Jose Enedilton Medeiros Pereira

A thesis for the degree of Doctor of Philosophy defended in February 2018.

The PhD School of Science, Faculty of Science, X-ray and Neutron Science, Niels Bohr Institute, University of Copenhagen

Academic advisor:
Heloisa Nunes Bordallo

Hydrogen Bond Dynamics in Bioactive Molecules by Neutron Scattering and Density Functional Theory

This thesis presents results on hydrogen dynamics in systems with biological properties analyzed using a combination of neutron spectroscopy and density function calculations (DFT), further supported by calorimetric studies and Raman spectroscopy. The studied biomaterials were of increased complexity ranging from crystalline amino acid and antipsychotics drugs to confined water in human dentine and state of the art systems for oral delivery of the Hepatitis B protein antigen. To this end, the evolution of the hydrogen bonds in deuterated crystalline D-Alanine as a function of temperature was studied using neutron powder diffraction, polarized Raman scattering and ab initio calculations of the harmonic vibrational frequencies. 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 its enantiomeric form.

Another study focused on the analysis of antipsychotic drugs. Inelastic neutron scattering measurements supported by DFT calculations demonstrate that even if the agreement between calculated and experimental data is sufficiently good, only few vibrational features could be unambiguously assigned. This is a consequence of the intrinsic flexibility of the molecules. The main message of this study is that advances to the actual calculations for drug design should include detailed information on the hydrogen flexibility of the drug molecule, which might be obtained using the approach proposed in this work. From the study of water confined in human dentine, by combining neutron spectroscopy and thermal analysis we maintain the idea that hydroxyapatite protects the collagen in innate dentine. Finally, analysis of the dynamics of the vaccine protein HBSAg encapsulated in the bi-modal SBA-15 porous structure, cast light on the behavior of the distribution of HBsAg within the SBA-15 structure. The main objective of studying these different systems was to prove that combining INS to thermal analysis is a powerful tool to disentangle molecular motions in confinement and from the obtained information connect hydrogen dynamics to material’s property.