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Record Id 45111299
Title Hydrogen Bond Dynamics in Bioactive Molecules by Neutron Scattering and Density Functional Theory
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Abstract This thesis presents results on hydrogen dynamics in different systems of molecules with biological properties, analyzed using a combination of neutron spectroscopy and density function calculations (DFT). These investigations are further supported by calorimetric studies, structural analysis and Raman spectroscopy. The principle aim of the studies carried out during the 3 years of this project was to widen the applications of neutron techniques in the study of molecules of biological interest. To this end, the evolution of the hydrogen bonds in deuterated crystalline D-Alanine (C3D7NO2) as a function of temperature was studied using neutron powder diffraction, polarized Raman scattering and ab initio calculations of the harmonic vibrational frequencies. The findings using this approach produced one publication in IUCrJ, appended as Paper 1 of this thesis. The results show changes in the number of vibrational modes as a function of temperature caused by dissimilarities in the structural properties of D-Alanine compared to enantiomeric form L-Alanine. Another subject of the study was the analysis of the antipsychotics drugs haloperidol (C21H23ClFNO2), aripiprazole (C23H27Cl2N3O2), and quetiapine hemifumarate (C21H25N3O2S · 0.5C4H4O4), chosen based on similarities in their structures and function. The aims were to look for any relationship between the crystalline stability and dynamics of these molecules and to add such information to molecular dynamics simulations. To this end, inelastic neutron scattering measurements were supported by density functional theory calculations, while conformational transformations and the purity of the samples were determined from X-rays and calorimetric studies. The outcome of this work resulted in Paper 2, also appended to the thesis, which is currently in preparation for journal submission. Considering that neutron spectroscopy is highly sensitive to identifying hydrogen in biological samples, studies of the hydrogen mobility within innate and demineralized human dentine were performed combining the elastic fixed window approach and thermal analysis. This work sought to gather additional information on the states of water within the dental hard tissues. Our findings support the idea that hydroxyapatite protects the collagen in innate dentine. Demineralized dentine, on the other hand, acts as a sponge where free, bulk-like water is trapped. This research resulted in a BSc thesis that I co-supervised and in Paper 3 (appended) that is under peer review in The Journal of Dental Research. Analysis of the dynamics of the Hepatitis B surface antigen (HBsAg) encapsulated in the mesostructured porous silicate Santa Barbara Amorphous (SBA-15) was also carried out, using calorimetric studies combined with quasi-elastic neutron scattering and the elastic fixed window approach. These very preliminary findings cast light on the behavior of the distribution of HBsAg within the SBA-15 structure. The main results are presented in Paper 4 (appended), submitted to the Special Topics (ST) issue on the theme “Physics Inspired by Living Matter: Dynamics, Topology and Functionality” of the 2017 Geilo School in the European Physical Journal (EPJ). The final scientific contribution presented in this thesis is a book chapter that summarizes results from neutron powder diffraction and inelastic neutron scattering on different crystalline amino acids, such as L-alanine (C3H7NO2), L-valine (C5H11NO2) and L-leucine (C3H7NO2). The main outcome of this book chapter is a summary of how small variations in the hydrogen bond network correlate to conformation changes in these structures.
Organisation ISIS , ISIS-TOSCA , STFC
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Language English (EN)
Type Details URI(s) Local file(s) Year
Thesis PhD, University of Copenhagen, 2018. https://www.nbi.k…Medeiros_Pereira.pdf 2018