title: Reactions of 5-methylcytosine cation radicals in DNA and model systems: thermal deprotonation from the 5-methyl group vs. excited state deprotonation from sugar.
abstract: OBJECTIVE
  To study the formation and subsequent reactions of the 5-methyl-2'-deoxycytidine cation radical (5-Me-2'-dC•(+)) in nucleosides and DNA-oligomers and compare to one-electron oxidized thymidine.
  
  
  METHODS
  Employing electron spin resonance (ESR), cation radical formation and its reactions were investigated in 5-Me-2'-dC, thymidine (Thd) and their derivatives, in fully double-stranded (ds) d[GC*GC*GC*GC*](2) and in the 5-Me-C/A mismatched, d[GGAC*AAGC:CCTAATCG], where C* = 5-Me-C.
  
  
  RESULTS
  We report 5-Me-2'-dC•(+) production by one-electron oxidation of 5-Me-2'-dC by Cl(2)•- via annealing in the dark at 155 K. Progressive annealing of 5-Me-2'-dC•(+) at 155 K produces the allylic radical (C-CH(2)•). However, photoexcitation of 5-Me-2'-dC•(+) by 405 nm laser or by photoflood lamp leads to only C3'• formation. Photoexcitation of N3-deprotonated thyminyl radical in Thd and its 5'-nucleotides leads to C3'• formation but not in 3'-TMP which resulted in the allylic radical (U-CH(2)•) and C5'• production. For excited 5-Me-2',3'-ddC•(+), absence of the 3'-OH group does not prevent C3'• formation. For d[GC*GC*GC*GC*](2) and d[GGAC*AAGC:CCTAATCG], intra-base paired proton transferred form of G cation radical (G(N1-H)•: C(+ H(+))) is found with no observable 5-Me-2'-dC•(+) formation. Photoexcitation of (G(N1-H)•:C(+ H(+))) in d[GC*GC*GC*GC*](2) produced only C1'• and not the expected photoproducts from 5-Me-2'-dC•(+). However, photoexcitation of (G(N1-H)•:C(+ H(+))) in d[GGAC*AAGC:CCTAATCG] led to C5'• and C1'• formation.
  
  
  CONCLUSIONS
  C-CH(2)• formation from 5-Me-2'-dC•(+) occurs via ground state deprotonation from C5-methyl group on the base. In the excited 5-Me-2'-dC•(+) and 5-Me-2',3'-ddC•(+), spin and charge localization at C3' followed by deprotonation leads to C3'• formation. Thus, deprotonation from C3' in the excited cation radical is kinetically controlled and sugar C-H bond energies are not the only controlling factors in these deprotonations.
authors.affiliation: Department of Chemistry, Oakland University , Rochester, MI , USA.
authors.forename: Amitava
authors.initials: A
authors.lastname: Adhikary
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Palmer
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Todd
authors.forename: Alicia N
authors.initials: AN
authors.lastname: Heizer
authors.forename: Michael D
authors.initials: MD
authors.lastname: Sevilla
mesh_terms: D044503:5-Methylcytosine / Q000737:chemistry / Q000528:radiation effects; D002412:Cations / Q000737:chemistry / Q000528:radiation effects; D004247:DNA / Q000737:chemistry* / Q000528:radiation effects*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000737:chemistry / Q000528:radiation effects; D005720:Gamma Rays; D008956:Models, Chemical; D011522:Protons
chemical_list: D002412:Cations; D005609:Free Radicals; D011522:Protons; D044503:5-Methylcytosine; D004247:DNA
keywords: 5-Methylcytosine; DNA-oligomers; ESR; HFCC values; TD-DFT calculations; cation radical; one-electron oxidation; thymidine