title: Dimerization of ionized 4-(methyl mercapto)-phenol during ESI, APCI and APPI mass spectrometry.
abstract: A novel ion/molecule reaction was observed to occur under electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), and atmospheric pressure photo ionization (APPI) conditions, leading to dimerization of ionized 4-(methyl mercapto)-phenol followed by fast H(*) loss. The reaction is particularly favored during ESI, which suggests that this ion/molecule reaction can occur both in the solution inside the ESI-charged droplets and in the gas-phase environment of most other atmospheric pressure ionization techniques. The dimerization reaction is inherent to the electrolytic process during ESI, whereas it is more by ion/molecule chemistry in nature during APCI and APPI. From the tandem mass spectrometry (MS/MS) data, accurate mass measurements, hydrogen/deuterium (H/D) exchange experiments and density functional theory (DFT) calculations, two methyl sulfonium ions appear to be the most likely products of this electrophilic aromatic substitution reaction. The possible occurrence of this unexpected reaction complicates mass spectral data interpretation and can be misleading in terms of structural assignment as reported herein for 4-(methyl mercapto)-phenol.
authors.affiliation: Analytical Sciences, Chemical Development, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA. lianming.2.wu@gsk.com
authors.forename: Lianming
authors.initials: L
authors.lastname: Wu
authors.forename: Marcos N
authors.initials: MN
authors.lastname: Eberlin
authors.forename: Yuri E
authors.initials: YE
authors.lastname: Corilo
authors.forename: David Q
authors.initials: DQ
authors.lastname: Liu
authors.forename: Hao
authors.initials: H
authors.lastname: Yin
mesh_terms: D000465:Algorithms; D016477:Artifacts; D002851:Chromatography, High Pressure Liquid; D041961:Deuterium Exchange Measurement; D019281:Dimerization; D004340:Drug Contamination; D005609:Free Radicals; D009682:Magnetic Resonance Spectroscopy; D010636:Phenols / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013452:Sulfonium Compounds / Q000737:chemistry; D053719:Tandem Mass Spectrometry
chemical_list: D005609:Free Radicals; D010636:Phenols; D013438:Sulfhydryl Compounds; D013452:Sulfonium Compounds; C044702:4-(methylthio)phenol