This Thesis deals with simulations of chiroptical spectra using a combination of molecular dynamics and quantum chemistry. Molecular dynamics was used to explore conformational behaviour of studied systems (proteins), quantum chemistry for calculation of spectral prop- erties. The Quantum chemical methods are limited to relatively small systems. We overcome this problem mostly by a fragmentation of studied systems, when smaller, computationally feasible, fragments are created and used for the quantum chemical calculations. Calculated properties were then transferred to the big molecule. Vibrational Optical Activity (VOA) spectra of poly-L-glutamic acid fibrils (PLGA), insulin prefibrillar form and native globular proteins were studied. The simulated spectra provided satisfactory agreement with the experiment and were used for its interpretation. Experimental Vibrational Circular Dichroism (VCD) spectra of poly-L-glutamic acid fibrils were only qualitatively reproduced by the simulation. We could reproduce the major amide I band and a smaller negative band associated with the side chain carboxyl group. Our simulation procedure was then extended to a set of globular proteins and their Raman Optical Activity (ROA) spectra. Here we achieved an exceptional precision. For example, we were able to reproduce...

1 Nucleotides are organic molecules that have a wide range of functions in living organisms. They participate in cell signaling, serve as cofactors of enzymatic reactions, play a central role in cellular metabolism, and are the basic monomeric units of nucleic acid polymers. Nucleotides consist of three subunit molecules - nitrogen nucleobase, a five-carbon sugar (ribose or 2'-deoxyribose), and a phosphate group containing one to three phosphates. The subject of this master thesis is the study of various nucleotides and their self-assemblies in water by means of vibrational spectroscopy - Raman scattering and its chirally sensitive variant Raman optical activity (ROA). ROA has the potential to provide new information about the structural arrangement, dynamics, and interactions of nucleotides, as it supposes to be much more sensitive to vibrations of its sugar part containing three to four chiral carbons, compared to Raman scattering. We study spectral manifestations associated with chemical modifications (difference between ribo- and deoxyribonucleotides, the influence of different phosphate positions) and the change of physical conditions (various charge states according to the set pH, effect of concentration, influence of ions). A substantial amount of work is devoted to studying the self-association of...

Studies of Lanthanide Complexes by a Combination of Spectroscopic Methods Monika Krupová (Department of Physical and Macromoecular Chemistry, Faculty of Science, Charles University in Prague) Since conventional structural analysis offers rather limited means for the chirality detection, a series of lanthanide tris-(β-diketonates) are investigated as effective receptors for a better chirality sensing in biomolecular substrates. These lanthanide complexes containing β-diketonate ligands are electrically neutral; they can further coordinate with various small organic molecules such as chiral alcohols, amino alcohols or amino acids in organic solvents and produce a strong chiral signal. Previously, a resonance in Raman scattering was observed in the studied systems due to the correspondence of europium electronic transition energy to the laser excitation wavelength, about a 100-fold signal enhancement if compared to non-resonant vibrational ROA was observed. This enabled shorter detection times as well as lower sample concentrations. In the current work, interaction of the Eu(FOD) complex with (R)- and (S)- enantiomer of 1-phenylethanol in n-hexane was studied using IR spectroscopy, Raman spectroscopy and Raman optical activity (ROA), UV-Vis spectroscopy and ultraviolet circular dichroism (UVCD). Only...

Cette thèse décrits la synthèse et caractérisations de chaines métalliques étendues (EMACs:extended metal atom chains) construite à partir des ligands dipyridylamine (dpa) etdipyridylformamidinate (DpyF). Le Chapitre I fait une brève introduction sur les liaisons métalmétalet sur les chaines métalliques étendues. Le Chapitre II présente les propriétés de conversionde spin (SCO: spin crossover) d’une série d’EMACs de tris-cobalt de formule générale[Co3(dpa)4X2]. L’influence des ligands axiaux et de la symétrie des molécules a été examinée etcorrélée aux propriétés de conversion de spin. Le Chapitre III porte sur la résolutionénantiomérique et activité RX optique de l’EMAC tris-cobalt [Co3(dpa)4(MeCN)2]2+. Dans lechapitre IV, La chimie de coordination du ligand N,N’-di(2-pyridyl)formamidinate (DpyF), quiconduit à des complexes présentant des propriétés structurales and magnétiques remarquable,est explorée. Finalement, le chapitre V présente nos études préliminaires pour obtenir despolymères unidimensionnelles d’EMAC de tris-cobalt en utilisant des radicaux de type thiazyle. / This thesis describes the synthesis and characterizations of extended metal atom chains (EMACs)supported by dipyridylamine (dpa) and dipyridylformamidinate (DpyF) ligands. Chapter Iprovides a brief introduction to metal-metal bonds and extended metal atom chains. In Chapter IIspin crossover properties of series of tricobalt EMACs based on [Co3(dpa)4X2] motifs arepresented. The influence of the axial ligands and the symmetry of the molecule was examined andcorrelated with the SCO properties. Chapter III describes the enantiomeric resolution and X-rayoptical activity of tricobalt EMAC, [Co3(dpa)4(MeCN)2]2+. In chapter IV, the coordination chemistryof N,N’-di(2-pyridyl)formamidinate, (DpyF) is explored, a ligand which gives rise to complexeswith remarkable structural and magnetic properties Finally, chapter V presents our initial effortsto obtain one-dimensional coordination polymers of tricobalt EMAC using thiazyl radicals.

Heterocyclen mit einer a-Hydroxycarbonyl-Einheit wie 3-Hydroxy-[1,5]-benzothiazepin-4-one oder 3-Hydroxychroman-4-one sind von Interesse, da sie Bestandteil von Pharmazeutika (z. B. Diltiazem®) oder Naturstoffen (z.B. die Flavonoide) sind. Ringtransformationen von optisch aktiven Glycidaten mit Binucleophilen stellen eine nützliche Synthesemethode zur Darstellung solcher Produkte dar. In Abhängigkeit von der Position des Angriffes des Nucleophiles am Oxiranring (a- oder b-Angriff) werden zwei Produkttypen mit verschiedenen Ringgrößen gebildet. Der Ablauf der Reaktion hängt vom Binucleophil, von den Substituenten am Oxiran und von den Reaktionsbedingungen ab. 4-Hydroxypyrazolidin-3-one werden bei der Reaktion von Glycidaten mit Hydrazinen gebildet. Reaktionen mit 1-Amino-2-mercapto-Verbindungen geben ausschließlich [1,4]-Thiazin-3-one. Gelenkt durch die Substituenten am Oxiran reagieren Glycidate mit o-Phenylendiaminen entweder zu Tetrahydro-chinoxalin-2-onen oder zu 3-Hydroxy-[1,5]-benzodiazepin-2-onen. Bei der Bildung der Tetrahydro-chinoxalin-2-one aus unsymmetrisch substituierten o-Phenylendiaminen wird eine hohe Regioselektivität beobachtet. Epoxyamide, gebildet aus Glycidsäuren und o-Aminophenol, cyclisieren unter basischen Bedingungen zu 1,4-Benzoxazin-3-onen, während in Gegenwart einer Lewis-Säure 3-Hydroxy-[1,5]-oxazepin-4-one gebildet werden. Reaktionen von Oxiran-carbonsäureamiden mit o-lithiierten Phenolderivaten führen zu Epoxyketonen, die zu 2-Alkyliden-cumaranonen oder 3-Hydroxychroman-4-onen transformiert werden können. Ohne Inanspruchnahme der Carbonylgruppe sind [1,4]-Benzoxazine durch die Reaktion von Glycidaten mit o-Aminophenolen erhältlich. Alle Ringtransformationen verlaufen stereoselektiv, so daß enantiomerenreine Produkte erhalten werden. / Heterocycles with an a-hydroxycarbonyl moiety such as 3-hydroxy-[1,5]-benzothiazepin-4-ones or 3-hydroxychroman-4-ones are of interest because they are frequently encountered in pharmaceuticals (e.g. Diltiazem®) or natural products (e.g. flavonoids). Ring transformation of optically active oxirane carboxylic acid derivatives with ambident nucleophiles provide a useful synthetic method for such type of products. Depending on the position of attack on the oxirane ring by the nucleophile (a- or b-attack) two types of products with different ring sizes are formed. The mode of reaction depends on the type of binucleophile, the substituents at the oxirane, and the reaction conditions. 4-Hydroxypyrazolidin-3-ones are formed in the reaction of glycidates with hydrazines. Reaction of 1-amino-2-mercapto nucleophiles exclusively afforded [1,4]-thiazin-3-ones. Governed by the substituents at the oxirane on the reaction of glycidates with o-phenylendiamines result either in tetrahydroquinoxalin-2-ones or 3-hydroxy-[1,5]-benzodiazepin-2-ones. In the formation of tetrahydroquinoxalin-2-ones from asymmetrically substituted o-phenylendiamines, high stereoselectivity was observed. Epoxyamides, formed from glycidic acids and o-aminophenols, cyclize to [1,4]-benzoxazin-3-ones under basic conditions while 3-hydroxy-[1,5]-oxazepin-4-ones are formed in the presence of a Lewis acid. Reaction of oxirane carboxylic acid amides with o-lithiated phenol derivatives afforded epoxyketones that could be transformed to 2-alkyliden-coumaranones and 3-hydroxychroman-4-ones. Without the use of the carbonyl group [1,4]-benzoxazines are available in the reaction of glycidates with o-aminophenols. All ring transformations were highly stereoselective giving enantiomerically pure products.

Optically active helical microparticles are studied in the forms of thin films, suspensions and powders. From fabricated helical porous thin films, microparticle suspensions are obtained by removing the microparticles (film columns) from their substrates and dispersing them into water. For removing microparticles, four methods are explored and compared: sacrificial NaCl layer, gold (Au) layer, buffered oxide etching, and direct ultrasonic agitation. The primary film material studied in this work is amorphous silicon (Si). Physical morphology of the microparticles is examined with scanning electron microscopy (SEM). Methods employed to characterize optical activity of the microparticles include: polarimetry, spectrophotometry, and spectroscopic ellipsometry (SE). The produced chiral microparticles exhibit optical activity: optical rotation (OR) and circular dichroism (CD - in the form of differential circular transmission (DCT)). Significant findings include: (a) we observe the largest optical rotatory power ever reported in scientific literature, 11◦/μm at 610 nm wavelength for a Si film; (b) for the helical thin films, there is one dominant DCT band in the measured wavelength range; however for microparticle suspensions and powders, there exist two DCT bands: one broad band at long wavelengths, and one narrow band in the short wavelength range; compared to their thin film forms, microparticle suspensions and powders have inverted sign for the broad DCT band. A discrete dipole approximation (DDA) model is employed to calculate optical response (e.g. extinction, scattering, and absorption cross-sections) of the microparticles, so as to enable us to understand the effects of different structural parameters of the microparticles on their optical response. Calculation confirms that optical activity of chiral microparticles is due to coherent light scatterings with the chiral structures of the particles. The inversion in sign of the broad DCT bands of microparticle suspensions and powders is likely due to the averaging effect from random orientation of the helical microparticles, as is indicated both from experimental results and from calculation. / Thesis (Ph.D, Physics, Engineering Physics and Astronomy) -- Queen's University, 2012-07-06 09:59:20.751

The thesis inquires the specific and advantageous applications of Raman optical activity (ROA) in wide range of diverse structural and conformational studies of biomolecules and other biologically important molecules. Our investigation was focused on several interconnected topics covering the fields of methodology, basic and applied research. The combination of experimental and theoretical approaches facilitated deeper understanding of studied phenomena, and allowed for the effects of solute-solvent interactions. High-quality spectra of model molecules in the C-H stretching region, acquired as a result of successful extension of ROA measurements to the whole region of fundamental molecular vibrations, enabled verification and further development of methods for ROA spectra simulations encompassing anharmonic corrections. Utilizing spirodilactams with highly nonplanar amide groups, we have traced the specific ROA spectral manifestations of amide nonplanarity. In case of antimicrobial peptide lasiocepsine, we have successfully simulated ROA signals of S-S stretching vibrations which contrary to current belief do not seem to reflect sense of the S-S group torsion. In larger molecular systems, we have better understood the process of the formation of stable polyproline II conformation and proved that ROA may...

Submitted by Claudinei Pracidelli (cpracide@ipen.br) on 2016-11-11T16:24:00Z No. of bitstreams: 0 / Made available in DSpace on 2016-11-11T16:24:00Z (GMT). No. of bitstreams: 0 / A operação dinamicamente estável com zonas conjuntas foi obtida para um ressonador laser contendo dois bastões de Nd:YAG com módulos laser comerciais. O ressonador não polarizado gerou 115 W de potência no modo transversal fundamental TEM00. Quando polarizado por lâmina de Brewster atingiu 100,5W de potência de saída com 91% de polarização. Quando o ressonador foi polarizado com um polarizador de filme fino, obteve-se melhora na qualidade de feixe e um aumento na polarização, com o valor de M2 sendo 1,56 e 1,84 nas direções x e y respectivamente com 95,4% de polarização. A potência de saída foi, ao nosso conhecimento, a mais alta obtida para lasers polarizados operando no modo fundamental e usando módulos lasers comerciais de Nd:YAG bombeados lateralmente por diodos sem nenhuma preparação especial. / Dissertação (Mestrado em Tecnologia Nuclear) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Dans une première partie de cette thèse, nous avons étudié le comportement sous champ électrique de la séquence de phases des "cristaux liquides smectiques chiraux" en développant une étude sous champ électrique (E) et en fonction de la température (T) qui sont deux variables thermodynamiques indépendantes. Les résultats de mesures ont conduit au tracé des diagrammes de phase Champ électrique-Température (E-T). Ces diagrammes peuvent dans certains cas révéler l'induction sous champ électrique de nouvelles phases n'existant pas à champ nul. D'autre part, suite à l'étude de certains composés présentant la phase ferroélectrique SmC* dans leur séquence de phase à champ nul. Le tracé de leurs diagrammes de phases (E-T) a permis de mettre en évidence un problème de coexistence entre une phase paraélectrique et une autre ferroélectrique. Pour bien localiser cette séquence de phases sans rencontrer ce phénomène de démixtion, on a fait appel à une nouvelle étude optique sans champ électrique basée sur la méthode de conoscopie à balayage. L'analyse de l'ellipticité de la lumière transmise en fonction de la rotation de l'échantillon a donné accès aux deux indices de réfraction (ne et no) séparément, à la biréfringence (?n), au pouvoir rotatoire optique (PRO) et à la gyrotropie. Ces études que nous avons développé avec succès nous permettent une mise au point robuste et efficace des comportements des différentes phases de cristaux liquides smectiques chiraux sous et en absence du champ électrique. / In the first part of this thesis, we studied the behavior of the phase sequence of "smectic chiral liquid crystals" in order to develop a study under electric field (E) and as a function of tempertaure (T) which are two independent thermodynamic variables. The measurement results allow us to establish the electric field versus temperature phase diagram (E-T). In some cases, the phase diagram, under electric field, can reveal the induction of new phase which is not existing at zero field. On the other hand, we investigated certain compounds with ferroelectric phase SmC* in their phase sequence at zero field. The delimitation of phase diagrams (E-T) helped to highlight a coexistence problem between a paraelectric phase and a ferroelectric one. To locate this phase sequence without encountering this demixing phenomenon, we used a new optical study without electric field based on scanning conoscopy method. The analysis of the ellipticity of the transmitted light depending on the rotation of the sample gave access to the two refractive indices (ne and no) seperately, the birefringence (?n), the optical rotatory power (ORP) and the gyrotropy. These studies that we have successfully developed enable us to develop a robust and effictive behavior of different phases of chiral smectic liquid crystals under and without electric field.

The polymeric gel-forming mucins provide the structural framework of saliva and the mucus barriers that cover the mucosal surfaces of the alimentary canal. Dietary compounds may influence the barrier properties of these protective layers. The effects of green tea polyphenols, which have many health benefits but have low bioavailability and contribute to the astringency of green tea, on the structural properties of the mucins in the alimentary canal are investigated here. Using well characterised, highly purified salivary mucins MUC5B and MUC7, and porcine gastric mucins, the effects of the green tea polyphenol epigallocatechin-3-gallate (EGCG) on mucins were studied here. Using rate-zonal centrifugation coupled to agarose gel electrophoresis, atomic force microscopy and particle tracking microrheology, EGCG, at concentrations found in a cup of green tea, caused increased aggregation of MUC5B in human whole saliva, and increased aggregation and viscosity of purified MUC5B. It was revealed using recombinant proteins of the N- and C-terminal regions of MUC5B that EGCG had these effects by aggregating the terminal globular protein domains of MUC5B. In contrast, MUC5B trypsin-resistant high molecular weight glycopeptides were not aggregated by EGCG, demonstrating that the oligosaccharide-rich, highly-glycosylated regions of mucins are not involved in the EGCG-induced aggregation of mucins. EGCG also caused the majority of MUC7 in human whole saliva to aggregate, and purified MUC7 also showed substantial aggregation in the presence of EGCG.Porcine gastric mucins were also used in order to model human gastric mucins. First, the identity of the porcine gastric mucins was explored using tandem mass spectrometry and immunohistochemistry. This revealed that Muc5ac was expressed by the surface epithelium and was the prominent mucin in porcine gastric mucus. Muc6 was expressed by gastric submucosal glands, but was not a major component of the secreted mucus barrier. Porcine Muc5ac and Muc6 were shown to be aggregated by EGCG. These data demonstrate that mucins from both saliva and the stomach are substantially altered by EGCG. This may contribute to the astringency and low bioavailability of EGCG. In contrast, the green tea polyphenol epicatechin (EC) did not cause aggregation of salivary mucins or porcine gastric mucins, suggesting that the galloyl ring of EGCG (which is absent in EC) is important for its aggregation of mucins, and that EC has different mechanisms of astringency. The structure of the mucins in the alimentary canal was studied using Raman spectroscopy, Raman optical activity (ROA) and Tip-enhanced Raman spectroscopy (TERS). The secondary structure of the oligosaccharide-rich regions of mucins was shown to be largely disordered, with some contribution of poly-proline II helix. The N- and C-terminal regions of MUC5B were largely β-sheet in structure, with some disordered structure also present in the C-terminal region. Raman spectroscopy could reliably distinguish between MUC5B glycoforms, demonstrating the sensitivity of this technique to mucin glycosylation and secondary structure. The first TERS spectra along the length of a MUC5B chain are reported, and suggest that patterns may exist in the glycosylation of MUC5B. Therefore, Raman spectroscopies are novel tools that shed new light on mucin structure and in future may be useful for studying the changes to mucin structure during interactions, such as those with polyphenols.