|
|
Development of new methodology for accurate determination of molecular geometry
Socha, Ondřej ; Dračínský, Martin (advisor) ; Munzarová, Markéta (referee) ; Hrabal, Richard (referee)
This thesis employs the combined strengths of Nuclear Magnetic Resonance (NMR) and computational methodologies to investigate chemical phenomena that influence molec- ular structure across the solid, liquid, and gas states. In the solid phase, the research focuses on chlorine quadrupole couplings, and their use in structure analysis, highlight- ing the advantages of NMR in conjunction with Density Functional Theory for data interpretation. In the liquid state, the tautomeric conversion of isocytosine is examined, underlining the role of NMR in analyzing intricate chemical exchanges. The gas phase study explores the dimerization of acetic acid using NMR, addressing previous inconsis- tencies and evaluating calculations of molecular structure and properties. The combined use of NMR and computational techniques has been instrumental in resolving existing discrepancies and providing a deeper understanding of these chemical systems. The find- ings underscore the importance of careful data interpretation and emphasise the strengths and constraints of the combined methodologies. 1
|
|
|
Dynamics of paramagnetic complexes observed by Nuclear Magnetic Resonance
Blahut, Jan ; Hermann, Petr (advisor) ; Botta, Mauro (referee) ; Dračínský, Martin (referee)
In this Thesis, structure and dynamics of paramagnetic complexes for medical application are studied by Nuclear Magnetic Resonance (NMR). It focuses mainly on development of contrast agents (CA) for Magnetic Resonance Imaging (MRI) which is one of the most effective radiodiagnostic method nowadays. Most of the MRI CAs contains paramagnetic complexes of d- and f-metal ions. The presence of unpaired electron in proximity of NMR active nuclei has two main effects: paramagnetically induced shift and paramagnetically induced relaxa- tion. Both processes can dramatically change the NMR spectrum and often make it unobservable at all. Nevertheless, in many cases, acquisition of such spectra is possible and sometimes even less time-consuming than observation of diamag- netic molecules. Enhanced T1 relaxation allows faster pulse sequence repetition and increased chemical shift dispersion may lead to resolution of originally over- lapped signals. Moreover, the analysis of paramagnetic effects can provide useful information about the structure and dynamics of the studied system. Theoretical background of these effects is described in the Introduction of the Thesis. In the first part of Discussion in the Thesis, a new class of contrast agents for 19F-MRI based on nickel(II) and cobalt(II/III) ions is introduced...
|
|
|
NMR study of solution dynamics of LnIII complexes of monophosphorus H4dota analogues
Svítok, Adam ; Hermann, Petr (advisor) ; Dračínský, Martin (referee)
Lanthanides have several specific properties which cannot be found for other elements in the periodic table. Among various applications of lanthanides, complexes of LnIII ions are used in medicine, e.g., as contrast agents in MRI, as luminescent probes or as radiopharmaceuticals, where their specific properties are important. These complexes must be kinetically inert to prevent release of highly toxic "free" LnIII ions. This requirement is fulfilled with pre-organized ligands such as analogues of H4dota (1,4,7,10- tetraazacyclododecane-1,4,7,10-tetraacetic acid). Many of important properties of LnIII complexes of H4dota, such as relaxivity, isomerism and fluxionality, depend on the solution dynamics of the complexes. However, the knowledge of this solution dynamics is limited for LnIII complexes of H4dota derivatives with phosphonate or phosphinate pendant arms. Recently, a new dynamical process where phosphonate oxygen atoms interchange through a bidentate phosphonate intermediate ("a phosphonate rotation") has been proposed by DFT calculations but unconfirmed experimentally. To prove the process experimentally, solution dynamics of LnIII complexes of monophosphonate and monophosphinate derivatives of H4dota was investigated. Especially, to examine the "P-rotation", 17 O NMR spectroscopy was used...
|
|
|
Intermolecular Hydrogen Bonds Studied by NMR Spectroscopy
Osifová, Zuzana ; Dračínský, Martin (advisor) ; Blahut, Jan (referee)
N-methylation of nucleic acids is one of the most important epigenetic mechanisms in organisms and viruses and it is observed in connection with physiological or pathological processes in human body. For example, the N- methylation of adenine to give N6 -methyladenine is associated with development of obesity or Alzheimer disease. These systems can be successfully studied by low- temperature NMR spectroscopy because the bond between a purine ring and its substituent has a significant double-bond character and, due to restricted rotation around this bond, two sets of signals are observed in low-temperature NMR spectra. This diploma thesis is focused on research of N-methylated nucleobases' rotamer equilibria and the free-energy changes associated with the hydrogen-bonded base pair formation via simple and straightforward method based on NMR spectroscopy monitoring. We proved that the rotamer equilibria of N-methylated adenine derivatives are dependent on temperature, solvent and bonding partner concentration. We also obtained the geometry of formed intermolecular complexes of N-methylated adenine derivatives with thymine and the free-energy changes associated with their formations via newly developed method based on chemical shift changes dependent on bonding partner concentration. All obtained data...
|
|
|
Ordering, transport and rotational dynamics of adsorbed carbon dioxide in metal-organic framework Zn2(BDC)2(DABCO)
Peksa, Mikuláš ; Lang, Jan (advisor) ; Bulánek, Roman (referee) ; Dračínský, Martin (referee)
The work analyzes the dynamics of carbon dioxide adsorbed in crystals of anisotropic metalo-organic frameworks Zn2(BDC)2(DABCO). It utilizes nuclear magnetic resonance methods, namely, the 13 C spetroscopy, the PFG method and the measurement of longitudinal relaxation times. Experimental data are compared with calculation of molecular dynamics. The thesis provides a theoretical model for explaining the temperature dependence of the residual anisotropy of the chemical shift observed in the spectra. The method of measuring diffusion anistropy based on the change of the shape of the 13 C spectra is described. The work determines the theoretical course of dependence of the longitudinal relaxation time on temperature using Redfield's theory. Times characterizing dynamic processes running on a picosecond scale that determine the dynamics of the fluid as a whole are evaluated from the data. 2
|
|
|
17O NMR study of LnIIIcomplexes of H4do3apOEt ligand
Svítok, Adam ; Hermann, Petr (advisor) ; Dračínský, Martin (referee)
Macrocyclic complexes of H4dota-like ligands are used in various fields, mainly in medicine. e. g. as MRI contrast agents or luminescent probes. Their applications are greatly influenced by stereochemistry. Stereoisomers of these complexes mostly interconvert with each other in solution. This interconversion can be studied by NMR spectroscopy This work is intended to test 17 O NMR spectroscopy as a tool for monitoring dynamic processes where phosphonate group in the complexes of methylphosphonate derivatives of H4dota is involved. To this end, ligand H4do3apOEt and his LnIII -complexes (Ln ≠ Pm) containing 17 O-labeled phosphonate group were synthesized. Next, 17 O NMR spectra of these complexes were measured and analysed. In an analogy with H4dota complexes, signals of both non-coordinated and coordinated oxygen atoms (except GdIII ) in the complexes could be detected. Fraction of TSA (twisted square-antiprism) and SA (square-antiprism) isomers was determined from the acquired 17 O NMR spectrum for each complex. The determined values were compared with those obtained by analysing 1 H and 31 P NMR spectra of the complexes, which were also measured. The TbIII , DyIII and YbIII complexes (because of high resolution of their 17 O NMR spectra) and CeIII complex (because of anomalous properties of its...
|
|
|
Separation of rotamers of 5-nitrosopyrimidines by capillary electrophoresis
Štěpánová, Sille ; Procházková, Eliška ; Čechová, Lucie ; Žurek, Jiří ; Janeba, Zlatko ; Dračínský, Martin ; Kašička, Václav
A new capillary electrophoresis (CE) method was developed for the separation of a new type of stereoisomers - rotamers of polysubstituted 5-nitrosopyrimidine derivatives. Partial separation of some rotamers was obtained in sodium borate, pH 9.3, or in Tris-phosphate, pH 2.2, background electrolytes (BGEs) free of cyclodextrins (CDs). However, the best, baseline separations of the rotamers of 5-nitrosopyrimidines were achieved in sodium borate BGE, pH 9.3, containing 20 mg/mL beta-CD as stereoselector, or in Tris-phosphate BGE, pH 2.2, with carboxymethyl-beta-CD as stereoselector.
|
|
|
Dynamics of paramagnetic complexes observed by Nuclear Magnetic Resonance
Blahut, Jan ; Hermann, Petr (advisor) ; Botta, Mauro (referee) ; Dračínský, Martin (referee)
In this Thesis, structure and dynamics of paramagnetic complexes for medical application are studied by Nuclear Magnetic Resonance (NMR). It focuses mainly on development of contrast agents (CA) for Magnetic Resonance Imaging (MRI) which is one of the most effective radiodiagnostic method nowadays. Most of the MRI CAs contains paramagnetic complexes of d- and f-metal ions. The presence of unpaired electron in proximity of NMR active nuclei has two main effects: paramagnetically induced shift and paramagnetically induced relaxa- tion. Both processes can dramatically change the NMR spectrum and often make it unobservable at all. Nevertheless, in many cases, acquisition of such spectra is possible and sometimes even less time-consuming than observation of diamag- netic molecules. Enhanced T1 relaxation allows faster pulse sequence repetition and increased chemical shift dispersion may lead to resolution of originally over- lapped signals. Moreover, the analysis of paramagnetic effects can provide useful information about the structure and dynamics of the studied system. Theoretical background of these effects is described in the Introduction of the Thesis. In the first part of Discussion in the Thesis, a new class of contrast agents for 19F-MRI based on nickel(II) and cobalt(II/III) ions is introduced...
|
|
|
Synthesis of ellipticine derivatives and study of their interactions with DNA
Dračínský, Martin ; Sejbal, Jan (advisor) ; Klinot, Jiří (referee) ; Lyčka, Antonín (referee) ; Rosenberg, Ivan (referee)
CONCLUSIONS t New strategy for ellipticine synthesis was proposed' The yields of the synthesis are very hígh and pure product is obtained. The strategy was verified with the synthesis of other ellipticine derivatives' rBenzylicoxidationsoťellipticineandl,4-dimethylcarbazolewerestudiedand13. hydroxyellipticine was slnthesised' ' Three empirical potentials were compared with reference ab initio data of ellipticine derivative - DNA base patr' . The ernpirical potentials calculate interaction energies of the complexes quite well (espeglallytheA-ffE6andtheLHpotentials)buttheyfailinthesearchofglobal energy minima geometri es' .Interactionsofellipticineandg.hydroxyellipticinewithtwooligonucleotideswerc studiedintwobuffers(weaklyacidicandneutral,ellipticineisprotonatedintlro acidic buffer). Using two-dimensional NMR techniques assignment of all hydrogen signals of oligonucleotides CGCTAGCG and ATAGCTAT was done. The most important interaction of the ellipticine derivatives with the oligonucleotides is intercalation, but in the acidic buffer ellipticine can form also non-intercalative (bond to the minor or to the major groove) complexes with the oligonucleotides. Both ellipticine derivatives destabilised the duplex structuÍe of the oligonucleotide ATAGCTAT in acidic environment. ln the neutral buffer the life-time...
|
|
|
Struktura a vlastnosti modifikovaných složek nukleových kyselin
Procházková, Eliška ; Dračínský, Martin (advisor) ; Lyčka, Antonín (referee) ; Hrabal, Richard (referee)
Modified nucleic acid components (nucleotides, nucleosides, nucleobases) display a wide range of biological activities such as antiviral, cytostatic, antimicrobial or antioxidative. Many of them are successfully used in clinical practice, for instance as anti-HIV drugs or in hepatitis B treatment. The first precondition for understanding biological effects is to evaluate the chemical structure as well as the conformation of the studied compounds correctly. For this purpose, solution-state nuclear magnetic resonance (NMR) spectroscopy in combination with mass spectrometry is the most frequently used method. Not only the structure, but also physico- chemical properties can be investigated using NMR spectroscopy, for instance, conformational changes, tautomeric forms, protonation sites, acido-basic properties, non-covalent interactions, isotopic exchanges or interactions with biomolecules. Similarly to solutions, NMR spectroscopy can be employed in studies of nucleic acid components (NACs) in solid state. This technique found assertion after computational-chemistry methods development during the last decades. Different solid-state structures (polymorphic forms) or dynamics of these compounds can be established by solid-state NMR spectroscopy in combination with quantum-chemical calculations. In this...
|
guest ::
