Michael Van Stipdonk, Associate Professor of Chemistry
Ph.D., Texas A&M University
B.A. University of Detroit
Analytical and Biological Mass Spectrometry

Awards and Honors

• National Science Foundation Faculty Early Career Development (CAREER) Award, 2003
• Kansas Biomedical Infrastructure Network Faculty Scholar Award, 2003
• Wichita State University Young Faculty Scholar, 2004

Tel: 316.978.7381
Fax: 316.978.3431
Email: Mike.VanStipdonk@wichita.edu

RESEARCH PROGRAM SUMMARY

Undergraduate and graduate students in the van Stipdonk research group use ion trap mass spectrometry to study a variety of chemical processes in the gas-phase. As summarized below, our current research projects can be grouped into three general areas: (a) fundamental studies of peptide ion dissociation to support application of tandem mass spectrometry (tandem MS) to peptide and protein identification in proteomics; (b) studies of the intrinsic stability and reactivity of metal ion complexes important to biology, energy production and the environment, and (c) vibrational spectroscopy of gas-phase ions using wavelength-selective infrared multiple-photon photodissociation. Besides extensive use of mass spectrometry and tandem MS, work in our laboratory involves the synthesis of model molecules and peptides, including those with isotope labels, and use of density functional theory (DFT) to predict ion structures, energies and vibrational spectra. Our work on tandem MS and peptide dissociation has been funded by the National Science Foundation (NSF), the State of Kansas NSF EPSCoR program and the Kansas Biomedical Research Infrastructure Network. Studies of intrinsic metal ion chemistry have been supported by the U.S. Department of Energy and the Idaho National Laboratory. Work on ion spectroscopy is supported in part by the NSF, the FOM Instituut voor Plasmafysica “Rijnhuizen”, and the Nederlandse Organisatie voor Wetenschappelijk Onderzoek. In 8 years, the experiments in these areas at Wichita State have led to 55 manuscripts published or submitted for publication in peer-reviewed journals such as Journal of Physical Chemistry A, Journal of the American Society for Mass Spectrometry, Physical Chemistry-Chemical Physics and the Journal of the American Chemical Society. 15 more manuscripts are currently in preparation for submission.

Fundamental studies of peptide dissociation using tandem mass spectrometry

Mass spectrometry (MS) and tandem MS are the principal analytical tools used to identify peptides and proteins in proteomics. One focus of our research program is to improve protein and peptide identification by optimizing multiple-stage tandem MS approaches to sequence determination. In proteomics, collision-induced dissociation (CID) of protonated peptides is used to identify peptides, either directly through an interpretation of fragmentation patterns, or indirectly using comparison to fragment ion spectra in databases. For direct sequence determination, however, CID of metal [alkali and Ag(I)] cationized peptides offers potential advantages, particularly when coupled with multiple-stage tandem MS experiments. Our work in this area has demonstrated that sequence, choice of cationizing agent (proton or metal ion), and modification of the N-terminus all significantly influence the CID pathways of model peptides. Optimization of the multiple-stage tandem MS method is therefore critical if the unparalleled combination of speed, sensitivity and selectivity of MS is to be applied to its fullest potential to accurate identification of peptides and proteins in proteome studies.

When using tandem MS, the signal that we interpret, and use to determine structure and composition is provided by chemical (fragmentation) reactions. Accuracy in structure and composition assignment, therefore, depends on accurate interpretation of this chemical signal. A second objective of our research program is to provide a better understanding of gas-phase peptide dissociation mechanisms. In this work solid-phase synthesis is used to create model peptides that allow us to investigate the importance of cyclization and intramolecular nucleophillic attack to several proposed mechanistic pathways. Relative collision energies required to activate various pathways are measured, and the influence of structure and sequence on these energies established. We also make extensive use of isotope labeling and novel “tracer” experiments to investigate the proton migration and transfer in dissociation reactions. Experimental studies are supported by DFT computational investigation of probable reaction intermediates and mechanisms.

Representative publications:

1. Sequence Scrambling Fragmentation Pathways of Protonated Peptides, C. Bleiholder, S. Osburn, A. B. Young, S. Suhai, M. Van Stipdonk, A. G. Harrison, B. Paizs, J. Am. Chem. Soc. 130, 17774-17789 (2008).
2. Structure and Reactivity of an and a_n^* Ions Investigated using Isotope labeling, Tandem Mass Spectrometry and Density Functional Theory Calculations, B. Bythell, S. Molesworth, S. Osburn*, T. Cooper, B. Paizs and M. Van Stipdonk, J. Am. Soc. Mass Spectrom., 19, 1788-1798 (2008).
3. Formation of (b₃-1+cat)⁺ Ions from Metal-cationized Tetrapeptides Containing b-alanine, g-aminobutyric acid or e-aminocaproic Acid Residues, S. M. Osburn, S. O. Ochola, E. R. Talaty and M. J. Van Stipdonk, J. Mass Spectrom., 43, 1458-1469 (2008).
4. Influence of a 4-aminomethylbenzoic acid Residue on Competitive Fragmentation Pathways during CID of Metal Cationized Peptides, S. Osburn, S. Ochola, E. Talaty and M. Van Stipdonk, Rapid Comm. Mass Spectrom. 21, 3409-3419 (2007).
5. Collision-induced dissociation of Protonated Tetrapeptides Containing b-Alanine, g-Aminobutyric Acid, e-Aminocaproic Acid or 4-Aminomethylbenzoic Acid Residues, E. R. Talaty, T. J. Cooper, S. M. Osburn and M. J. Van Stipdonk, Rapid Comm. Mass Spectrom., 20, 3443-3455 (2006).
6. Isotope Labeling and Theoretical Study of the Formation of a₃^* Ions from Protonated Tetraglycine, T. J. Cooper, E. Talaty, J. Grove, S. Suhai, B. Paizs and M. J. Van Stipdonk, J. Am. Soc. Mass Spectrom. 17, 1654-1664 (2006).
7. Investigation of Intra-molecular Proton Migration in a Series of Model, Metal-Cationized Tripeptides Using In-situ Generation of an Isotope Label, K. Bulleigh, A. Howard, T. Do, Q. Wu, V. Anbalagan and M. Van Stipdonk, Rapid Comm. Mass Spectrom. 20, 227-232 (2006).
8. Novel Fragmentation Pathway for CID of (b_n-1+Cat)⁺ Ions from Model, Metal Cationized Peptides, T. J. Cooper, E. R. Talaty and M. J. Van Stipdonk, J. Am. Soc. Mass Spectrom. 16, 1305-1310 (2005).

Intrinsic stability and reactions of gas-phase metal ion complexes

In the dynamic realm of solution-phase coordination chemistry, formation and stability of complexes is controlled by coordination, geometry, oxidation state, and cooperative effects between different ligands. Probing these aspects provides glimpses of general metal ion chemistry, which leads to an understanding of electronic structure and bonding preferences that could eventually be exploited in new chemical reactions and processes.

The solution-phase environment of metal ions can be complicated, and changes in speciation are necessarily multiple-step reactions that involve participation of many mixed-ligand species, which undergo dissociation and ligand addition on a continuous basis. In this complex environment it is nearly impossible to probe chemistry in a species-explicit fashion, and hence conclusions derived from solution-phase studies tend to be statistical descriptions. Our experimental approach to overcome this problem is to move the investigations into the gas-phase environment of an ion-trap mass spectrometer (ITMS), and slow down chemical reactions to allow specific metal ion complexes to be studied explicitly.

In this part of our research program, the tandem mass spectrometry capabilities of the ITMS are used to elucidate complex structure, determine relative stability and to probe general patterns in chemical reactivity. These studies rely on our ability to transfer metal ion complexes from solution using electrospray ionization (ESI) or from surfaces by ion-induced sputtering, to a low pressure gas-phase environment. Here, ions can be selectively isolated and stored for time periods ranging from milliseconds to seconds. After isolation of a particular ion, composition and structure can be inferred, and stability is measured, using collision-induced dissociation. Ion reactivity can instead be investigated by allowing stored ions to interact with neutral reagents introduced into the ITMS. Beyond providing fascinating details about intrinsic metal complex chemistry, the results of the ITMS experiments on explicitly defined complexes permit direct “apples-to-apples comparisons” with those derived from theoretical (in our case, DFT) calculations. The main focus of our experimental work in this area is on the intrinsic chemistry (dissociation and ligand addition) of complexes that contain first-row transition metals, lanthanides or the uranyl ion.

Representative publications:

1. 2-Electron 3-Atom Bond in Side-on (η²) Superoxo Complexes: U(IV) and U(V) Dioxo Monocations, V. S. Bryantsev, K. C. Cossel, M. S. Diallo, W. A. Goddard, III, W. A. de Jong, G. S. Groenewold, W. Chien and M. J. Van Stipdonk, J. Phys. Chem. A, 112, 5777-5780 (2008).
2. Relative Metal Nucleophilicities of Diphenyldithiophosphinate Ligands using Gas-phase Dissociation Reactions, C. M. Leavitt*, G. L. Gresham, J.-J. Gaumet, D. Peterman, J. Klaehn, M. T. Benson, F. Aubriet, M. J. Van Stipdonk and G. S. Groenewold, Inorg. Chem., 47, 3056-3064 (2008).
3. Generation of Gas-phase VO²⁺, VOOH⁺ and VO₂⁺-Nitrile Complex Ions by Electrospray Ionization and Collision-induced Dissociation, Z. Parsons, C. Leavitt, T. Duong, G. S. Groenewold, G. L. Gresham and M. J. Van Stipdonk, J. Phys. Chem. A, 110, 11627-11635 (2006).
4. Gas-phase Uranyl-Nitrile Complex Ions, M. J. Van Stipdonk, W. Chien, K. Bulleigh, Q. Wu and G. S. Groenewold, J. Phys. Chem. A. 110, 959-970 (2006).
5. Binding of Molecular O₂ to Di- and Tri-Ligated [UO₂]⁺, G. S. Groenewold, K. C. Cossel, G. L. Gresham, A. K. Gianotto, A. D. Appelhans, J. E. Olson, M. J. Van Stipdonk, and W. Chien, J. Am. Chem. Soc. 128, 3075-3084 (2006).
6. Gas-phase Complexes Containing the Uranyl Ion and Acetone, M. J. Van Stipdonk, W. Chien, V. Anbalagan, K. Bulleigh*, D. Hanna and G. S. Groenewold, J. Phys. Chem. A. 108, 10448-10457 (2004).
7. Oxidation of 2-Propanol Ligands following Collision-induced Dissociation of a Gas-phase Uranyl Complex, M. J. Van Stipdonk, W. Chien, V. Anbalagan, G. L. Gresham and G. S. Groenewold, Int. J. Mass Spectrom. 237, 175-183 (2004).
8. Intrinsic Hydration of Uranyl-Hydroxide, -Nitrate and –Acetate Complexes, W. Chien, D. Hanna, V. Anbalagan, G. Gresham, G. Groenewold, M. Zandler and M. J. Van Stipdonk, J. Am. Soc. Mass Spectrom. 15, 777-783 (2004).

Vibrational spectroscopy of gas-phase ions using wavelength-selective Infrared Multiple Photon Photodissociation (IRMPD)

A general limitation of our gas-phase experimental approaches to study intrinsic chemistry is that no direct structural information is produced. Mass spectrometers provide only a mass-to-charge ratio and limited information regarding the connection of atoms. Determinations of structure therefore rely heavily either on chemical intuition or theoretical calculations. To fully explain and understand gas-phase reactivity, more definitive assessments of structure are needed. An ideal source of structural information would be a vibrational spectrum, but collection of a conventional linear absorption is often impracticable because the concentrations of “absorber” ions in the gas phase are too low. A solution to this problem is to use infrared multiple-photon photodissociation (IRMPD), in which an ion of interest is isolated in an ITMS and then irradiated using a tunable infrared wavelength laser. In this “action-spectroscopy” approach, resonant absorption of a photon is followed by intramolecular vibrational energy redistribution, and because radiative cooling is slow, rapid absorption of multiple photons raises the internal energy up to and beyond dissociation thresholds. Using IRMPD, precursor and product ion intensities can be measured as a function of photon wavelength to provide an infrared spectrum.

Our group recently began using IRMPD to produce infrared spectra of a range of gas-phase peptide ions and metal ion complexes. These experiments are conducted at the Free Electron Laser for Infrared eXperiments (FELIX) facility located at the FOM Instituut voor Plasmafysica “Rijnhuizen” in The Netherlands. The FELIX free-electron laser is capable of producing a high intensity beam of light that is tunable across the mid-IR region, and is interfaced to a Fourier-transform ion cyclotron resonance, ion-trapping mass spectrometer. Using IRMPD, our group, in collaboration with scientists at the Idaho National Laboratory and the Molecular Dynamics group at FOM, generated the first infrared spectra of discrete uranyl complex ions, uranyl and europium nitrate anions, and vanadyl complexes. In addition, we have developed a novel “functional group tagging” approach to study the intrinsic conformation of gas-phase peptide ions.

Representative publications:

1. IRMPD Spectroscopy of Anionic Group II Metal Nitrate Clustersb, C. M. Leavitt*, J. Oomens, R. P. Dain*, J. D. Steill, G. S. Groenewold and M. J. Van Stipdonk, J. Am. Soc. Mass Spectrom., (2009), in press (doi:10.1016/j.jasms.2008.12.023).
2. Spectroscopic Evidence for an Oxazolone Structure of the b₂ Fragment Ion from Protonated Tri-alanine, J. Oomens, S. Young, S. Molesworth and M. van Stipdonk, J. Am. Soc. Mass Spectrom., 20, 334-339 (2009).
3. Spectroscopic Investigation of H Atom Transfer in a Gas-phase Dissociation Reaction: McLafferty Rearrangement of Model Gas-phase Peptide Ions, M. J. Van Stipdonk, D. R. Kerstetter, C. M. Leavitt, G. S. Groenewold, J. D. Steill and J. Oomens, Phys. Chem.-Chem. Phys., 10, 3209-3221 (2008).
4. Infrared Multiple-photon Photodissociation of Gas-phase Group II Metal-nitrate Anions, J. Oomens, L. Myers, R. Dain, C. Leavitt, V. Pham, G. Gresham, G. Groenewold and M. Van Stipdonk, Int. J. Mass Spectrom. 273, 24-30 (2008).
5. Vibrational Spectroscopy of Anionic Nitrate Complexes of UO₂²⁺ and Eu³⁺ Isolated in the Gas Phase, G. S. Groenewold, J. Oomens, W. A. de Jong, G. L. Gresham, M. E. McIlwain and M. J. Van Stipdonk, Phys. Chem.-Chem. Phys., 10, 1192-1202 (2008).
6. Infrared Spectroscopy of Discrete Uranyl Anion Complexes, G. S. Groenewold, A. K. Gianotto, M. E. McIlwain, M. J. Van Stipdonk, M. Kullman, T. J. Cooper, D. T. Moore, N. Polfer and J. Oomens, J. Phys. Chem. A, 112, 508-521 (2008).
7. Mid-infrared Vibrational Spectra of Gas-phase, Acetone Ligated Cerium Hydroxide Cation, G. S. Groenewold, A. K. Gianotto, K. C. Cossel, M. J. Van Stipdonk, J. Oomens, N. Polfer, D. T. Moore and W. A. de Jong, Phys. Chem.-Chem. Phys., 9, 596-606 (2007).
8. Vibrational Spectroscopy of Mass Selected [UO₂(ligand)_n]²⁺ Complexes in the Gas Phase: Comparison with Theory, G. S. Groenewold, A. K. Gianotto, K. C. Cossel, M. J. Van Stipdonk, D. T. Moore, N. Polfer, J. Oomens, W. A. de Jong, and L. Visscher, J. Am. Chem. Soc. 128, 4802-4813 (2006).