Ph.D. University of Chicago, 1991
High Resolution Microwave Spectroscopy
The research in our group is driven by several related questions: Can we identify and assign the spectral signatures from different conformations of a single molecular species? How do weakly bonding interactions (hydrogen bonding, dipole-dipole, dispersion forces) stabilize some molecular conformations over others? Do interactions with solvent or other neighboring species change the conformational preferences of a molecule? How are the molecular conformations of peptides related to secondary structural motifs of larger peptides and proteins?
Microwave spectroscopy is an excellent tool for addressing these questions. We use two Fourier-transform microwave spectrometers that were custom-constructed in our laboratory. Each spectrometer employs two mirrors for microwave frequencies, and they are positioned to establish a resonant cavity (an integral number of wavelengths between the mirrors). Samples are introduced between the mirrors and irradiated with microwave radiation of some known frequency. If the sample absorbs the radiation, it induces an oscillating signal in an antenna mounted on one of the mirrors. The frequency of the signal is equal to the frequency of the rotational transition; a Fourier-transform converts the oscillating signal into a spectrum as a function of frequency. By measuring rotational transitions, we are able to determine molecular moments of inertia and ultimately determine the bond distances and angles.
Our main area of interest is the study of small biological molecules such as amino acids and peptide derivatives. The conformational structures of individual amino acids in a protein collectively determine the three-dimensional structure of the protein and, ultimately, its biological function. We have investigated the spectroscopy of a number of amino amides (amide derivatives of amino acids) including alaninamide, prolinamide, and valinamide. Sufficient vapor pressure can be obtained for these amides by simply heating the solid samples to ca. 100 - 150 ºC. Our group has also collaborated with colleagues at the National Institute of Standards and Technology to record the first rotationally resolved spectra of a linear dipeptide analogue, N-acetyl alanine methyl amide. Data from the rotational spectra are used to generate the most precise and detailed experimental structures of these species.
Interactions between molecules can be studied using the same technique. We can learn how hydrogen bonds influence the structures of molecular complexes by measuring the lengths of the hydrogen bonds and examining the dynamics of the internal motions. These projects are interesting because hydrogen bonding is a fundamental interaction in biochemistry. Our initial studies of the conformations of alaninamide and alaninamide-water confirmed a decade-old prediction for a similar system that the most stable structure of the complex will be based on the lowest energy monomer conformation. We now seek to identify and characterize molecular complexes in which the formation of intermolecular hydrogen bonds changes the molecular structure away from that of the isolated molecule. We have found, for example, that the O - C - C - N dihedral angle, which defines the conformation of 2-aminoethanol, increases from 58º to 71º upon formation of an intramolecular hydrogen-bonding network in the 2-aminoethanol-water complex. Our recent characterization of a similar hydrogen-bonding network in the glycidol-water complex identified a 9º increase in the glycidol O - C - C - O dihedral angle to accommodate formation of the new intermolecular hydrogen bonds.
Many interesting biological molecules, such as amino acids and peptides, have very low vapor pressures and undergo thermal decomposition upon heating. We have developed a unique laser vaporization sample source to investigate these species. Samples are incorporated into a methyl cellulose matrix, coated onto a sample drum, and placed into the sample source next to the gas expansion channel. Each pulse of carrier gas is accompanied by a 15-mJ pulse of Nd: YAG second harmonic (532 nm) radiation; the focused laser light ablates the sample and matrix into the expansion for the subsequent microwave experiment. The sample drum is rotated and translated so that each laser pulse strikes a fresh region of the sample matrix. We have used our laser vaporization source to measure rotational transitions of 1, 3, 5-trithiane, as well as both low-energy conformations of glycine, and we are now using it to record the rotational spectra of small peptides and other biological molecules.
Scholarly, Creative & Professional Activities
- "A Spectroscopic and Computational Investigation of the Conformational Structural Changes Induced by Hydrogen Bonding Networks in the Glycidol-Water Complex." A. R. Conrad, N. H. Teumelsan, P. E. Wang, and M. J. Tubergen (2010), J. Phys. Chem. A, 114, 336 - 342.
- "Microwave Spectra, r0 Structural Parameters, and Conformational Stability from Xenon Solutions of silylcyclohexane," J. R. Durig, R. M. Ward, A. R. Conrad, M. J. Tubergen, G. A. Giurgis, and T. K. Gounev (2009) J. Mol. Struct., 922, 19 - 29.
- "Gas-Phase Conformational Distributions fro the 2-Alkylalcohols 2-Pentanol and 2-Hexanol from Microwave Spectroscopy." M. J. Tubergen, A. R. Conrad, R. E. Chavez III, I. Hwang, R. D. Suenram, J. J. Pajski, and B. H. Pate (2008) J. Mol. Spectrosc., 251, 330 - 338.
- "Rotational Spectra and Conformational Structures of 1-Phenyl-2-propanol, Methamphetamine, and 1-Phenyl-2-propanone." M. J. Tubergen, R. J. Lavrich, D. F. Plusquellic, and R. D. Suenram (2006) J. Phys. Chem. A, 110, 13188 - 13194.
- "Rotational Spectra, Nuclear Quadrupole Hyperfine Tensors, and Conformational Structures of the Mustard Gas Simulent 2-Chloroethyl Ethyl Sulfide," M. J. Tubergen, A. Lesarri, R. D. Suenram, A. C. Samuels, J. O. Jensen, M. W. Ellzy, and J. M. Lochner (2005) J. Mol. Spectrosc., 233, 180 - 188.
- "Effect of Solvent on Molecular Conformation: Microwave Spectra and Structures of 2-Aminoethanol van der Waals Complexes," M. J. Tubergen, C. R. Torok, and R. J. Lavrich (2003) J. Chem. Phys., 119, 8397 - 8403.
- "Experimental Studies of Peptide Bonds: Identification of the C7eq Conformation of the Alanine Dipeptide Analog N-Acetyl-alanine N'-Methylamide from Torsion-Rotation Interactions," R. J. Lavrich, D. F. Plusquellic, R. D. Suenram, G. T. Fraser, A. R. Hight-Walker, and M. J. Tubergen (2003) J. Chem. Phys., 118, 1253 - 1265.
- "Conformation and Hydrogen Bonding in the Alaninamide-Water van der Waals Complex," R. J. Lavrich and M. J. Tubergen (2000) J. Am. Chem. Soc., 122, 2938 - 2943.