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.

The proton dependent oligopeptide transporters (POT family) are members of the Major Facilitator Superfamily of secondary active transporter proteins. They use the transmembrane proton gradient to drive the uptake of di- and tripeptides into the cytoplasm. Members of the family are highly conserved in pro- and eukaryotic genomes, and in humans they are responsible for the oral absorption of many drug families, including -lactam antibiotics. Recently, the crystal structures of PepTSo and PepTSt, two prokaryotic homologues of the human proteins PepT1 and PepT2, captured the proteins in two distinct conformations, providing insight into the structural aspects of the transport mechanism. A protocol was designed for functional liposome reconstitution of POT proteins, and transport assays were conducted to characterise their substrate specificity, pH dependence and kinetic properties. Using site-directed mutagenesis, we identified binding site residues involved in peptide recognition and proton translocation, and distinguished between the two roles by comparing protein activity in proton- and peptide-driven conditions. We also investigated the roles of key residues in the conformational transitions that accompany the transport cycle, using data from biochemical assays, molecular dynamics simulations and modeling, as well as electron paramagnetic resonance measurements. In addition, several bacterial POT members were screened for crystallisation, in order to assess their stability and crystal diffraction quality in different detergents. Further work was performed with bacterial POT homologues YdgR and GkPOT, including binding studies using NMR spectroscopy and assaying drug transport in vivo and in vitro. Together, the data establish bacterial POTs as model systems for studying the mammalian oligopeptide transporters, and a mechanistic model for peptide transport is proposed.

The question posed in this work is how one would model and predict the rotational spectrum of open-shell open-shell van der Waals complexes. There are two secondary questions that arise: the nature of radical-radical interactions in such systems and the modelling of the large amplitude motion of the constituent molecules. Four different systems were studied in this work, each providing part of the answer to the main question. Starting with the large amplitude motion, there are two theoretical approaches that may be adopted: to either model the whole complex as a semi-rigid molecule, or to perform quantum dynamical calculations. We recorded and analysed the rotational spectrum (using Fourier transform microwave spectroscopy) of the molecule of tertiary butyl acetate (TBAc) which exhibits a high degree of internal rotation; and of the weakly-bound complex between a neon atom and a nitrogen dioxide molecule (Ne-NO2). We used the semi-rigid approach for TBAc and the quantum dynamical approach for Ne-NO2. We also explored the compatibility of these two approaches. Moreover, we were able to predict and analyse the fine and hyperfine structure of the Ne-NO2 spectrum using spherical tensor operator algebra and the results of our dynamics calculations. To explore the nature of the interactions in an radical-radical van der Waals complex we calculated the PESs of the possible states that the complex may be formed in, when an oxygen and a nitrogen monoxide molecule meet on a plane using a number of high level ab initio methods. Finally, our conclusions were tested and applied when we performed the angular quantum dynamics to predict the rotational spectrum of the complex between an oxygen and a nitrogen dioxide molecule, and account for the effect of nuclear spin statistics in that system.

This thesis investigates the mechanisms behind natural silk spinning by integrating rheology, spectroscopy and small angle scattering to better understand this process and to guide our efforts towards mimicking Nature’s ways of producing high performance fibres. As a result of natural selection, arthropods such as spiders and moths have evolved the ability to excrete silk proteins in a highly controlled manner. Spun from liquid feedstocks, silk fibres are used ex vivo to build structures with mechanical properties currently unmatched by industrial filaments. As yet, relatively little attention has been directed to the investigation of spinning under biologically relevant conditions. To better understand how and why silk is spun, this thesis bridges the gap between liquid silk flow properties and structure development. To directly connect the two, I have developed and deployed novel experimental platforms that combine infrared spectroscopy and small angle scattering with rheology. This approach has clarified long-standing ambiguities on the structural root of silk’s apparently complex flow properties. Small angle scattering revealed the length scales involved in the flow induced solidification under a range of spinning conditions. Mo reover, infrared spectroscopy offered a unique perspective into silk’s formation process immediately after excretion. In a similar manner to the post-extrusion tuning of the properties of partly solidified spider silk filaments, this thesis has revealed that silkworm silk fibres are far from completely formed once excreted. One might describe the filaments of mulberry silkworm as seeded molten polymers that form its hydrogen bonding network and crystallises slowly on site. Consequently, it enlightens that post-spinning conditions are equally paramount for silkworm silk, giving an explanation for the relatively poorer mechanical properties. The comparison of silks from a range of species, allowed this hypothesis to be extended to wild silkworm silk. My insights into spinning had the fortuitous repercussion of facilitating silk fibre solubilisation leading to the development of better artificial silk feedstocks flowing like native silks. With these findings, I believe we are now in an improved position to conceive artificial fibres with properties rivalling those of Nature.

No description available.

trans-2,5-Disubstituted-tetrahydrofurans (THFs) are a common structural motif in many biologically active natural products, particularly in the Annonaceous acetogenins. This thesis develops a new route for their synthesis and applies it to the total synthesis of the Annonaceous acetogenin sylvaticin. Chapter 1: Introduction – Synthetic routes to trans-2,5-substituted tetrahydrofurans This chapter reviews methods for the synthesis of trans-2,5-THFs that have been applied to natural products synthesis. Chapter 2: Results & Discussion – A Novel Route to trans-THFs The rearrangement of activated 2,5-disubstituted cis-THFs is reviewed and is developed into a new synthetic method for the synthesis of trans-THFs. The reaction proceeds via a hydride shift mechanism to form an oxonium ion. Intramolecular reduction by a tethered hydrosilane stereoselectively forms the trans-THF. The mechanism of the rearrangement is investigated with the use of different stereoisomers and a deuterium labelling study. A cross-over study is carried out which confirms the reaction occurs via the proposed hydride shift mechanism. Chapter 3: Introduction – The Annonaceous Acetogenins This chapter introduces the Annonaceous acetogenins, a biologically active class of natural products often found with THF rings in their structure. The three key areas for their synthesis are explored- the synthesis of the THF core, the synthesis of the butenolide ring, and their coupling. Chapter 4: Results & Discussion – The Synthesis of Sylvaticin The Annonaceous acetogenin sylvaticin is introduced, and its isolation in nature and biological activity reviewed. With the aid of a model system study to extend the scope of the reaction, the methodology developed in Chapter 2 is then applied to the synthesis of sylvaticin. The synthesis, the first to be reported, is completed in a total of 19 linear steps starting from commercially available tetradecatetraene. In order to prove the obtained structure is that found in nature, a comprehensive investigation is undertaken using Mosher ester derivatives and the synthesis of its bis-epimer, 4,36-epi,epi sylvaticin. Chapter 5: Experimental Full experimental procedures and characterisation of compounds are reported.

This thesis studies the monohydrate, dihydrate and in some cases, trihydrate of five carboxylic acids, namely acetic acid, propanoic acid, T-difluoroacetic acid, Gdifluoroacetic acid and trifluoacetic acid using the technique of Fourier tranform microwave spectroscopy. The rotational and centrifugal distortion constants of these hydrates were determined with high accuracy. Ab initio calculations were also performed to locate the different conformational minima of the hydrates and to optimize their structures. Comparison of the ab initio predicted rotational and centrifugal distortion constants with the experimentally observed values allows us to determine the structures of the global minimum conformations of the various hydrates without ambiguity. Hydrogen-bonded ring structures are found to be the predominant feature in all observed hydrates. In this structural arrangement, all the hydrogen bonds formed are located in the same ring, and the cooperativity effect between them significantly strengthens each hydrogen bond, as suggested by the sharp increase of their binding energies in the larger hydrates. The fine and hyperfine splittings observed in the specrum were also successfully analyzed, which allows information on the dynamics of the intramolecular large amplitude tunnelling motions to be extracted explicitly. In the final part of this thesis, the equilibrium constants for the formation of monohydrates of the different carboxylic acids involved in this thesis, together with that of formic acid whose microwave spectrum has been analyzed elsewhere, were calculated to approximately derive their abundances under typical atmospheric conditions. It was found that about 2% of FMA, ACA and PPA will complex with one H2O molecule to form monohydrates in the low troposphere, while for TFA, the value increases to about 15%, mainly as a result of the larger binding energy of TFA–(H2O) due to fluorination on the end group.

Spectroscopic measurements are detailed within this thesis, utilising incoherent neutron scattering to examine the dynamics of various condensed-matter systems, from nanosecond to sub-femtosecond timescales. The body of this work is divided into two distinct areas of research. I. Nuclear Momentum Measurements of Multiple Masses Deep inelastic neutron scattering (DINS) is used to probe the nuclear momentum distributions and kinetic energies of individual atomic species in sodium hydride (both in bulk and as nanoparticulates within a silica matrix), enriched lithium-7 fluoride and lithium tetra-ammoniate. Extension of DINS to examine heavier (M>4amu) nuclei is detailed, accomplished by the application of a simple stoichiometric fixing technique within the standard DINS theory and analysis protocols. The validity and accuracy of such simultaneous measurements are discussed. II. The Dynamics of Coordinated Ammonia in Zeolite A Inelastic neutron scattering (INS) and quasielastic neutron scattering (QENS) are utilised in the examination of vibrational and stochastic dynamics of the ammonia molecule, as coordinated to the internal surface of a zeolite host. Both sodium and copper-exchanged forms of zeolite-A are studied, with proton-weighted, low energy phonon-modes and rotational processes being observed and assigned.

This thesis presents applications of near infrared diode lasers to high resolution spectroscopy of transient radical species. Firstly, time resolved near infrared laser gain versus absorption is utilised in Chapter 2 to determine the I∗ quantum yield following ultraviolet photolysis of iodobenzene and its fluorinated analogues. The experimental method is first confirmed by comparison with literature values of the quantum yield for iodomethane photolysis, returning a quantum yield of Φ(I∗) = 0.71 ± 0.04 in good agreement with the literature, before being applied to determine the I∗ quantum yield following 248 nm and 266 nm photolysis of iodobenzene (Φ(I^∗) = 0.28 ± 0.04) and pentafluoroiodobenzene (Φ(I^∗) = 0.32 ± 0.05). The I^∗ quantum yields for 4-fluoroiodobenzene, 2,4-difluoroiodobenzene and 3,5-difluoroiodobenzene are also reported in order to determine the effect of selective fluorination on the dynamics of the photodissociation process. This work complements velocity-map ion imaging studies and spin-orbit resolved ab initio calculations of the ultraviolet photolysis of these compounds. Chapter 3 details the development of a narrow-bandwidth tunable continuous wave ultraviolet radiation source, through sum frequency mixing of tunable near infrared diode lasers with a fixed frequency, high powered, solid state laser. The application of the UV radiation source to spectroscopy of the A¹A₂ − X¹A₁ electronic band of formaldehyde is explored, where absolute absorption cross sections are determined for rotational transitions within the 220410 and 220430 vibronic bands. The sub-Doppler resolution has allowed refinement of the rotational constants for the slowly predissociating excited state of the 2²₀4³₀ vibronic band. The lifetimes of several rotational levels is determined to be in the range 0.74 ns to 1.46 ns. In Chapter 4 the UV radiation source developed in Chapter 3 is applied to the A ²Σ⁺ − X ²Π electronic band of the OH radical. Firstly, this source is utilised to probe a continuous supply of hydroxyl radicals using cavity-enhanced absorption spectroscopy and wavelength modulation spectroscopy. Pressure induced broadening parameters for the Q₁(2) rotational transition for He, Ne, Ar and N₂ buffer gases are also measured. Following the successful application of this source to probe a continuous OH source at atmospheric pressure, the UV spectrometer is used to probe OH radicals from nitric acid photolysis at 193 nm, where the nascent speed distribution and Doppler lineshape is shown to be in excellent agreement with the literature. Time resolved absorption spectroscopy of the nascent OH fragment also returns a translational relaxation constant of k_trans = (3.85±1.06)×10⁻¹⁰cm³molecule⁻¹s⁻¹, which is in good agreement with literature values. These preliminary results indicate the potential of this narrow-bandwidth tunable UV source as an absorption-spectroscopy-based probe of nascent Doppler profiles. Chapter 5 presents the application of frequency-modulated radiation from a near infrared diode laser as a probe of the angular momentum polarisation of the nascent CN fragments, produced by 266 nm photolysis of ICN. These CN fragments are probed in the high rotational states of both the ground and first excited vibrational level on the A ²Π − X ²Σ⁺ electronic transition; in particular these constitute the first measurements of alignment and orientation in the first excited vibrational level at this photolysis wavelength. The alignment parameters reported for both vibrational levels are comparable, indicating that the incoherent dynamics contributing to their formation are the same. In contrast, the orientation of the v = 1 CN fragment is shown to be of opposite sign to that of v = 0 at this photolysis wavelength, although the absolute differences in their orientation parameters are similar to that observed for photolysis at 248 nm. This observation is consistent with coherent orientation arising from phase differences between wavepackets propagating on multiple excited potential energy surfaces.

Currently, pupils' interest in science continues to decline, although this area of education is very important in every day life (medicine, environment, etc.) and there is high demand for science professions on the labor market. Molecular biology curriculum concerning DNA and the transfer of genetic information is abstract and difficult topic for pupils to imagine, and for teachers to explain. There are many ways to teach this topic. Very popular are iquiry and laboratory practise. But not all schools have their own laboratories, and can teach molecular practical effectivelly. Inquiry based teaching is time consuming to prepare, and not every topic is appropriate to be taught this way. Another possibilities how to visualize "invisible" molecules and processes are computer software and animations or 3D physical model. In my thesis, I examined the effect of using computers and animations to teach abou DNA compared to using a 3D physical model on students' knowledge. I laso tested the possible influence of gender and pupils' preferences on their achieved score on knowledge tests. The research was performed in five classes at three high schools in Prague. Students in year 12 were on different types of high school and some of them took special biology class, their age was between 15 and 18 years. The...