Assessing the Functional Structure of Molecular Transporters by EPR Spectroscopy

Amphiphilicity is a key structure forming element in many biological and synthetic systems. In the most general definition, it describes any chemical or structural contrast within a molecule, such as polar/non-polar, hydrocarbon/fluorocarbon, oligosiloxane/hydrocarbon or rigid/flexible. In this thesis, the amphiphilicity in its original definition is studied, namely the chimeric affinity of molecules for water due to hydrophilic and hydrophobic groups. In particular, amphiphiles have a tendency to self-assemble into larger structures due to partly non-favorable interactions with a solvent.

In 1921, Gerlach and Stern observed that a beam of silver atoms splits into two lines when it is subjected to a magnetic field. While the line splitting in optical spectra, first found by Zeeman in 1896, could be explained by the angular momentum of the electrons, the s-electron of silver could not be subject to such a momentum, not to mention that an azimuthal quantum number l = 1/2 cannot be explained by classical physics. At that time, quantum mechanics was still an emerging field in physics and it took another three years until this anormal Zeeman effect was correctly interpreted by the joint research of Uhlenbeck, a classical physicist, and Goudsmit, a fellow of Paul Ehrenfest. They postulated a so-called ‘spin’, a quantized angular momentum, as an intrinsic property of the electron. This research marks the cornerstone of electron paramagnetic resonance (EPR) spectroscopy which is based on the transitions between quantized states of the resulting magnetic moment.

Human serum albumin (HSA) is a versatile transport protein for various endogenous compounds and drugs. This study focuses on its highly relevant transport function for fatty acids in the circulatory system. While extensive crystallographic data on HSA–fatty acid binding exist, a new spectroscopic approach is used to gain information on the functional structure of HSA in solution. Using spin-labeled stearic acid and applying double electron–electron resonance (DEER) spectroscopy, the functional protein structure is accessed for the first time from the ligands’ point of view.

Oligomers based on cholic acid are known to form hydrophobic cavities in hydrophilic solvents due to the facial amphiphilicity of their building blocks. In such pockets, non-polar molecules such as pyrene can be hosted. Oligomers with 1,2,3-triazole moieties are also able to coordinate heavy metal ions. Depending on their position in the cholic acid oligomer, the triazole groups may either cooperatively bind to the metal ion in analogy to a tridentate ligand or act as single entities.

The thermal transition of thermoresponsive dendronized polymers is characterized on a molecular scale by continuous wave EPR spectroscopy. It is found to be accompanied by dynamic structural heterogeneities on the nanoscale, which trigger the aggregation of single polymer chains into mesoglobules. While macroscopically a sharp phase transition, this study reveals that the dehydration of the polymer chains proceeds over a temperature interval of at least 30 K and is a case of a molecularly controlled non-equilibrium state. While the aggregation temperature mainly depends on the periphery of the dendrons, the dehydration of the mesoglobule is governed by the hydrophobicity of the dendritic core. Heating rate dependent changes were assigned to the formation of a dense polymeric layer at the periphery of the mesoglobule, which prohibits the release of incorporated water.