title: Gas-Phase Unimolecular Dissociation Reveals Dominant Base Property of Protonated Homocysteine Sulfinyl Radical Ions.
abstract: Homocysteine sulfinyl radical ((SO⋅) Hcy) is a reactive intermediate involved during oxidative damage of DNA in the presence of high concentrations of homocysteine (Hcy). The short lifetime of (SO⋅) Hcy makes its preparation, isolation, and characterization challenging using traditional chemical measurement tools. Herein, we demonstrate the first study on mass-selected protonated (SO⋅) Hcy ions in the gas phase by investigating its unimolecular dissociation pathways from low energy collision-induced dissociation (CID). Tandem mass spectrometry (MS/MS), stable-isotope labeling, and theoretical calculations were employed to rationalize the observed fragmentation pathways. The dominant dissociation channel of protonated (SO⋅) Hcy was a charge-directed H2 O loss from the protonated sulfinyl radical (-SO⋅) moiety, forming a thiyl radical (-S⋅), which further triggered sequential radical-directed ⋅SH loss through multiple pathways. Compared to cysteine sulfinyl radical ((SO⋅) Cys), the small structural change induced by one additional methylene group in the side chain of (SO⋅) Hcy significantly promotes its base property while reducing the radical reactivity of sulfinyl radical. This observation provides new insight into studying reactions of (SO⋅) Hcy with biomolecules, which are critical in understanding toxicity induced by high levels of Hcy in biological conditions.
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, IN, 47907-2084, USA.
authors.forename: Chasity B
authors.initials: CB
authors.lastname: Love-Nkansah
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, IN, 47907-2084, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Chemistry and Department of Earth, Atmospheric, Planetary Sciences, Purdue University, West Lafayette, IN, 47907-2084, USA. francisc@purdue.edu.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Francisco
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, IN, 47907-2084, USA. yxia@purdue.edu.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
mesh_terms: D004249:DNA Damage; D005609:Free Radicals / Q000737:chemistry*; D005740:Gases / Q000737:chemistry*; D006710:Homocysteine / Q000737:chemistry* / Q000378:metabolism; D007477:Ions / Q000737:chemistry*; D008958:Models, Molecular; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013452:Sulfonium Compounds / Q000737:chemistry*; D053719:Tandem Mass Spectrometry
chemical_list: D005609:Free Radicals; D005740:Gases; D007477:Ions; D013438:Sulfhydryl Compounds; D013452:Sulfonium Compounds; D006710:Homocysteine
keywords: collision-induced dissociation; homocysteine; isotopic labeling; mass spectrometry; sulfinyl radical