From Microwave, Infrared to UV: Probing the Conformational Preferences for Biomolecules with Intramolecular Hydrogen Bonds

Di Zhang, Purdue University

Abstract

Hydrogen bonds play very important roles in the structural organizations of biological molecules. The best way to study hydrogen bonded molecules in the gas phase is through optical spectroscopic methods in the microwave, infrared and UV range coupled with supersonic jet expansion. This dissertation characterizes the potential energy surfaces of several biological molecules with intramolecular hydrogen bonds through a combination of different spectroscopic and theoretical methods. The single conformation spectroscopy of suberoylanilide hydroxamic acid (SAHA) is presented first. SAHA is a histone deacetylase inhibitor and anti-cancer drug. Its structure is very unique with a formanilide “head” and a hydroxamic acid “tail” separated by a n-hexyl chain. As a result, the alkyl chain’s preference for extended structures is in competition with tail to-head (T-H) or head-to-tail (H-T) hydrogen bonds between the amide and hydroxamic acid groups. Three conformers of SAHA were distinguished and spectroscopically characterized. A modified version of the generalized Amber force field was used to generate a disconnectivity diagram for the low-energy portion of the potential energy landscape of SAHA. This combination of force field and DFT calculations provides insight into the potential energy landscape and how population was funneled into the three observed conformers. For small molecules without a chromophore, their intramolecular hydrogen bond patterns were studied through broadband microwave spectroscopy. The rotational spectra of D-threoninol, D-allo-threoninol, 2-amino-1,3-propanediol, 1,3-diamino-2-propanol and propane-1,2,3-triamine have been recorded under jet cooled conditions through chirped-pulse Fourier transform microwave spectroscopy. In total, 22 conformers were assigned in the expansion for those 5 small amino alcohol molecules. With three adjacent H-bonding substitutes along the alkyl chain, both hydrogen-bonded cycles (3 H-bonds) and hydrogen-bonded chains (2 H-bonds) were observed. Both families remain close in energy. In D-threoninol, D-allo-threoninol, 2-amino-1,3-propanediol and 1,3-diamino-2- propanol, H-bonded cycles are most highly populated while curved and extended chain structures are favored by propane-1,2,3-triamine. Finally, a room temperature detection method employing chirped-pulse Fourier transform microwave spectroscopy coupled with a waveguide and an ultrafast digitizer is described. The ultrafast speed of the digitizer enables up to 1 billion shots averages of the sample molecule. In the collected room temperature spectra of isobutanol, 4 conformers were observed and assigned. Aside from transitions from ground state, a large number of transitions from vibrationally excited states were also observed and predicted through theoretical methods.

Degree

Ph.D.

Advisors

Zwier, Purdue University.

Subject Area

Physical chemistry

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