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Our research is focused on understanding the role of weakly bonding interactions in determining the conformational structures of large molecules and molecular complexes. Hydrogen bonding, dipole-dipole, and dispersion forces have long been known to determine the structures of molecular complexes formed in the ultracold environment of supersonic expansions; these same forces also preferentially stabilize some molecular conformations over others.

Microwave spectroscopy is an excellent tool for examining these weak interactions. We use a Fourier-transform microwave spectrometer that was recently constructed in our laboratory. Sample is admitted into the spectrometer by a supersonic expansion of argon which both cools the molecules to ~5 K (rotational temperature) and isolates molecules from neighbors—eliminating the possibility that interactions between molecules might distort the conformational structure. Molecular complexes may also be formed in the expansion by entraining two different sample molecules into the carrier gas.

The spectrometer employs two mirrors for microwave frequencies, and they are positioned to establish a resonant cavity (an integral number of wavelengths between the mirrors). The sample is 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 the opposite mirror. 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.

One area of application 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 recently investigated the spectroscopy of a number of amino amides (amide derivatives of amino acids) including alaninamide, prolinamide, and valinamide. We have 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 of these species are used to generate the most precise and detailed experimental structures.

Interactions between molecules can be studied using the same technique. We have been interested in 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. But we would like to extend our previous studies to consider how the formation of an intermolecular hydrogen bond in a molecular complex affects the relative stability of different conformers. Our recent studies of the conformations of alaninamide and alaninamide-water have 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. Recently we have shown that formation of the 1:1 complex 2-aminoethanol-water changes the conformational structure of 2-aminoethanol. The 2-aminoethanol O–C–C–N dihedral angle increases from 58° to 71° upon formation of an intermolecular hydrogen bond.

These studies provide an important link between molecular modeling, which predicts conformational structures of isolated molecules, and biochemistry, which is concerned with structures in solvent environments. Because computer modeling of molecular structures has become widespread in the design of new polymers and drugs, these projects are particularly relevant.

Selected Publications

1. Tubergen, M. J. et al. Rotational spectra, nuclear quadrupole hyperfine tensors, and conformational structures of the mustard gas simulent 2-chloroethyl ethyl sulfide. Journal of Molecular Spectroscopy 233, 180-188 (2005).