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Dissertation zugänglich unter
Conformational flexibility and complex formation of biologically relevant molecules studied with high-resolution broadband rotational spectroscopy
Untersuchungen zur Konformationsflexibilität und Komplexbildung biologisch relevanter Moleküle mittels hochaufgelöster Breitband-Rotationsspektroskopie
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35.10 , 33.07
Schnell, Melanie (Dr.)
Tag der mündlichen Prüfung:
Kurzfassung auf Englisch:
The motivation to understand intermolecular interactions on a fundamental level encourages natural scientists for more than 120 years. In 1894, Emil Fischer developed the key-lock principle to describe the binding process between an enzyme and a corresponding substrate. As simple and understandable this picture is in general, as complicated and complex is the understanding of it on a molecular level.
Countless examples exist that demonstrate the importance of this key-lock principle, from the interaction between neurotransmitter and receptor or the antigen recognition to the interaction of carbohydrates on the cell surface. All of these examples have in common that large biomolecular systems are involved, built up by long chains of amino acids, monosaccharides or nucleotides. The folding of these chains into a three-dimensional structure, for example in enzymes, often reveals an active site, where the interaction takes place. At the active site only a few molecules might be involved in the so called molecular recognition process. In this work, model systems of biologically relevant molecules and complexes are studied, modeling the active side of a biological system.
For a fundamental understanding of recognition processes in nature it is important to study the interplay between different intermolecular forces, like hydrogen bonding or dispersion interaction. Additionally, it is also essential to gain information about the conformational flexibility of the molecule itself, which allows for structural changes during the recognition process. This can be referred to the induced t picture, an extension of the key-lock principle, postulated by Daniel E. Koshland in 1958, whereby the substrate induces a structural change in the enzyme upon binding, to fit into the active site.
High-resolution microwave spectroscopy is perfectly suited to study conformational flexibility and intermolecular interactions of biologically relevant molecules. The exceptional accuracy of the obtained spectroscopic constants allows for precise structure determination of gas-phase molecules from only the experimental data. Furthermore, even subtle changes of the structure can be identified in the rotational spectrum, since the spectrum is like a fingerprint of the molecule. The recently developed broadband technique, used in this study, allows for measuring a broad part of the microwave spectrum in a very time efficient way. Different conformers, isomers or complexes can all be studied in one spectrum.
In the framework of this thesis a broadband microwave spectrometer with an implemented laser ablation source was built up and put into operation. A precise structure determination was achieved for the odorant molecule cinnamaldehyde, which is the main component of cinnamon oil. Furthermore, the widespread drug ibuprofen was studied, which is a highly flexible molecule. Interesting insight into the structural properties, like the preferred orientation of the substitutions of its aromatic ring, could be obtained.
Additionally, the interplay of different intermolecular forces was studied on two different complexes. The aggregation of the small sugar glycolaldehyde and the interaction in the diphenylether methanol complex gave information about the competition and cooperativity of hydrogen bonding and dispersion interactions. The second complex is the start of a series of studies of similar complex systems with an increasing size of the alcohol, where it is expected that the dominance of dispersion will be increase.