title: Spirodi(iminohydantoin) products from oxidation of 2'-deoxyguanosine in the presence of NH4Cl in nucleoside and oligodeoxynucleotide contexts.
abstract: Upon oxidation of the heterocyclic ring in 2'-deoxyguanosine (dG), the initial electrophilic intermediate displays a wide range of reactivities with nucleophiles leading to many downstream products. In the present study, the product profiles were mapped when aqueous solutions of dG were allowed to react with NH4Cl in the presence of the photooxidants riboflavin and Rose Bengal as well as the diffusible one-electron oxidant Na2IrCl6. Product characterization identified the 2'-deoxyribonucleosides of spiroiminodihydantoin, 5-guanidinohydantoin, and oxazolone resulting from H2O as the nucleophile. When NH3 was the nucleophile, a set of constitutional isomers that are diastereotopic were also observed, giving characteristic masses of dG + 31. ESI(+)-MS/MS of these NH3 adducts identified them to be spirocycles with substitution of either the C5 or C8 carbonyl with an amine. The NH3 adducts exhibit acid-catalyzed hydrolysis to spiroiminodihydantoin. Quantification of the NH3 and H2O adducts resulting from oxidation of dG in the nucleoside, single-stranded, and duplex oligodeoxynucleotide contexts were monitored allowing mechanisms for product formation to be proposed. These data also provide a cautionary note to those who purify their oligonucleotide samples with ammonium salts before oxidation because this will lead to unwanted side reactions in which ammonia participates in product formation.
authors.affiliation: Department of Chemistry, University of Utah , 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Fleming
authors.forename: Erin I
authors.initials: EI
authors.lastname: Armentrout
authors.forename: Judy
authors.initials: J
authors.lastname: Zhu
authors.forename: James G
authors.initials: JG
authors.lastname: Muller
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Burrows
mesh_terms: D003849:Deoxyguanosine / Q000737:chemistry*; D006151:Guanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D006827:Hydantoins / Q000737:chemistry*; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D010084:Oxidation-Reduction; D013141:Spiro Compounds / Q000737:chemistry*; D053719:Tandem Mass Spectrometry
chemical_list: D006827:Hydantoins; D009705:Nucleosides; D009838:Oligodeoxyribonucleotides; D013141:Spiro Compounds; C408822:spiroiminodihydantoin; C544969:spiroiminodihydantoin nucleoside; D006151:Guanosine; D003849:Deoxyguanosine