个人简介

2005, PhD, Purdue University · 1996, BS, Wuhan University, China

研究领域

Mass spectrometry · Ion Chemistry · Bioanalytical chemistry · Proteomics

Mass spectrometry is a fascinating analytical and biological technology. Our research focuses on the new mass-spec innovation based on newly discovered ion chemistry and novel instrumentation. The current projects are: 1. Liquid sample DESI —- the Study of Electrochemistry, Protein Conformation and Reaction Kinetics by Mass Spectrometry We have extended the desorption electrospray ionization (DESI),1 an ambient ionization method, to the direct analysis of liquid samples. Due to its direct sampling and ionization properties, this Liquid Sample DESI-MS is versatile and has unique applications. For instance, it allows us to study electrochemistry, protein conformations, fast reaction kinetics, atmospheric pressure ion/molecule (or ion/ion) reactions, single droplet microextraction, etc.2-6 One of our recent effort is being devoted to coupling of electrochemistry (EC)2,3 with mass spectrometry using DESI as the interface for bioanalytical applications and for the investigation of mechanisms of reaction chemistry. For example, the generation of the perylene radical cation from the electro-oxidation of perylene and the electrolytic reduction of disulfide bonds of insulin in cell followed with online detection by DESI-MS. Due to the fast ionization feature, it can also been used to generate native protein ions from solutions with high sensitivity and to probe protein conformational changes in solution.5 For instance, the ionization of cytochrome c from water produce abundance native protein ions using DESI while traditional ESI gives unfolded ions. Based on the capability of desorption electrospray ionization (DESI) for direct and fast ionization of a high-speed liquid jet stream, we developed a microsecond time-resolved mass spectrometric method for fast kinetic study.7 The fast reaction of 2,6-dichlorophenolindophenol (DCIP) and L-ascobic acid (L-AA) was used to demonstrate this concept, and the pseudo-first order reaction rate constant was successfully measured with the time resolution down to 300 µs. The good agreement of the MS measured value of (116±3) s-1 with that measured by stopped-flow optical method (105±2) s-1 validates the feasibility of such as DESI-MS approach. Liquid sample DESI can be used to directly ionize large proteins (up to 150 kDa) and noncovalent protein complexes (> 45 kDa) preserving weak non-covalent interactions.8 Doping the DESI spray solvent with supercharging reagents resulted in the increased multiple charges without protein denaturation or complex dissociation. 2. Selenium Chemistry for Biological Thiol Derivatization Selenium reagents such as ebselen can be used to selectively and rapidly derivatize thiol peptides/proteins for mass spectrometric analysis.9 This reaction is highly selective, rapid, reversible and efficient. For instance, the Cysteine121 residue of β-lactoglubin A can be labeled using ebselen with quantitative conversion in 30 s 3. Protein footprinting using fast photolytic oxidation of protein (FPOP) method with various oxidants. Chemical footprinting of proteins has long been proven to be an efficient method for probing protein-protein interactions. FPOP10 achieves protein oxidation on a microsecond timescale, making it a strong candidate for protein footprinting. The objective of this project is to develop new FPOP methods with novel laser-generated oxidative chemical probes such as the highly oxidative sulfate radial anion SO4-▪. 4. Atmospheric pressure ion chemistry Tandem mass spectrometry is invaluable for chemical structure elucidation via examination of fragment ions after the activation and dissociation of gaseous precursor ions. Recently, an ambient ion thermal dissociation method11 has been established which allows the isolation and re-ionization of neutral fragments of peptide/protein ions at atmospheric pressure outside of the mass spectrometer. This method can also be used to seek green chemistry approaches in reaction methodology.12 For instance, ionic Borsche-Drechsel cyclization is feasible without the need for conventional acid catalysts.

近期论文

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Pengyuan Liu, Qiuling Zheng, Howard D. Dewald, Rebecca Zhou and Hao Chen*, The study of electrochemistry with ambient mass spectrometry, Trends in Analytical Chemistry, 2015, Accepted Yi Cai, Qiuling Zheng, Yong Liu, Roy Helmy, Joseph A. Loo and Hao Chen, "Integration of Electrochemistry with Ultra Performance Liquid Chromatography/Mass Spectrometry (UPLC/MS)", The 20th Anniversary Special Issue, Eur. J. Mass Spectrom., 2015, accepted. Fanpeng Kong, Bo Hu, Yan Gao, Kehua Xu*, Xiaohong Pan, Fang Huang, Qiuling Zheng, Hao Chen, Bo Tang*; “Fluorescence Imaging for Selenol in HepG2 Cell Apoptosis Induced by Na2SeO3”, Chem. Commun. 2015, 51, 3102-3105. Pengyuan Liu, R. G. Cooks*, and, Hao Chen*. “Nuclear Magnetic Resonance Structure Elucidation of Peptide b2 Ions”, Angew. Chem. Int. Ed., 2015, 54, 1547–1550. . Qiuling Zheng, Hao Zhang*, Lingying Tong, Shiyong Wu, Hao Chen*, "A New Cross-Linking Electrochemical Mass Spectrometry for Probing Protein 3D-Structures", Anal. Chem. 2014, Anal. Chem. 2014, 86, 8983-8991. Yi Cai, Yong Liu, Roy Hemly and Hao Chen*, “Coupling of Ultrafast LC Separation with Mass Spectrometry by DESI", J. Am. Soc. Mass Spectrom. 2014, 25, 1820-1823. Pengyuan Liu, Amanda Forni, Hao Chen*, “Development of Solvent-Free Ambient Mass Spectrometry for Green Chemistry Applications", Anal. Chem., 2014, 86, 4024-4032 Yijin Su, Mei Lu, Boliang Dong, Hao Chen,* Xiaodong Shi,* “Silver Catalyzed Alkyne Activation: the Surprising Ligand Effect”, Advanced Synthesis & Catalysis, 2014, 356, 692-696 . Pengyuan Liu, Jiang Zhang, Carly N. Ferguson, Hao Chen,* Joseph A. Loo,* “Measuring Protein-Ligand Interactions Using Liquid Sample Desorption Electrospray Ionization Mass Spectrometry”, Anal. Chem. 2013, 85, 11966−11972 . Yi Cai, Daniel Adams and Hao Chen*, A New Splitting Method for Both Analytical and Preparative LC/MS, J. Am. Soc. Mass Spectrom. 2014, 25, 286-292 . Pengyuan Liu, Mei Lu, Qiuling Zheng, Howard D. Dewald, Yun Zhang and Hao Chen*, “Recent Advances in Electrochemical Mass Spectrometry”, Analyst, 2013,138, 5519-5539 . Qiuling Zheng, Hao Zhang* and Hao Chen*, “Integration of Online Digestion and Electrolytic Reduction with Mass Spectrometry for Rapid Disulfide-Containing Protein Structural Analysis”, Int. J. Mass Spectrom. 2013, Volume 353, 1 November 2013, Pages 84–92 . Ismael Cotte-Rodriguez, Zhixin Miao, Yun Zhang and Hao Chen*, “Introduction to Protein Mass Spectrometry”, Characterization of Protein Therapeutics using Mass Spectrometry, Guodong Chen, Ed., Springer Science+Business Media New York, 2013, in press. Ning Pan, Pengyuan Liu, Weidong Cui, Bo Tang, Jingmin Shi and Hao Chen*, Highly Efficient Ionization of Phosphopeptides at Low pH by Desorption Electrospray Ionization Mass Spectrometry, Analyst, 2013, 138, 1321-1324.. Effie Weldy, Chloe Wolff, Zhixin Miao, Hao Chen*, “Selective and Sensitive Detection of Chromium (VI) in Waters Using Electrospray Ionization Mass Spectrometry”, Science & Justice, 2013, 53, 293-300. Mei Lu, J. Larry Campbell*, Rajat Chauhan, Craig A. Grapperhaus*, and Hao Chen*, “Probing the Reactivity and Radical Nature of Oxidized Transition Metal-Thiolate Complexes by Mass Spectrometry”, The Special Issue of Distonic Ions, J. Am. Soc. Mass Spectrom. 2013, 24, 502-512.. Yan Liu, Zhixin Miao, Rajeswari Lakshmanan, Rachel R. Ogorzalek Loo, Joseph A. Loo and Hao Chen*, Signal and Charge Enhancement for Protein Analysis by Liquid Chromatography-Mass Spectrometry with Desorption Electrospray Ionization, Eugene Nikolaev Honor Issue, Int. J. Mass Spectrom. 2012, 325-327, 161-166. Pengyuan Liu, Ingela T. Lanekoff, Julia Laskin*, Howard D. Dewald and Hao Chen*, The Study of Electrochemical Reactions Using Nanospray Desorption Electrospray Ionization-Mass Spectrometry, Anal. Chem. 2012, 84, 5737−5743. Zhenzhen Chen, Qingling Li, Qianqian Sun, Hao Chen, Xu Wang, Na Li, Miao Yin, Yanxia Xie, Hongmin Li, and Bo Tang*, Simultaneous Determination of Reactive Oxygen and Nitrogen Species in Mitochondrial Compartments of Apoptotic HepG2 Cells and PC12 Cells Based On Microchip Electrophoresis−Laser-Induced Fluorescence, Anal. Chem. 2012, 84, 4687–4694. Yun Zhang, Weidong Cui, Hao Zhang, Howard D. Dewald and Hao Chen*, Electrochemistry-Assisted Top-Down Characterization of Disulfide-Containing Proteins. Anal. Chem. 2012, 84, 3838–3842. .