Intermolecular Hydrogen Bonds Studied by NMR Spectroscopy
| Název práce v češtině: | Mezimolekulové vodíkové vazby studované pomocí NMR spektroskopie |
|---|---|
| Název v anglickém jazyce: | Intermolecular Hydrogen Bonds Studied by NMR Spectroscopy |
| Akademický rok vypsání: | 2021/2022 |
| Typ práce: | rigorózní práce |
| Jazyk práce: | angličtina |
| Ústav: | Katedra organické chemie (31-270) |
| Vedoucí / školitel: | |
| Řešitel: | skrytý - zadáno a potvrzeno stud. odd. |
| Datum přihlášení: | 15.11.2021 |
| Datum zadání: | 15.11.2021 |
| Datum potvrzení stud. oddělením: | 13.12.2021 |
| Datum odevzdání elektronické podoby: | 15.11.2021 |
| Datum proběhlé obhajoby: | 17.01.2022 |
| Předběžná náplň práce |
| Studium intramolekulárních vodíkových vazeb mezi modifikovanými bázemi nukleových kyselin pomocí NMR experimentů. |
| Předběžná náplň práce v anglickém jazyce |
| Interactions between biomolecules and drugs are mostly controlled by weak intermolecular forces, particularly hydrogen bonds. The prevailing view of binding mechanisms has evolved from the early ‘lock-and-key’ hypothesis to the ‘induced fit’ model or conformational selection. The induced fit model postulates that exposure of a biomolecule to a substrate causes the biomolecule or the substrate to change structure in order to allow mutual binding. The structural adaptation involves most often conformational change, which may open the binding pocket or expose the biomolecular binding pattern to the substrate.
The aim of the diploma project is to bring new information about structural adaptations of biologically important molecules induced by a binding partner capable of hydrogen bonding. A methodology based on NMR experiments for the determination of free energy changes and structural changes upon hydrogen bond formation will be developed. The developed methods will be applied for gaining new insights into the induced-fit mechanism, and into the energetics and structural changes induced by intermolecular interactions of natural and modified nucleobases. The student will investigate hydrogen-bonding interactions between modified bases of nucleic acids, for example 2-methylaminoadenine. The model compounds will be synthesised in a collaborating lab. The order of the C–NHCH3 bond is higher than one in purine derivatives and two rotamers of the methylamino group should be observed by NMR spectroscopy at low temperature as two sets of signals. The orientation of the methylamino group in the rotamers can be unequivocally established with the help of long-range heteronuclear H–C coupling observed in HMBC experiment. Only one of the rotamers can form hydrogen-bonded complexes with molecules offering acceptor-donor-acceptor hydrogen-bonding pattern (e.g. thymine). If intermolecular complexes are formed, the equilibrium ratio of the rotamers will change. This rotamer-ratio change can be used for the calculation of ΔG of the hydrogen bonding interaction. A series of model compounds with methylamino substituents will be used for the determination of free energy changes upon the formation of hydrogen bonding complexes with natural and modified bases of nucleic. At the same time, these compounds may serve as a model for investigation of hydrogen bonding interactions of methylated nucleobases. DNA methylation is an epigenetic mechanism involved in many biological functions. For example, adenine N6 methylation has been demonstrated to regulate gene expression in eukaryotes and to be essential for the viability of prokaryotes. It has been hypothesised that adenine methylation reduces the base-pairing energy. |