title: Online Investigation of Aqueous-Phase Electrochemical Reactions by Desorption Electrospray Ionization Mass Spectrometry.
abstract: Electrochemistry (EC) combined with mass spectrometry (MS) is a powerful tool for elucidation of electrochemical reaction mechanisms. However, direct online analysis of electrochemical reaction in aqueous phase was rarely explored. This paper presents the online investigation of several electrochemical reactions with biological relevance in the aqueous phase, such as nitrosothiol reduction, carbohydrate oxidation, and carbamazepine oxidation using desorption electrospray ionization mass spectrometry (DESI-MS). It was found that electroreduction of nitrosothiols [e.g., nitrosylated insulin B (13-23)] leads to free thiols by loss of NO, as confirmed by online MS analysis for the first time. The characteristic mass shift of 29 Da and the reduced intensity provide a quick way to identify nitrosylated species. Equally importantly, upon collision-induced dissociation (CID), the reduced peptide ion produces more fragment ions than its nitrosylated precursor ion (presumably the backbone fragmentation cannot compete with the facile NO loss for the precursor ion), thus facilitating peptide sequencing. In the case of saccharide oxidation, it was found that glucose undergoes electro-oxidation to produce gluconic acid at alkaline pH, but not at neutral and acidic pHs. Such a pH-dependent electrochemical behavior was also observed for disaccharides such as maltose and cellobiose. Upon electrochemical oxidation, carbamazepine was found to undergo ring contraction and amide bond cleavage, which parallels the oxidative metabolism observed for this drug in leucocytes. The mechanistic information of these redox reactions revealed by EC/DESI-MS would be of value in nitroso-proteome research and carbohydrate/drug metabolic studies.
authors.affiliation: Center for Intelligent Chemical Instrumentation, Department of Chemistry and Biochemistry, Edison Biotechnology Institute, Ohio University, Athens, OH, 45701, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Process and Analytical Chemistry, Merck Research Laboratories, Merck and Co., Inc., Rahway, NJ, 07065, USA. yong_liu2@merck.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Process and Analytical Chemistry, Merck Research Laboratories, Merck and Co., Inc., Rahway, NJ, 07065, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Helmy
authors.affiliation: Department of Process and Analytical Chemistry, Merck Research Laboratories, Merck and Co., Inc., Rahway, NJ, 07065, USA.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Martin
authors.affiliation: Center for Intelligent Chemical Instrumentation, Department of Chemistry and Biochemistry, Edison Biotechnology Institute, Ohio University, Athens, OH, 45701, USA.
authors.forename: Howard D
authors.initials: HD
authors.lastname: Dewald
authors.affiliation: Center for Intelligent Chemical Instrumentation, Department of Chemistry and Biochemistry, Edison Biotechnology Institute, Ohio University, Athens, OH, 45701, USA. chenh2@ohio.edu.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
mesh_terms: D002220:Carbamazepine / Q000737:chemistry; D002241:Carbohydrates / Q000737:chemistry; D004563:Electrochemistry / Q000379:methods*; D008956:Models, Chemical; D010084:Oxidation-Reduction; D026403:S-Nitrosothiols / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D002241:Carbohydrates; D026403:S-Nitrosothiols; D002220:Carbamazepine
keywords: Carbohydrate oxidation; Desorption electrospray ionization; Electrochemistry; Mass spectrometry; Nitrosothiol reduction