title: π-Radical to σ-Radical Tautomerization in One-Electron-Oxidized 1-Methylcytosine and Its Analogs.
abstract: In this work, iminyl σ-radical formation in several one-electron-oxidized cytosine analogs, including 1-MeC, cidofovir, 2'-deoxycytidine (dCyd), and 2'-deoxycytidine 5'-monophosphate (5'-dCMP), were investigated in homogeneous, aqueous (D2O or H2O) glassy solutions at low temperatures by employing electron spin resonance (ESR) spectroscopy. Upon employing density functional theory (DFT) (DFT/B3LYP/6-31G* method), the calculated hyperfine coupling constant (HFCC) values of iminyl σ-radical agree quite well with the experimentally observed ones, thus confirming its assignment. ESR and DFT studies show that the cytosine iminyl σ-radical is a tautomer of the deprotonated cytosine π-cation radical [cytosine π-aminyl radical, C(N4-H)(•)]. Employing 1-MeC samples at various pHs ranging from ca. 8 to 11, ESR studies show that the tautomeric equilibrium between C(N4-H)(•) and the iminyl σ-radical at low temperature is too slow to be established without added base. ESR and DFT studies agree that, in the iminyl σ-radical, the unpaired spin is localized on the exocyclic nitrogen (N4) in an in-plane pure p-orbital. This gives rise to an anisotropic nitrogen hyperfine coupling (Azz = 40 G) from N4 and a near isotropic β-nitrogen coupling of 9.7 G from the cytosine ring nitrogen at N3. Iminyl σ-radical should exist in its N3-protonated form, as the N3-protonated iminyl σ-radical is stabilized in solution by over 30 kcal/mol (ΔG = -32 kcal/mol) over its conjugate base, the N3-deprotonated form. This is the first observation of an isotropic β-hyperfine ring nitrogen coupling in an N-centered DNA radical. Our theoretical calculations predict that the cytosine iminyl σ-radical can be formed in double-stranded DNA by a radiation-induced ionization-deprotonation process that is only 10 kcal/mol above the lowest energy path.
authors.affiliation: Department of Chemistry, Oakland University , Rochester, Michigan 48309, United States.
authors.forename: Amitava
authors.initials: A
authors.lastname: Adhikary
authors.affiliation: Department of Chemistry, Oakland University , Rochester, Michigan 48309, United States.
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Chemistry, Oakland University , Rochester, Michigan 48309, United States.
authors.forename: Casandra T
authors.initials: CT
authors.lastname: Bishop
authors.affiliation: Department of Chemistry, Oakland University , Rochester, Michigan 48309, United States.
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Wiegand
authors.affiliation: Department of Chemistry, Oakland University , Rochester, Michigan 48309, United States.
authors.forename: Ragda M
authors.initials: RM
authors.lastname: Hindi
authors.affiliation: Department of Chemistry, Oakland University , Rochester, Michigan 48309, United States.
authors.forename: Ananya
authors.initials: A
authors.lastname: Adhikary
authors.affiliation: Department of Chemistry, Oakland University , Rochester, Michigan 48309, United States.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Sevilla
mesh_terms: D002412:Cations / Q000737:chemistry; D003080:Cold Temperature; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry; D004578:Electron Spin Resonance Spectroscopy; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry; D012996:Solutions / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D002412:Cations; D012996:Solutions; D014867:Water; C031532:1-methylcytosine; D003596:Cytosine; D009584:Nitrogen