Research in the Rodgers group is interdisciplinary in nature, making use of state-of-the-art physical and analytical techniques to study research problems that span all five disciplines of chemistry (i.e., analytical, biochemistry, inorganic, organic, and physical). However, most of the research projects we pursue are of either biological or inorganic relevance and involve the use of model systems. Our research efforts are generally aimed at achieving a better understanding of the interplay between structure and function in biological systems, or structure and intrinsic reactivity in inorganic systems. To this end, we make use of a variety of tandem mass spectrometry (MS/MS) approaches, often enhanced and supported by synergistic theoretical electronic structure calculations, in our research studies.
The primary tools of our research are tandem mass spectrometers (MS/MS) and computers.
We currently have three MS/MS instruments available in our experimental arsenal.
Guided Ion Beam Tandem Mass Spectrometery. Our first MS/MS instrument is a custom-built guided ion beam tandem mass spectrometer (GIBMS) of the BOQ geometry (magnetic sector (B) - octopole ion guide (O) - quadrupole mass filter (Q)). This instrument is designed to allow the kinetic-energy dependence of ion-molecule reactions (IMR) or collision-induced dissociation (CID) processes to be examined from thermal to hyperthermal energies. Measured reactant and product intensities are converted to absolute IMR or CID cross sections using Beer’s law. Cross sections are analyzed to extract accurate thermochemical data (i.e., bond dissociation energies (BDEs), activation energies (AEs), and heats of reaction (ΔHrxns). These measurements are supported by complementary theoretical calculations to provide molecule parameters needed for the analysis of experimental data and theoretical estimates for the quantities measured.
Fourier Transform Ion Cyclotron Resonance Mass Spectrometry. Our next MS/MS instrument is a Bruker 7T Solarix Hybrid FTMS (Q-FT-ICR MS). This instrument is our flagship mass spectrometer capable of very high mass accuracy and mass resolution measurements. It is equipped with a variety of ionization sources including: (1) electrospray ionization (ESI) and nano-ESI, (2) matrix assisted laser desorption ionization (MALDI), and (3) chemical ionization (CI and n-CI). It is also equipped with a variety of activation methods including: CID (in-source, Q-CID, SORI-CID), ion-ion reactions (ETD and PTR), ion-electron reactions (ECD and EDD), and photodissociation (IRMPD). It can also be used to perform MS imaging of biological tissues and analytically prepared surfaces in combination with the MALDI source. As a trapping mass spectrometer, it can also be used to make kinetic (e.g., IMR and H/D exchange), equilibrium (e.g., acid-base, ligand exchange, and clustering reactions), and spectroscopic (in combination with our tunable OPO IR laser system) measurements under well-controlled conditions.
Quadrupole Ion Trap Mass Spectrometry. Our third MS/MS instrument is a Bruker amaZon ETD quadrupole ion trap mass spectrometer (QITMS). This instrument possesses several of the same capabilities as our FT-ICR MS, but is not capable of nearly as high of mass accuracy or mass resolution measurements. It is equipped with two ionization sources including: (1) ESI and (2) CI and n-CI. It is also equipped with a variety of activation methods including: (1) CID (in-source and multiple collision-CID), (3) ETD and PTR, and (4) IRMPD. Like the FT-ICR MS it is also a trapping MS, and thus can also be used to make kinetic (e.g., IMR and H/D exchange), equilibrium (e.g., acid-base, ligand exchange, and clustering reactions), and spectroscopic (in combination with tunable lasers) measurements, but under somewhat less well controlled conditions than in the FT-ICR MS.
We also have three high performance liquid chromatographs (HPLC) that can be used independently or in combination with our commercial MS/MS instruments. A variety of supporting tools and instrumentation are also available including: (1) small analytical instruments for sample cleanup and preparation, (2) infrared lasers for complementary photodissociation or spectroscopic studies, (3) software packages for data analysis, and instrument design and control, (4) test and measurement electronics for diagnostics and control, and (5) mechanical tools and hardware. Our research sometimes involves instrument development and modification projects to enable improved MS/MS analyses. We collaborate extensively and thus make use of other MS and laser instrumentation available in the laboratories of our collaborators. Our computational efforts are primarily supported by the Wayne State University High Performance Grid and supplemented by PCs and workstations available in our laboratory. We make extensive use of two commercial computational chemistry software packages to perform relevant molecular dynamics simulations and electronic structure theory calculations: (1) the Gaussian suite of programs and (2) Hyperchem Professional.
Biomolecule Structure and Stability. Current research projects involve the study of the influence of the local environment (probed via deprotonation, protonation and noncovalent interactions with metal cations or binding of ligand and drug molecules) on the structures and stabilities of biologically relevant systems, and in particular, nucleic acids and their component building blocks (nucleobases, nucleosides and phosphate esters and including modifications), but we are also interested in proteins and their component building blocks (amino acids, peptides, and including post-translational modifications), and carbohydrates and their component building blocks. The mechanisms, energetics and control of fundamental dissociation processes that occur in these systems and the effects of solvation on these systems are also of interest. We are particularly interested in glycosidic and phosphate ester bond stability. These studies may lead to a better understanding of various metabolic pathways, provide information to help improve both solution and gas-phase MS/MS sequencing techniques, and facilitate the development of new drug candidates.
Molecular Recognition. Current research projects involve the study of the factors that lead to strong and selective binding of cations, anions, and various types of ligands as well as base-pairing interactions. Structure, size, charge, and the nature and number of donor-acceptor interactions all play a role in determining selectivity of binding and thus are examined. In particular, interactions with macrocyclic ligands and those that lead to noncanonical structures (e.g., the DNA i-motif or G-quadrupolexes) in biological systems are of interest. These studies may help improve characterization, separations, and drug delivery applications.
Solvation. Solvated systems are also being studied to enhance our understanding of the effects of solvation on biochemical processes, to provide insight into folding and conformational stability of biological macromolecules, the energetics of solvation, and structural information on the solvated complex. This work also connects the gas-phase tandem MS/MS studies to those performed in condensed-phase environments.
Clusters. Clusters are also being studied to examine how structure, stability, and dissociation dynamics vary with the size and nature and number of ligands or cation-anion pairs. What leads to enhanced stability or so-called magic number clusters?
Top-Down MS/MS Sequencing. Current research projects involve the development of methods to determine the primary sequence of intact RNAs and RNA-ligand complexes and the site(s) of binding. Methods to optimize the charge-state distribution produced, eliminate alkali metal cation adduction, and optimize sequence coverage while preserving biologically-relevant information are all a part of this effort.
Theoretical Calculations. Theoretical calculations are performed to support and enhance our experimental work. The calculations provide model structures and energetics for the species and processes under investigation, insight into the reaction or dissociation mechanisms, and the molecular parameters and IR spectra needed for analysis of our experimental data.
"Influence of 2'-Fluoro Modification on N-Glycosidic Bond Stabilities and Gas-Phase Ion Structures of Protonated Pyrimidine Nucleosides", Zachary J. Devereaux, H. A. Roy, C. C. He, Y. Zhu, N. A. Cunningham, L. A. Hamlow, G. Berden, J. Oomens, and M. T. Rodgers, J. Fluorine Chem. 219, 10-22 (2019). doi: 10.1016/j.jfluchem.2018.12.004
"Gas-Phase Structures of Protonated Arabino Nucleosides", L. A. Hamlow, C. C. He, Zachary J. Devereaux, H. A. Roy, N. A. Cunningham, E. O. Soley, J. K. Lee, G. Berden, J. Oomens, and M. T. Rodgers, Int. J. Mass Spectrom. 438, 124-134 (2019). Special Issue in Honor of Helmut Schwarz. doi: 10.1016/j.ijms.2019.01.005
"Experimental and Computational Study of the Group 1 Metal Ion Chelates with Lysine: Bond Dissociation Energies, Structures, and Structural Trends", A. A. Clark, B. Yang, M. T. Rodgers, and P. B. Armentrout, J. Phys. Chem. B 123, 1983-1997 (2019). doi: 10.1021/acs.jpcb.8b11967
"Impact of the 2'- and 3'-Sugar Hydroxyl Moieties on Gas-Phase Nucleoside Structure", L. A. Hamlow, Zachary J. Devereaux, H. A. Roy, N. A. Cunningham, J. K. Lee, G. Berden, J. Oomens, and M. T. Rodgers, J. Am. Soc. Mass Spectrom. 441, 32-43 (2019). doi: 10.1016/j.ijms.2019.04.003
"IRMPD Action Spectroscopy, ER-CID Experiments, and Theoretical Approaches Investigate Intrinsic L-Thymidine Properties Compared to D-Thymidine: Findings Support Robust Methodology", E. O. Soley, Zachary J. Devereaux, L. A. Hamlow, G. Berden, J. Oomens, and M. T. Rodgers, Int. J. Mass Spectrom. 441, 32-43 (2019). doi: 10.1016/j.ijms.2019.04.003
"Structures and Relative Glycosidic Bond Stabilities of Protonated 2'-Fluoro Substituted Purine Nucleosides", Zachary J. Devereaux, C. C. He, Y. Zhu, H. A. Roy, N. A. Cunningham, L. A. Hamlow, G. Berden, J. Oomens, and M. T. Rodgers, J. Am. Soc. Mass Spectrom. 30, 1521-1536 (2019). doi: 10.1007/s13361-019-02222-6
"Infrared Multiple Photon Dissociation Action Spectroscopy of Protonated Glycine, Histidine, Lysine, and Arginine Complexes with 18-Crown-6 Ether", C. P. McNary, Y.-w. Nei, Philippe Maitre, M. T. Rodgers, and P. B. Armentrout, Phys. Chem. Chem. Phys. 21, 12625-12639 (2019). doi: 10.1039/C9CP02265A
"Impact of Sodium Cationization on Gas-Phase Conformations of DNA and RNA Cytidine Mononucleotides", L. A. Hamlow, Y.-w. Nei, R. R. Wu, J. Gao, J. D. Steill, G. Berden, J. Oomens, and M. T. Rodgers, J. Am. Soc. Mass Spectrom. 30, 2318-2334 (2019). doi: 10.1007/s13361-019-02300-9
"Structural and Energetic Effects of 2'-Ribose Methylation of Protonated Pyrimidine Nucleosides", C. C. He, L. A. Hamlow, Y. Zhu, Y.-w. Nei, L. Fan, C. P. McNary, P. Maitre, V. Steinmetz, B. Schindler, I. Compagnon, P. B. Armentrout, and M. T. Rodgers, J. Am. Soc. Mass Spectrom. 30, 2318-2334 (2019). doi: 10.1007/s13361-019-02300-9
"Amino Acid-Linked Platinum (II) Compounds: Non-canonical Nucleoside Preferences and Influence on Glycosidic Bond Stabilities", B. Kimutai, C. C. He, A. Roberts, M. L. Jones, X. Bao, J. Jiang, Z. Yang, M. T. Rodgers, and C. S. Chow, J. Biol. Inorg. Chem. 24, 985-997 (2019). doi: 10.1007/s00775-019-01693-7
"Influence of the Local Environment on the Intrinsic Structures of Gas-Phase Cytidine-5' Mononucleotides", L. A. Hamlow, Y.-w. Nei, R. R. Wu, J. Gao, J. D. Steill, G. Berden, J. Oomens, and M. T. Rodgers, Int. J. Mass Spectrom. Epub ahead of print (2019). doi: 10.1016/j.ijms.2019.116234
For a complete list of research publications see http://rodgers.chem.wayne.edu/rodgers/publications.htm