title: Electrospray ionization tandem mass spectrometry analysis of the reactivity of structurally related bromo-methyl-benzoquinones toward oligonucleotides.
abstract: We report the use of electrospray ionization tandem mass spectrometry (ESI-MS/MS) as a tool for rapid screening of structurally related chemicals toward oligonucleotides using the binding of five bromobenzoquinones with single-stranded (ss) and double-stranded (ds) oligonucleotides (ODNs) as a model. We found that these compounds interact differentially with oligonucleotides depending on the extent of their bromination and methylation. Three dibromobenzoquinones, 2,6-dibromo-1,4-benzoquinone (2,6-DBBQ), 2,5-dibromo-1,4-benzoquinone (2,5-DBBQ), and 2,5-dimethyl-3,6-dibromo-1,4-benzoquinone (DMDBBQ), bound to ssODN to form 1:1 adducts, and the binding constant of DMDBBQ bound to ssODN was 100-fold lower than those of 2,6-DBBQ and 2,5-DBBQ to ssODN, indicating that methyl groups hindered interactions of the bromoquinones with ODNs. Collision-induced dissociation (CID) of the 1:1 and 1:2 adducts of ODN with 2,6-DBBQ and 2,5-DBBQ demonstrated neutral loss of DBBQ and charge separations. Incubation of two tetrabromobenzoquinones (TBBQ), 2,3,5,6-tetrabromo-1,4-benzoquinone and 3,4,5,6-tetrabromo-1,2-benzoquinone, with the same ODNs did not form any adducts of TBBQ with ssODN or dsODN; however, bromide-ODNs were detected. Fragmentation of the bromide-ODN adducts showed loss of the HBr molecule, supporting the presence of bromide on ODNs. High-resolution MS and MS/MS analysis of the mixtures of dinucleotides (AA, GG, CC, and TT) and TBBQ confirmed the presence of bromide on the dinucleotides, supporting the transfer of bromide to ODNs through interaction with TBBQ. This study presents evidence of differential interactions of structurally related bromo and methyl-benzoquinones with oligonucleotides and demonstrates a potential application of ESI-MS/MS analysis of chemical interactions with ODN for rapid screening of the reactivity of other structurally related environmental contaminants toward DNA.
authors: Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors: Janna
authors: J
authors: Anichina
authors: Yuli
authors: Y
authors: Zhao
authors: Steve E
authors: SE
authors: Hrudey
authors: Andre
authors: A
authors: Schreiber
authors: Xing-Fang
authors: XF
authors: Li
mesh_terms: D016227:Benzoquinones / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D018736:DNA Adducts; D054879:Halogenation; D008745:Methylation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D014874:Water Pollutants, Chemical; D018508:Water Purification
chemical_list: D016227:Benzoquinones; D018736:DNA Adducts; D009838:Oligodeoxyribonucleotides; D014874:Water Pollutants, Chemical; D004247:DNA