Aggregation of the Amyloid β (Aβ) peptide to amyloid fibrils is associated with the outbreak of Alzheimer’s disease. Early aggregation intermediates in form of soluble oligomers are of special interest as they are believed to be the major toxic components in the process. These oligomers are of disordered and transient nature. Therefore, their detailed molecular structure is difficult to access experimentally and often remains unknown. In the present work extensive, fully atomistic replica exchange molecular dynamics simulations were performed to study the preaggregated, monomer states and early aggregation intermediates (dimers, trimers) of Aβ(25-35) and Aβ(10-35)-NH2 in aqueous solution. The folding and aggregation of Aβ(25-35) were studied at neutral pH and 293 K. Aβ(25-35) monomers mainly adopt β-hairpin conformations characterized by a β-turn formed by residues G29 and A30, and a β-sheet between residues N27–K28 and I31–I32 in equilibrium with coiled conformations. The β-hairpin conformations served as initial configurations to model spontaneous aggregation of Aβ(25-35). As expected, within the Aβ(25-35) dimer and trimer ensembles many different poorly populated conformations appear. Nevertheless, we were able to distinguish between disordered and fibril-like oligomers. Whereas disordered oligomers are rather compact with few intermolecular hydrogen bonds (HBs), fibril-like oligomers are characterized by the formation of large intermolecular β-sheets. In most of the fibril-like dimers and trimers individual peptides are fully extended forming in- or out-of-register antiparallel β-sheets. A small amount of fibril-like trimers contained V-shaped peptides forming parallel β-sheets. The dimensions of extended and V-shaped oligomers correspond well to the diameters of two distinct morphologies found for Aβ(25-35) fibrils. The transition from disordered to fibril-like Aβ(25-35) dimers is unfavorable but driven by energy. The lower energy of fibril-like dimers arises from favorable intermolecular HBs and other electrostatic interactions which compete with a loss in entropy. Approximately 25 % of the entropic cost correspond to configurational entropy. The rest relates to solvent entropy, presumably caused by hydrophobic and electrostatic effects. In contrast to the transition towards fibril-like dimers the first step of aggregation is driven by entropy. Here, we compared structural and thermodynamic properties of the individual monomer, dimer and trimer ensembles to gain qualitative information about the aggregation process. The β-hairpin conformation observed for monomers is successively dissolved in dimer and trimer ensembles while instead intermolecular β-sheets are formed. As expected upon aggregation the configurational entropy decreases. Additionally, the solvent accessible surface area (SASA), especially the hydrophobic SASA, decreases yielding a favorable solvation free energy which overcompensates the loss in configurational entropy. In summary, the hydrophobic effect, possibly combined with electrostatic effects, yields an increase in solvent entropy which is believed to be one major driving force towards aggregation. Spontaneous folding of the Aβ(10-35)-NH2 monomer was modeled using two force fields, GROMOS96 43a1 and OPLS/AA, and compared to primary NMR data collected at pH 5.6 and 283 K taken from the literature. Unexpectedly, the two force fields yielded significantly different main conformations. Comparison between experimental and calculated nuclear Overhauser effect (NOE) distances is not sufficient to distinguish between the different force fields. Additionally, the comparison with scalar coupling constants suggest that the chosen protonation in both simulations corresponds to a pH lower than in the experiment. Based on this analysis we were unable to determine which force field yields a better description of this system. Dimerization of Aβ(10-35)-NH2 was studied at neutral pH and 300 K. Dimer conformations arrange in many distinct, poorly populated and rather complex alignments or interlocking patterns which are rather stabilized by side chain interactions than by specific intermolecular hydrogen bonds. Similar to Aβ(25-35) dimers, transition towards β-sheet-rich, fibril-like Aβ(10-35) dimers is driven by energy competing with a loss in entropy. Here, transition is mediated by favorable peptide-solvent and solvent-solvent interactions mainly arising from electrostatic interactions. / Die Aggregation des Amyloid β (Aβ) Peptids zu Amyloidfibrillen wird mit dem Ausbruch der Alzheimer Krankheit in Verbindung gebracht. Die toxische Wirkung auf Zellen wird vor allem den zeitigen Intermediaten in Form von löslichen Oligomeren zugeschrieben. Aufgrund deren ungeordneter und flüchtiger Natur kann die molekulare Struktur solcher zeitigen Oligomere oft experimentell nicht aufgelöst werden. In der vorliegenden Arbeit wurden aufwendige atomistische Replica-Exchange-Molekulardynamik-Simulationen durchgeführt, um die molekulare Struktur von Monomeren und Oligomeren der Fragmente Aβ(25-35) und Aβ(10-35)-NH2 in Wasser zu untersuchen. Die Faltung und Aggregation von Aβ(25-35) wurde bei neutralem pH und 293 K untersucht. Monomere dieses Fragments bilden hauptsächlich β-Haarnadelkonformationen im Gleichgewicht mit Knäulstrukturen. Innerhalb der β-Haarnadelkonformationen bilden die Residuen G29 und A30 einen β-turn, während N27–K28 and I31–I32 ein β-Faltblatt bilden. Diese β-Haarnadelkonformationen bildeten den Ausgangspunkt zur Modellierung spontaner Aggregation. Wie zu erwarten, bilden sich eine Vielzahl verschiedener, gering besetzter Dimer- und Trimerkonformationen. Mit Hilfe einer gröberen Einteilung können diese in ungeordnete und fibrillähnliche Oligomere unterteilt werden. Ungeordnete Oligomere bilden kompakte Strukturen, die nur durch wenige intermolekulare Wasserstoffbrückenbindungen (HBB) stabilisiert sind. Typisch für fibrillähnliche Oligomere ist hingegen die Ausbildung großer intermolekularer β-Faltblätter. In vielen dieser Oligomere finden wir antiparallele, in- oder out-of-register β-Faltblätter gebildet durch vollständig ausgestreckte Peptide. Ein kleiner Teil der fibrillähnlichen Trimere bildet parallele, V-förmige β-Faltblätter. Die Ausdehnungen ausgestreckter und V-förmiger Oligomere entspricht in etwa den Durchmessern von zwei verschiedenen, experimentell gefundenen Fibrillmorphologien für Aβ(25-35). Die Umwandlung von ungeordneten zu fibrillähnlichen Aβ(25-35) Dimeren ist energetisch begünstigt, läuft aber nicht freiwillig ab. Fibrillähnliche Dimere haben eine geringere Energie aufgrund günstiger Peptidwechselwirkungen (HBB, Salzbrücken), welche durch den Verlust an Entropie kompensiert wird. Etwa 25 % entsprechen dem Verlust an Konfigurationsentropie. Der restliche Anteil wird einem Verlust an Lösungsmittelentropie aufgrund von hydrophoben und elektrostatischen Effekten zugesprochen. Im Gegensatz zur Umwandlung in fibrillähnliche Dimere, ist die Assoziation von Monomeren oder Oligomeren entropisch begünstigt. Beim Vergleich thermodynamischer Eigenschaften der Monomer-, Dimer- und Trimersysteme zeigt sich im Verlauf der Aggregation, wie erwartet, eine Abnahme der Konfigurationsentropie. Zusätzlich nimmt die dem Lösungsmittel zugängliche Oberfläche (SASA), insbesondere die hydrophobe SASA, ab. In Verbindung damit beobachten wir eine Abnahme der freien Solvatisierungsenergie, welche den Verlust an Konfigurationsentropie kompensiert. Mit anderen Worten, der hydrophobe Effekt in Kombination mit elektrostatischen Wechselwirkungen führt zu einem Ansteigen der Lösungsmittelentropie und begünstigt damit die Aggegation. Die spontane Faltung des Aβ(10-35)-NH2 Monomers wurde für zwei verschiedene Proteinkraftfelder, GROMOS96 43a1 und OPLS/AA, untersucht und mit primären NMR-Daten aus der Literatur, gemessen bei pH 5.6 und 283 K, verglichen. Beide Kraftfelder generieren unterschiedliche Hauptkonformationen. Der Vergleich zwischen experimentellen und berechneten Kern-Overhauser-Effekt (NOE) Abständen ist nicht ausreichend, um zwischen beiden Kraftfeldern zu unterscheiden. Der Vergleich mit Kopplungskonstanten aus Experiment und Simulation zeigt, dass beide Simulationen einem pH-Wert geringer als 5.6 ensprechen. Basierend auf den bisherigen Ergebnissen können wir nicht entscheiden, welches Kraftfeld eine bessere Beschreibung für dieses System liefert. Die Dimerisierung von Aβ(10-35)-NH2 wurde bei neutralem pH und 300 K untersucht. Wir finden eine Vielzahl verschiedener, gering besetzter Dimerstrukturen, welche eher durch Seitenkettenkontakte als durch spezifische HBB stabilisiert sind. Wie bei den Aβ(25-35) Dimeren, ist die Umwandlung zu β-Faltblattreichen, fibrillähnlichen Aβ(10-35) Dimeren energetisch begünstigt, konkurriert aber mit einem Entropieverlust. Die Umwandlung wird in diesem Fall durch elektrostatische Wechselwirkungen zwischen Peptid und Lösungsmittel und innerhalb des Lösungsmittels bestimmt.

An extension of the nonadiabatic quantum molecular dynamics approach is presented to account for electron-nuclear correlations in the dynamics of atomic many-body systems. The method combines electron dynamics described within time-dependent density-functional or Hartree-Fock theory with trajectory-surface-hopping dynamics for the nuclei, allowing us to take into account explicitly a possible external laser field. As a case study, a model system of H++H collisions is considered where full quantum-mechanical calculations are available for comparison. For this benchmark system the extended surface-hopping scheme exactly reproduces the full quantum results. Future applications are briefly outlined.

An extension of the nonadiabatic quantum molecular dynamics approach is presented to account for electron-nuclear correlations in the dynamics of atomic many-body systems. The method combines electron dynamics described within time-dependent density-functional or Hartree-Fock theory with trajectory-surface-hopping dynamics for the nuclei, allowing us to take into account explicitly a possible external laser field. As a case study, a model system of H++H collisions is considered where full quantum-mechanical calculations are available for comparison. For this benchmark system the extended surface-hopping scheme exactly reproduces the full quantum results. Future applications are briefly outlined.

Diese Arbeit charakterisiert die Solvatation des organischen Farbstoffes Coumarin 153 in Gemischen aus jeweils einem Alkan und einem Alkohol. Dabei werden Methoden der statischen und zeitaufgeloesten optischen Spektroskopie sowie klassische molekulardynamische Simulationen fuer die Untersuchungen angewendet. Die experimentellen Ergebnisse zeigen, dass der Farbstoff im Gemisch selektiv durch den Alkohol solvatisiert ist. Die Staerke dieser Solvatation ist für den elektronischen Grund- und Anregungszustand des Farbstoffes unterschiedlich. Aus diesem Grund wird die Solvatationsdynamik in Alkohol/Alkan Gemischen durch einen Translationsdiffusionsprozess bestimmt. Die molekulardynamischen Simulationen veranschaulichen die selektive Solvatation des Coumarin 153 in einem Methanol/Hexan Gemisch. Die Solvathuelle enhaelt im Anregungszustand des Farbstoffes bis zu dreimal mehr Molekuele als im Grundzustand. Im Unterschied zur Solvatation in reinem Methanol spielen spezifische Bindungen wie Wasserstoffbrueckenbindungen in einem Methanol/Hexan Gemisch eine wesentliche Rolle.

Glycosaminoglycans (GAGs) are linear polysaccharides, built of periodically occurring disaccharide units. GAGs are ubiquitous in the extracellular matrix (ECM), where they exhibit multifarious biological activities. This diversity arises from - among others - their ability to interact with and regulate a large number of proteins, such as cytokines, chemokines, and growth factors. As of the huge variety in their chemical configuration, GAGs are further sub-classified into different types (heparin, for instance, is one of these sub-classes). Hence, GAGs are a diverse class of molecules, which surely contributes to the broadness of their spectrum of biological functions. Through varying arrangements of sulfate groups and different types of saccharide units, individual GAG molecules can establish specific atomic contacts to proteins. One of the best-studied examples is antithrombin-heparin, whose biologically relevant interaction requires a specific pentasaccharide sequence. It is valid to assume, however, that various proteins are yet to be discovered whose biological functions are in some way affected by GAGs. In other cases, and this is true for the cytokine interleukin-10 (IL-10), there are already experimental indications for a biologically relevant protein-GAG interaction, but the details are still obscure and the fundamental molecular interaction mechanism has still not been clarified. IL-10 has been shown to bind GAGs. So far, however, no structural detail about IL-10-GAG interaction is known. Function-wise, IL-10 is mainly considered to be immunosuppressive and therefore anti-inflammatory, but it in fact has the pleiotropic ability to influence the immune system in both directions, i.e. it constitutes a complex regulation system on its own. Therefore, the role of GAGs in this system is potentially substantial, but is yet to be clarified. In vitro experiments have yielded indications for GAGs being able to modulate IL-10\'s biological function, and obviously IL-10 and GAGs are simultaneously present in the ECM. This gives rise to the assumption that IL-10-GAG interaction is of biological significance, and that understanding the impact of GAGs on IL-10 biology is important - from the basic research point of view, but also for the development of therapies, potentially involving artificially designed ECMs. A promising approach for obtaining knowledge about the nature of IL-10-GAG interaction is its investigation on the structural level, i.e. the identification and characterization of the molecular interaction mechanisms that govern the IL-10-GAG system. In this PhD project it was my goal to reveal structural and molecular details about IL-10-GAG interaction with theoretical and computational means, and with the help of experiments performed by collaborators in the framework of the Collaborative Research Centre DFG Transregio 67. For achieving this, I developed three methods for the in silico investigation of protein-GAG systems in general and subsequently applied them to the IL-10-GAG system. Parts of that work have been published in scientific journals, as outlined further below. I proposed and validated a systematic approach for predicting GAG binding regions on a given protein, based on the numerical simulation and analysis of its Coulomb potential. One advantage of this method is its intrinsic ability to provide clues about the reliability of the resulting prediction. Application of this approach to IL-10 lead to the observation that its Coulomb attraction for GAGs is significantly weaker than in case of exemplary protein-GAG systems (such as FGF2-heparin). Still, a distinct IL-10-GAG binding region centered on the residues R102, R104, R106, R107 of the human IL-10 sequence was identified. This region can be assumed to play a major role in IL-10-GAG interaction, as described in chapter 3. Molecular docking methods are used to generate binding mode predictions for a given receptor-ligand system. In chapter 4, I clarify the importance of data clustering as an essential step for post-processing docking results and present a clustering methodology optimized for GAG molecules. It allows for a reproducible analysis, enabling systematic comparisons among different docking studies. The approach has become standard procedure in our research group. It has been applied in a variety of studies, and served as an essential tool for studying IL-10-GAG interaction, as described in chapter 3. Motivated by the shortcomings of classical docking approaches, especially with respect to protein-GAG systems, I worked on the development of a molecular dynamics-based docking method with less radical approximations than usually applied in classical docking. The goal was to make the computational model properly account for the special physical properties of GAGs, and to include the effects of receptor flexibility and solvation. The methodology was named Dynamic Molecular Docking (DMD) and published in the Journal of Chemical Information and Modeling-together with a validation study. The subsequent application of DMD in a variety of studies required enormous amounts of computational resources. For tackling this challenge, I established a graphics processing unit-based high-performance computing environment in our research group and developed a software framework for reliably performing DMD studies on this hardware, as well as on other computing resources of the TU Dresden. The investigation of the IL-10-GAG system via DMD was focused on the IL-10-GAG binding region predicted earlier, and made heavy usage of the optimized clustering approach named above. An important result of this endeavor is that IL-10's amino acid residue R107 significantly stands out compared to all other residues and supposedly plays a particularly important role in IL-10-GAG recognition. The collaboration with the NMR laboratory of Prof. Daniel Huster at the Universität Leipzig was fruitful: I post-processed nuclear Overhauser effect data and obtained heparin structure models, which revealed that IL-10-heparin interaction has a measurable impact on the backbone structure of the heparin molecule. These results were published in Glycobiology. In chapter 8, I propose two different scenarios about how GAG-binding to IL-10 might affect its biological function, based on the findings made in this thesis project. In conclusion, a set of methods has been developed, all of which are generically applicable for the investigation of protein-GAG systems. Regarding the IL-10-GAG system, valuable structural insights for increasing the understanding about its molecular mechanisms were derived. These observations pave the way towards unraveling GAG-mediated bioactivity of IL-10, which may then be specifically exploited, for instance in artificial ECMs for improved wound healing.

An extension of the nonadiabatic quantum molecular dynamics approach is presented to account for electron-nuclear correlations in the dynamics of atomic many-body systems. The method combines electron dynamics described within time-dependent density-functional or Hartree-Fock theory with trajectory-surface-hopping dynamics for the nuclei, allowing us to take into account explicitly a possible external laser field. As a case study, a model system of H++H collisions is considered where full quantum-mechanical calculations are available for comparison. For this benchmark system the extended surface-hopping scheme exactly reproduces the full quantum results. Future applications are briefly outlined.

Molekulardynamik (MD) Simulationen wurden an zwei verschiedenen Systemen durchgeführt: 1. Grenzfläche zwischen Polyethylen und isotaktischem Polypropylen (PE-iPP) und 2. Zylindrische Mizellen, bestehend aus Tetradecyltrimethylammoniumbromid (C14TAB), in wässriger Lösung und an Fest-Flüssig-Grenzflächen. Die allgemeinen Schwierigkeiten bei der Simulation von Grenzflächen kristalliner Polymere wurden diskutiert und eine Methode für solche Simulationen vorgeschlagen. Diese Methode wurde zur epitaxialen Kristallisation von PE auf iPP benutzt. Experimentelle Ergebnisse der epitaxialen Kristallisation konnten durch die Simulation bestätigt werden. Ferner konnte vorhergesagt werden, dass PE bevorzugt auf einer iPP-Oberfläche mit hoher Methylgruppenkonzentration kristallisiert. Ebenso wurde durch die MD Simulation vorhergesagt, dass PE in der Grenzflächenregion von einer orthorhombischen zur monoklinischen Kristallstruktur wechselt. Die Simulationsdauer für die Mizellen betrug einige Nanosekunden. Die Ergebnisse für die Mizellen in wässriger Lösung stehen hierbei in guter Übereinstimmung mit experimentellen Werten. Im Widerspruch zur allgemein üblichen Vorstellung führte die Simulation der Mizellen zur Ausbildung eines Hohlraums in ihrer Mitte sowie zu einer inhomogenen Dichte des hydrophoben Mizellkerns. Dies wurde zum Teil der inhomogenen Verteilung der terminalen Methylgruppen im Mizellkern zugeschrieben. Zylindrische und halbzylindrische Mizellen wurden an den Paraffin/Wasser- und Gold/Wasser-Grenzflächen simuliert. / Molecular Dynamic (MD) simulation of two different systems was performed: 1) Polyethylene- isotactic Polypropylene (PE-iPP) interfaces and 2) cylindrical micelles formed by tetradecyl trimethylammonium bromide (C14TAB) molecules in aqueous solution and at solid liquid interfaces. The general difficulties of simulation of polymer crystalline interfaces were discussed and one method was proposed for such simulations. Thise method was used to simulate epitaxial crystallisation of PE on iPP. The experimental results on epitaxial crystallisation were confirmed by MD simulation and in addition epitaxial crystallisation of PE on iPP surface with high dencity of methyl groups was predicted. MD simulation also predicted that PE should change at the interfacial region from the orthorhombic to monoclinic crystalline structure. Several nanoseconds of life of cylindrical micelles were simulated. The simulation results for the micelle in aqueous solution were favourably compared with experimental results. In contradiction to the standard picture of an ionic micelle the simulated micelle formed hole in its centre and the density of the hydrophobic micelle core was inhomogeneous. This effect partially was explained by the inhomogeneous distribution of the terminal methyl groups in the micelle core. Cylindrical and half cylindrical micelles of C14TAB molecules were simulated at the paraffin- and gold-aqueous interfaces.

Die optoelektronischen Eigenschaften von inorganischen/organischen Hybridmaterialien (HIOS) sind besonders von der Kristallstruktur und der Ausrichtung der organischen Moleküle relativ zur inorganischen Oberfläche abhängig. Beides hängt von den kollektiven Wechselwirkungen der Materialien und von Transportprozessen wie etwa der Diffusion während der Deposition der organischen Materialien auf inorganischen Oberflächen ab. Durch die Komplexität solcher System sind jedoch viele Fragen im Bezug auf die gezielte Herstellung und Vorhersage von HIOS-Strukturen offen. Die Ziele dieser Arbeit sind daher (1) die theoretische Reproduktion der experimentell bekannten Einkristall-Struktur des weit verbreiteten organischen Moleküls para-Sexiphenyl (p-6P) und (2) die Untersuchung der Selbstdiffusion eines einzelnen p-6P auf einer inorganischen Zinkoxid (ZnO) Oberfläche. Die jeweiligen Systeme werden mittels klassischer atomistischer Molekulardynamik Simulationen und mit Methoden der klassischen Diffusionstheorie untersucht. Die Arbeit demonstriert, dass ein Modell basierend auf einem klassischen Kraftfeld die internen geometrischen und energetischen Eigenschaften eines realen p-6P Moleküls reproduziert. Wir simulieren die Selbstanordnung von p-6P zu Kristallen mit der experimentellen Einkristall-Struktur des p-6P und reproduzieren das reale Phasenverhalten des p-6P Kristalls. Wir untersuchen den Zusammenhang zwischen der Oberflächendiffusion eines p-6P und der elektrostatischen Kopplung zur ZnO (10-10)-Oberfläche. Wir entwickeln Strategien zur Berechnung von freie-Energie Landschaften, Diffusionskoeffizienten und Übergangsraten über Stufenkanten. Im Ergebnis hängen die Übergangsraten exponentiell von der Temperatur, der elektrostatischen Kopplung und der Höhe der Stufenkanten ab. Wir entdecken zudem zwei unterschiedliche Übergangspfade des p-6P über Stufenkanten, die von der Temperatur des Systems und von der elektrostatischen Kopplung abhängen. / The optoelectronic properties of hybrid inorganic/organic semiconductors strongly depend on the crystal structure and alignment of the molecules relative to the surface. Structure and alignment, in turn, depend on the surface-molecule and molecule-molecule interactions as well as transport processes such as diffusion during deposition of the organic molecules on an inorganic surface. However, due to their high complexity, fundamental questions pertaining to the design and prediction of HIOS structure are still unanswered. The aims of this thesis are therefore (1) to theoretically reproduce experimental bulk crystal structures of the widely used organic para-sexiphenyl molecule (p-6P) and (2) to investigate the self-diffusion of a single p-6P deposited on an inorganic Zincoxide (ZnO) surface. A multi-scale strategy is used, combining quantum density functional theory (DFT), all-atom molecular dynamics simulations, and classical diffusion theory. The thesis demonstrates that a classical force field model yields self-assembled bulk crystal structures and reproduces the real solid to liquid crystal phase behavior. The internal geometries and energies of the p-6P molecule and the structure of the p-6P bulk crystal are reproduced, all consistent with DFT and experiments. We investigate how the diffusion of the p-6P relates to the surface structure and the electrostatic coupling between the molecule and the ZnO (10-10) surface. We investigate by means of an advanced sampling strategy, free energy landscapes, diffusion coefficients and crossing rates over surface-step-edges. We find that the reciprocal values of the rates depend exponentially on the system temperature, the amplitude of the surface charges and the step-edge height, as well as linearly on the distance between equally high steps. We also discover two different crossing pathways for the molecule moving over the step, which simultaneously depend on the system temperature and the electrostatic coupling.

Elektronische, optische und kollektive Vielteilcheneigenschaften molekularer Systeme in polaren Umgebungen werden durch elektrische Wechselwirkungen, die bei Terahertz-Frequenzen (THz) fluktuieren, beeinflusst. Diese Arbeit nutzt die Fortschritte bei Hochfeld-THz-Quellen, um Einblicke in die lokalen Wechselwirkungen und die Dynamik elektrischer Felder auf relevanten Zeitskalen bei Umgebungstemperaturen zu gewinnen. Die Forschung wird von drei miteinander verbundenen Zielen geleitet: (1) Die optische Gleichrichtung mit gekippten Pulsfronten in LiNbO3 erzeugt starke Pikosekunden-THz-Pulse, die bei 0,6 THz zentriert sind und durch eine metallische Antennenstruktur verstärkt werden, um elektrische Spitzenfelder bis zu 3 MV/cm zu erreichen. (2) Wir stellen eine neue Methode der THz-Stark-Spektroskopie vor. Die Experimente basieren auf einem Pump-Probe-Schema, bei dem starke elektrische Felder von THz-Pulsen nicht-resonant mit einem Chromophor wechselwirken und Änderungen der molekularen elektronischen Absorptionsbanden hervorrufen. Die Änderungen werden dann frequenz- und zeitaufgelöst mit optischen Femtosekunden-Pulsen abgebildet. Die Zeitskala der THz-Pulse ist viel kürzer als die molekularen Umorientierungsprozesse, so dass die Experimente die quasi-instante Reaktion molekularer Systeme in einer eingefrorenen Strukturanordnung abbilden. Aus den vollständig reversiblen elektronischen Absorptionsänderungen kann man eine Dipoldifferenz zwischen dem Grund- und dem angeregten Zustand und Einblicke in die lokale elektrische Umgebung gewinnen. (3) Nach Photoanregung freier Elektronen in polaren Flüssigkeiten führt die ultraschnelle Relaxation der Elektronen zu stark unterdämpften kohärenten Ladungsschwingungen mit Frequenzen zwischen 0,1-2 THz. Solche Anregungen stellen longitudinale Polaronen dar, bei denen ein überschüssiges Elektron an Zehntausende von Lösungsmittelmolekülen gekoppelt ist und ein Polaron von Nanometergröße bildet. / The behavior of molecular systems in polar environments is influenced by electric interactions fluctuating at terahertz (THz) frequencies, shaping their electronic, optical, and collective many-body properties. This thesis leverages the advancements in high-field THz sources to gain insights into the local electric-field interactions and dynamics at relevant timescales under ambient temperatures. The research is guided by three interconnected objectives: (1) Tilted-pulse-front optical rectification in LiNbO3 generates strong picosecond THz pulses centered at 0.6 THz which are enhanced by a metallic antenna structure to reach peak electric fields up to 3 MV/cm. (2) We introduce a novel method of THz Stark spectroscopy. The experiments are based on a pump-probe scheme, where strong electric fields of THz pulses interact non-resonantly with a chromophore and induce changes of molecular electronic absorption bands. The changes are then mapped in a frequency- and time-resolved manner using femtosecond optical probe pulses. The time-scale of the THz pulses is much shorter than the molecular reorientation processes, thus, the experiments map the quasi-instantaneous response of molecular systems in a frozen structural arrangement. From the fully reversible electronic absorption changes, one can obtain a dipole difference between the ground and the excited state, and insights into the local electric environment. (3) Following photoexcitation of free electron in polar liquids, the ultrafast relaxation of electrons leads to highly underdamped coherent charge oscillations at frequencies between 0.1-2 THz. Such excitations represent longitudinal polarons, where an excess electron is coupled to tens of thousands of solvent molecules forming a polaron of nanometer dimensions.

No description available.