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Studies of Lanthanide Complexes by a Combination of Spectroscopic Methods
Krupová, Monika ; Bouř, Petr (advisor) ; Kapitán, Josef (referee)
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...
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Characterisation of polyproline I secondary structure by means of vibrational and chiroptical spectroscopy methods and quantum mechanical simulations
Vančura, Martin ; Profant, Václav (advisor) ; Hudecová, Jana (referee)
Our investigation was focused on a secondary protein structure called polyproline I. This helical structure has been known for a long time, but its occurrence and significance in nature is not yet fully known. In this thesis, we use Raman spectroscopy and chiral sensitive Raman optical activity. These methods are sensitive to the structure of proteins but are more informative and sensitive to the local arrangement than the commonly used ECD and UV absorption. We were able to obtain polyproline I Raman and ROA spectra that have not yet been published. We have described important differences between the spectra of polyproline I and II and observed the process of mutarotation. The experimental part of the work is supplemented by quantum chemistry calculations of spectra using the transfer of molecular property tensor. The calculated spectra corresponded very well with the experimental spectra.
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Raman optical activity and conformational flexibility of peptides in solution
Hrudíková, Jana ; Baumruk, Vladimír (advisor) ; Kapitán, Josef (referee)
Title: Raman optical activity and conformational flexibility of peptides in solution Author: Jana Hrudíková Department: Institute of Physics of Charles University Supervisor: Doc. RNDr. Vladimír Baumruk, DrSc. Supervisor's e-mail address: baumruk@karlov.mff.cuni.cz Abstract: Molecular flexibility can significantly modify Raman and ROA spectral intensities, band positions and the ROA signs. Taking into account dynamic aspects of behavior of studied molecules in solution via conformational averaging therefore seems to be crucial for spectral interpretation. The first of studied models, histidine, plays an important role in metallo-enzymatic reactions and peptide folding, due to its imidazole ring. ROA spectra of His at different pH, His complexed with Cu2+ and dipeptides His- Gly and Gly-His were recorded on the spectrometer built at the Institute of Physics of the Charles University as a first step of the subsequent study. The second studied system, a cyclic hexapeptide c-(Phe-D-Pro-Gly-Arg-Gly-Asp), serves as a convenient model for β- hairpin and anti-parallel β-sheet. It was previously studied by means of VCD and IR. From molecular dynamics simulations 10 peptide geometries were selected for spectral modeling. The Raman and ROA spectra were calculated ab initio. For a model fragment Phe-D-Pro, which...
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Raman optical activity of biomolecules: From simple models to complex systems
Pazderková, Markéta ; Baumruk, Vladimír (advisor)
The aim of the thesis is to utilize Raman optical activity (ROA) to get unique information on peptide/protein conformation, which is otherwise difficult or even impossible to obtain. We have focused on investigation of amide and disulfide groups. Utilizing tailor-made model structures (rigid tricyclic spirodilactams with two interacting nonplanar amide groups), special model peptides and even biologically active molecules (neurohypophyseal hormones and their agonistic and antagonistic analogs, antimicrobial peptide lasiocepsin and its analogs having different disulfide pattern) we have traced specific spectral manifestation of nonplanar amides and disulfides. ROA results were supplemented by data obtained by complementary chiroptical methods - electronic (including vacuum UV - SRCD) and vibrational circular dichroism. When used in a concerted fashion, these techniques provide complex information on peptide/protein secondary structure. Where possible, experimental chiroptical data were compared to ab initio calculations. In chiroptical spectra we have found and interpreted signals reflecting nonplanarity of the amide group. Moreover, in ROA spectra we have identified signals due to S-S stretching vibrations which seem to reflect sense of the disulfide group torsion.
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Raman optical activity and conformational flexibility of peptides in solution
Hudecová, Jana ; Baumruk, Vladimír (advisor)
Title: Raman optical activity and conformational flexibility of peptides in solution Author: Jana Hrudíková Department: Institute of Physics of Charles University Supervisor: Doc. RNDr. Vladimír Baumruk, DrSc. Supervisor's e-mail address: baumruk@karlov.mff.cuni.cz Abstract: Molecular flexibility can significantly modify Raman and ROA spectral intensities, band positions and the ROA signs. Taking into account dynamic aspects of behavior of studied molecules in solution via conformational averaging therefore seems to be crucial for spectral interpretation. The first of studied models, histidine, plays an important role in metallo-enzymatic reactions and peptide folding, due to its imidazole ring. ROA spectra of His at different pH, His complexed with Cu2+ and dipeptides His- Gly and Gly-His were recorded on the spectrometer built at the Institute of Physics of the Charles University as a first step of the subsequent study. The second studied system, a cyclic hexapeptide c-(Phe-D-Pro-Gly-Arg-Gly-Asp), serves as a convenient model for β- hairpin and anti-parallel β-sheet. It was previously studied by means of VCD and IR. From molecular dynamics simulations 10 peptide geometries were selected for spectral modeling. The Raman and ROA spectra were calculated ab initio. For a model fragment Phe-D-Pro, which...
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Characterisation of polyproline I secondary structure by means of vibrational and chiroptical spectroscopy methods and quantum mechanical simulations
Vančura, Martin ; Profant, Václav (advisor) ; Hudecová, Jana (referee)
Our investigation was focused on a secondary protein structure called polyproline I. This helical structure has been known for a long time, but its occurrence and significance in nature is not yet fully known. In this thesis, we use Raman spectroscopy and chiral sensitive Raman optical activity. These methods are sensitive to the structure of proteins but are more informative and sensitive to the local arrangement than the commonly used ECD and UV absorption. We were able to obtain polyproline I Raman and ROA spectra that have not yet been published. We have described important differences between the spectra of polyproline I and II and observed the process of mutarotation. The experimental part of the work is supplemented by quantum chemistry calculations of spectra using the transfer of molecular property tensor. The calculated spectra corresponded very well with the experimental spectra.
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Vibrational spectroscopy of pharmacologically important molecules: Study of L-DOPA and its deuterated derivatives
Spasovová, Monika ; Profant, Václav (advisor) ; Kaminský, Jakub (referee)
L-3,4-dihyroxyphenylalanine (L-DOPA, levodopa) is a gold standard treatment of Parkinson's disease. Lately, it has been found that some of its deuterated analogues exhibit higher potency in the treatment; thus, they could replace L-DOPA. The subject of this thesis was a study of L-DOPA and its deuterated derivatives by the means of vibrational spectroscopy (Raman, ROA, IR, and VCD) and a comparison of the experimental results to a quantum mechanical simulations of the spectra. ROA and VCD are chiroptical methods, thus they are suitable for measurement of chiral molecules amongst which L-DOPA indeed belongs. Thanks to the quantum chemistry calculations, which yielded spectra with a very good agreement with the experiment, we were able to assign experimental spectral features to individual vibrational modes of the L-DOPA. The use of chiroptical techniques (mainly ROA) enabled an assignment of an absolute configuration of double deuterated derivative of L-DOPA, α,β-D2-L-DOPA. It reviled that it occurs in a (S-α,S-β)-enantiomeric form.
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Vibrational optical activity of 3-aminoquinuclidine
Jílek, Štěpán ; Profant, Václav (advisor) ; Kaminský, Jakub (referee)
1 The bachelor thesis deals with the study of the chiral molecule 3-aminoquinuclidine (AQN), which is an important pharmacophore. The derivates of this molecule form a basis for several biologically important molecules and drugs: serotonin receptors activity modulators, agents displaying neuronal activity and medicaments supressing side effects of chemotherapy administration (antiemetics). AQN is a chiral molecule and information on its absolute configuration and enantiomeric purity is crucial to the use of AQN in drug synthesis. AQN contains both primary and tertiary amine group and depending on pH value it can be found in three differently charged forms. This thesis presents characterization of AQN utilizing methods of vibrational spectroscopy - infrared absorption and Raman scattering, together with their variants - vibrational circular dichroism (VCD) and Raman optical activity (ROA), all these in combination with quantum chemical simulations. The attention was paid to a choice of the suitable solvents and settings of experimental conditions. Based on pH dependent Raman spectral series we determined pKA dissociation constants associated with transitions between AQN's protonated states, which were further characterized by ROA and VCD. The properties of AQN in various phases (aqueous solution, crystalline...
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Theory and application of optical spectroscopic methods for structural molecular studies
Hudecová, Jana ; Bouř, Petr (advisor) ; Setnička, Vladimír (referee) ; Valenta, Jan (referee)
Title: Theory and application of optical spectroscopic methods for structural molecular studies Author: RNDr. Jana Hudecová Department / Institute: Institute of Organic Chemistry and Biochemistry Supervisor of the doctoral thesis: Prof. RNDr. Petr Bouř, DSc. Abstract: In the thesis, methods of the chiroptical spectroscopy (Raman optical activity, electronic and vibrational circular dichroism, circularly polarized luminescence) were utilized to obtain information on structure of chiral molecules. In four main projects, we focused on improving accuracy of quantum-chemical computations used for interpretation of experimental spectra by including anharmonic effects, solvent, molecular flexibility and dynamics. In the first project, the normal mode geometry optimization method was investigated and a suitable frequency limit providing realistic vibrational band broadening was found. Then the ability of harmonic and anharmonic computational approaches to describe the C-H stretching vibrations was explored for three terpene molecules and four spectroscopic methods. In the third project, we estimated the role of dispersion forces and different organic solvents for conformer equilibria and dynamics of cyclic dipeptides containing tryptophan. In the last project, circularly polarized luminiscence spectra, which were...
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Structure and dynamics of peptides and proteins in solution: application of Raman optical activity
Profant, Václav ; Baumruk, Vladimír (advisor) ; Kapitán, Josef (referee) ; Setnička, Vladimír (referee)
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...
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