Ohio University

Benjamin Bythell

Benjamin Bythell Profile Picture
Associate Professor
Clippinger 391
Clippinger 373 (lab)

Recent News

Education and Appointments

MChem., University of Bath, UK, 2002

Ph.D., Chemistry, Oregon State University, 2007

Postdoctoral Fellow, German Cancer Research Center, 2008-2010

Postdoctoral Fellow, National High Magnetic Field Laboratory, Florida State University, 2010-2013

Assistant Professor, University of Missouri, St. Louis, MO, 2013-2019

Google Scholar

Courses Taught

  • CHEM 5860 Advanced Analytical Chemistry

Research Interests

  • Chemistry of Useful Destruction  

My research directly addresses identification of chemical structure. I strive to understand the structure, reactivity, and gas-phase behavior of biologically-, medically-, forensically-, and industrially-important chemicals. Fundamentally, chemical structure determines the properties and potential functions of any given chemical. Thus, by accurately determining the chemical structure of unknown chemicals we can then determine their specific function(s). I use a combination of analytical, computational, and biophysical chemistry techniques in my research. Experimentally, I utilize tandem mass spectrometry, separations, and spectroscopy coupled with regiospecific labelling. I develop methods for greatly improved chemical characterization based on superior understanding of the key gas-phase chemistries involved in the diagnostic fragmentation of the relevant analyte ions. In tandem mass spectrometry-based approaches to chemical identification, each collection of fragment ions is characteristic of the specific precursor ion structure(s). By a process similar to retro-synthesis we leverage our understanding of the gas-phase chemistry to enable identification of the precursor ion. Understanding the gas-phase chemistry comes from the application of targeted computational approaches coupled to the experimental work to model the molecular ion “destruction” (custom molecular dynamics, density functional and ab initio calculations, and kinetic modeling). I have recently secured National Science Foundation (CHE-1808394) funds to support initial development of a method for characterization of complex carbohydrates (glycans) based on these principles (see publications 38, 40-43 for further details).  

Example complex carbohydrate (glycan) sequences and diversification points of human milk oligosaccharides and complex N glycans.
Example complex carbohydrate (glycan) sequences and diversification points of human milk oligosaccharides and complex N glycans.



The carbohydrate fragmentation nomenclature of Domon and Costello.
The carbohydrate fragmentation nomenclature of Domon and Costello.

My group has an active project on metabolite characterization and quantitation (NIH funded 1R01GM134081-01). This project uses a combination of analyte tagging with basic groups to improve reduce degeneracy (multiple ion types from one analyte) and greatly improve ionization efficiency. The newly generated multiply charged, tagged metabolites are then identified based on our understanding of their fragmentation chemistry. Our first publication while at Ohio University (48) demonstrates the approach. We are currently using this approach to identify new metabolites. 

We also have also recently pursued projects on i) characterization of petroleum components (publications 46, 29, and 22), ii) metal complexes (publications 34 and 35), and iii) protonated peptides (publications 37 and 33). We are actively open to collaborative work with other groups.  

The Bythell group is diverse and has included analytical, organic, physical, and biochemistry graduate students. Students learn a wide assortment of scientific approaches based around mass spectrometry (accurate mass identification, HPLC, isotopic labeling, tandem mass spectrometry, hydrogen/deuterium exchange, “action” IR spectroscopy), and cutting edge computational methods. In so doing, students acquire a wide variety of valuable skills, and are exposed to multiple approaches to problem-solving.  


I received a MChem. from Bath University, UK in 2002 and a Ph.D. from Oregon State University in 2007. After a postdoctoral fellowship at the German Cancer Research Center in Heidelberg, Germany, and the National High Magnetic Field Laboratory at Florida State University (2010-2013), I was hired as an Assistant Professor at the University of Missouri in St. Louis (UMSL). I was granted tenure at UMSL and promoted to Associate Professor in early 2019, before accepting my current position in the Department of Chemistry and Biochemistry at Ohio University. I am on the Editorial Board of the Journal of the American Society for Mass Spectrometry.

Selected Publications

(▲ indicates undergraduate co-author)

(48) Guan, S., Armbruster, M., Huang, T., Edwards, J.L., Bythell, B.J., Isomeric Differentiation and Acidic Metabolite Identification by Piperidine-based Tagging, LC-MS/MS, and Understanding of the Dissociation Chemistry, Analytical Chemistry, 2020, 92, 9305−9311, DOI: 10.1021/jasms.0c00074. 

(47) Guan, S., Rabus, J.M., Maître, P., Bythell, B.J., Gas-phase Structure and Fragmentation of Deprotonated RGD, Journal of the American Society for Mass Spectrometry, 2020. DOI: 10.1021/jasms.0c00074.  

 (46) Abutokaikah, M.T., Gnawali, G.R., Frye, J.W.,▲ Stump, C.M.,▲ Tschampel, J.,▲ Murphy, M.J.,▲  LaChance, E.S.,▲ Guan, S., Spilling, C.D., Bythell, B.J., Leaving Group Effects in a Series of Electrosprayed CcHhN1 Anthracene Derivatives, Journal of the American Society for Mass Spectrometry, 2019, DOI: 10.1007/s13361-019-02298-0.

(45) Morrison, K.A., Bythell, B.J., Clowers, B.H., Interrogating Gas-Phase Clustering of Organophosphonate Species via Atmospheric Flow Tube-Mass Spectrometry, Journal of the American Society for Mass Spectrometry, 2019, 30, 1308-1320. DOI: 10.1007/s13361-019-02202-w

(44) Huang, T.; Rabus, J.M.; Bythell, B.J.; Edwards, J.L., Fragmentation of Multi-Charged Derivatized Lysine using Nanospray CID Tandem Mass Spectrometry, Journal of the American Society for Mass Spectrometry, 2019, 30, 1158-1162, DOI: 10.1007/s13361-019-02154-1.

(43) Rabus, J.M.; Simmons, D.; Maitre, P.; Bythell, B.J., Deprotonated Carbohydrate Anion Fragmentation Chemistry: Structural Evidence from Tandem Mass Spectrometry, Infra-Red Spectroscopy, and Theory, Physical Chemistry Chemical Physics, 2018, 20, 27897 – 27909, DOI: 10.1039/C8CP02620C.

(42) Bythell, B.J.; Rabus, J.M.; Wagoner, A.R.;▲ Abutokaikah, M.T.; Maitre, P.; Sequence Ion Structures and Dissociation Chemistry of Deprotonated Sucrose Anions, Journal of the American Society for Mass Spectrometry, 2018, 29, 2380-2393, DOI: 10.1007/s13361-018-2065-0

(41) Abutokaikah, M.T.; Frye, J.;▲ Tschampel, J.;▲  Rabus, J.M.; Bythell, B.J., Fragmentation Pathways of Lithiated Hexose Monosaccharides, Journal of the American Society for Mass Spectrometry, 2018, 29, 1627–1637, DOI: 10.1007/s13361-018-1973-3

(40) Rabus, J.M.; Abutokaikah, M.T.; Ross, R.T.;▲ Bythell, B.J., Sodium-cationized Carbohydrate Gas-phase Fragmentation Chemistry: Influence of Glycosidic Linkage Position, Physical Chemistry Chemical Physics, 2017, 19, 25643-25652, DOI: 10.1039/C7CP04738J

(38) Bythell, B.J., Abutokaikah, M.T.; Wagoner, A.R.;▲ Guan, S.; Rabus, J.M., Cationized Carbohydrate Gas-phase Fragmentation Chemistry, Journal of the American Society for Mass Spectrometry, 2017, 28, 688-703, DOI: 10.1007/s13361-016-1530-x.

(37) Abutokaikah, M.T.; Guan, S.; Bythell, B.J., Stereochemical Sequence Ion Selectivity:  Proline vs. Pipecolic Acid-containing Protonated Peptides, Journal of the American Society for Mass Spectrometry, 2017, 28, 182-189, DOI: 10.1007/s13361-016-1510-1.

(35) Zhang, Y.; Quiggins, B.; Nguyen, H.;▲ Beedle, C.C.; Kovalev, A.E.; Clérac, R.; Hill, S.; Bythell, B.J.; Holmes, S.J., Structure-Property Relationships in Tricyanoferrate(III) Building Blocks and Trinuclear Cyanide-Bridged Complexes, European Journal of Inorganic Chemistry, 2016, 15-16, 2432–2442. DOI: 10.1002/ejic.201600199

(34)  Van Stipdonk, M.J.;  O’Malley, C.;▲  Plaviak, A.;▲  Martin, D.; Pestok, J.;▲  Mihm, P.A.;▲ Hanley, C.G.;▲ Corcovilos, T.A.; Gibson, J.K.;  Bythell, B.J., Dissociation of Gas-Phase, Doubly-Charged Uranyl-Acetone Complexes by Collisional Activation and Infrared Photodissociation, International Journal of Mass Spectrometry, 2016, 396, 22–34. DOI:

(33)  Nelson, C.R.;  Abutokaikah, M.T.; Harrison, A.G.; Bythell, B.J., Proton Mobility in b2 ion Formation and Fragmentation Reactions of Histidine-Containing Peptides, Journal of the American Society for Mass Spectrometry, 2016, 27, 487-497. DOI: 10.1007/s13361-015-1298-4

(29) Ruddy, B.M.;  Huettel, M.; Kostka, J.E.; Lobodin, V.V.; Bythell, B.J.; McKenna, A.M.; Aeppli,C.; Reddy, C.M.; Nelson, R.K..; Marshall, A.G.; Rodgers, R.P. Targeted Petroleomics: Analytical Investigation of Macondo Well Oil Oxidation Products from Pensacola Beach, Energy Fuels, 2014, 28 (6), 4043–4050.

(24) Scotcher, J.; Bythell, B.J.; Marshall, A.G. Unequivocal Determination of Site-Specific Protein Disulfide Bond Reduction Potentials by Top-down FT-ICR MS: Characterization of the N- and C-terminal Redox-Active Sites in Human Thioredoxin 1, Analytical Chemistry, 2013, 85, 9164-9172.

(22) Podgorski, D.C.; Corilo, Y.E.; Nyadong, L.; Lobodin, V.V.; Bythell, B.J.; Robbins, W.K.; McKenna, A.M.; Marshall, A.G.; Rodgers, R.P. Heavy Petroleum Composition. 5. Compositional and Structural Continuum of Petroleum Revealed, Energy and Fuels, 2013, 27, 1268–1276.