Studies Towards Nucleic Acids at the Origins of Life

Nucleic acids are at the heart of extant biology and the structure of life’s original genetic polymer is still a question of debate. The RNA world theory proposes that RNA was the first nucleic acid employed as life’s genetic polymer due to its dual ability as informational storage (genotype) and primordial catalyst (phenotype). However, ribonucleotides are complex chemical structures, and simpler or more stable nucleic acids, such as threose nucleic acid (TNA) or DNA, can also carry genetic information. In principle, nucleic acids like TNA could have played a vital role in the origins of life but the advent of any genetic polymer requires synthesis of its monomers. This work demonstrates a high-yielding, stereo-, regio- and furanosyl-selective prebiotic synthesis of threo-cytidine, an essential component of TNA. This work uses key intermediates (aminooxazolines) and reactions previously exploited in the prebiotic synthesis of the canonical pyrimidine ribonucleoside cytidine. It avoids the low yielding glycosylations that have previously been demonstrated for constructing nucleic acids and utilises and efficient photochemical anomerization that is enabled by selective anhydronucleoside thiolysis. This work also demonstrates that erythro-specific 2',3'-cyclic phosphate synthesis provides a mechanism to photochemically select TNA cytidine and suggests that TNA may have coexisted with RNA during the emergence of life. This thesis also investigates whether DNA be delivered simultaneously with RNA, the co-emergence of both would further probe the place and importance of DNA at the origin of life. This work expands on previous work towards DNA and examines the role of irreversible thiol addition to anhydronucleosides as a route towards DNA precursors. Finally, the question of why the nucleobases present in extant biology (A, G, C, U/T) were chosen is addressed. This work explores the paradigm of UV stability as a selection pressure and the results contrast with current thinking that the purine nucleobases were chosen for their ability to resist degradation by UV-light

Nuclear Magnetic Resonance (NMR) Spectroscopic Characterization of Nanomaterials and Biopolymers

abstract: Nanomaterials have attracted considerable attention in recent research due to their wide applications in various fields such as material science, physical science, electrical engineering, and biomedical engineering. Researchers have developed many methods for synthesizing different types of nanostructures and have further applied them in various applications. However, in many cases, a molecular level understanding of nanoparticles and their associated surface chemistry is lacking investigation. Understanding the surface chemistry of nanomaterials is of great significance for obtaining a better understanding of the properties and functions of the nanomaterials. Nuclear magnetic resonance (NMR) spectroscopy can provide a familiar means of looking at the molecular structure of molecules bound to surfaces of nanomaterials as well as a method to determine the size of nanoparticles in solution. Here, a combination of NMR spectroscopic techniques including one- and two-dimensional NMR spectroscopies was used to investigate the surface chemistry and physical properties of some common nanomaterials, including for example, thiol-protected gold nanostructures and biomolecule-capped silica nanoparticles. Silk is a natural protein fiber that features unique properties such as excellent mechanical properties, biocompatibility, and non-linear optical properties. These appealing physical properties originate from the silk structure, and therefore, the structural analysis of silk is of great importance for revealing the mystery of these impressive properties and developing novel silk-based biomaterials as well. Here, solid-state NMR spectroscopy was used to elucidate the secondary structure of silk proteins in N. clavipes spider dragline silk and B. mori silkworm silk. It is found that the Gly-Gly-X (X=Leu, Tyr, Gln) motif in spider dragline silk is not in a β-sheet or α-helix structure and is very likely to be present in a disordered structure with evidence for 31-helix confirmation. In addition, the conformations of the Ala, Ser, and Tyr residues in silk fibroin of B. mori were investigated and it indicates that the Ala, Ser, and Tyr residues are all present in disordered structures in silk I (before spinning), while show different conformations in silk II (after spinning). Specifically, in silk II, the Ala and Tyr residues are present in both disordered structures and β-sheet structures, and the Ser residues are present primarily in β-sheet structures.Dissertation/ThesisDoctoral Dissertation Chemistry 201