The activity and selectivity of a biologically or pharmacologically relevant molecule are dominated by its molecular shape and conformation. Biomolecular processes in which structure affects function include membrane transport, neurotransmission, drug-receptor interactions, protein-ligand binding, and enzyme catalysis. The overwhelming majority of studies on these molecules are in the condensed phase; solvent effects result in the formation of zwitterions for many of these molecules and thus they lose much conformational freedom. Gas-phase spectroscopy removes solvent and intermolecular interactions resulting in greater conformational freedom and allowing study of neutral species in the isolation required to observe the intrinsic molecular properties of biochemical systems.
Fourier-transform microwave (FTMW) spectroscopy, a rotational spectroscopy technique, is a powerful tool for unambiguous structural characterization of gas-phase biomolecules with results directly comparable to theoretical predictions and can be used to characterize the structural preferences of pertinent biomolecules such as dipeptides and biomolecular complexes such as water complexes of biomolecules. The incredible resolution afforded by FTMW spectroscopy allows for the assignment of rotational spectra arising from different conformers, isotopomers, and tautomers.
This dissertation describes the rotational spectra and structural characterization of a number of biologically relevant molecules. To increase our capabilities to understand the structures of thermally fragile biological species, we have constructed a laser vaporization sample source for a microwave spectrometer. The design and development of a laser vaporization sample source for microwave spectroscopy is described, and the preparation of samples for a number of species for use in the laser vaporization source and resulting rotational spectra are presented.
We utilized FTMW spectroscopy to explore the structures of a number of biologically relevant species including glycidol and the glycidol-water complex, the family of cyanophenol molecules, and leucinamide. The experimental structure of glycidol-water indicates that the glycidol monomer undergoes structural changes to accommodate formation of an intermolecular hydrogen bonding network upon water complexation. One conformer of o-cyanophenol and two conformers of m-cyanophenol were observed spectroscopically. The rotational transitions of p-cyanophenol are split due to the internal rotation of the hydroxyl group with respect to the aromatic ring, and the energy barrier to internal rotation is determined from the spectral splitting. Two isotopomers of two conformers of leucinamide, the amino amide derivative of leucine, were observed, and the gas phase structures are significantly different from the crystal phase structures of leucinamide and the gas phase structures of leucine. The rotational spectra of the monosubstituted cyclohexanes silylcyclohexane, germylcyclohexane, ethynylcyclohexane, and cyanocyclohexane are also reported.