chemistry; Chemistry; Exact sciences and technology; Free Radicals - chemistry; Gases - chemistry; Nucleic Acids - chemistry; Spectrometric and optical methods; Thermodynamics; Thymine - analogs & derivatives; Thymine - chemistry; Uracil - analogs & derivatives; Uracil - chemistry; Hydrogen; Nucleoside; Gas phase; Structure; Ion cyclotron resonance; Mass spectrometry; Nucleic acid
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja020632g

Reactions of differently substituted phenyl radicals with components of nucleic acids have been investigated in the gas phase. A positively charged group located meta with respect to the radical site was employed to allow manipulation of the radicals in a Fourier-transform ion cyclotron resonance mass spectrometer. All of these electrophilic radicals react with sugars via exclusive hydrogen atom abstraction, with adenine and uracil almost exclusively via addition (likely at the C8 and C5 carbons, respectively), and with the nucleoside thymidine by hydrogen atom abstraction and addition at C5 in the base moiety (followed by elimination of •CH3). These findings parallel the reactivity of the phenyl radical with components of nucleic acids in solution, except that the selectivity for addition is different. Like HO•, the electrophilic charged phenyl radicals appear to favor addition to the C5-end of the C5−C6 double bond of thymine and thymidine, whereas the phenyl radical preferentially adds to C6. The charged phenyl radicals do not predominantly add to thymine, as the neutral phenyl radical and HO•, but mainly react by hydrogen atom abstraction from the methyl group (some addition to C5 in the base followed by loss of •CH3 also occurs). Adenine appears to be the preferred target among the nucleobases, while uracil is the least favored. A systematic increase in the electrophilicity of the radicals by modification of the radicals' structures was found to facilitate all reactions, but the addition even more than hydrogen atom abstraction. Therefore, the least reactive radicals are most selective toward hydrogen atom abstraction, while the most reactive radicals also efficiently add to the base. Traditional enthalpy arguments do not rationalize the rate variations. Instead, the rates reflect the radicals' electron affinities used as a measure for their ability to polarize the transition state of each reaction.