Typescript. / Thesis (Ph. D.)--University of Hawaii at Manoa, 1984. / Includes bibliographical references. / Microfiche. / x, 216 leaves, bound ill. 29 cm

The origin of the first RNA polymers is central to most current theories regarding the origin of life. However, difficulties associated with the prebiotic formation of RNA have lead many researchers to conclude that simpler polymers, or proto-RNAs, preceded RNA. These earlier polymers would have been replaced by RNA over the course of evolution. A remaining difficulty for this theory is that the de novo synthesis of a feasible proto-RNA has not yet been demonstrated by plausible prebiotic reactions. This thesis focuses on two problems associated with prebiotic proto-RNA synthesis: The formation of nucleosides and the necessity of reversible backbone linkages for error correction in nucleic acid polymers. "The Nucleoside Problem", or the lack of success in forming pyrimidine nucleosides by plausible prebiotic reactions, represents a significant stumbling block to the RNA world hypothesis. Nearly four decades ago Orgel and coworkers demonstrated that the purine nucleosides adenosine and inosine are synthesized by heating and drying their respective bases and ribose in the presence of magnesium, but these reaction conditions do not yield the pyrimidine nucleosides uridine or cytidine from their respective bases. In this thesis a potential solution to The Nucleoside Problem is hypothesized based upon a proposed chemical mechanism for nucleoside formation. This hypothesis is supported by the successful synthesis of 2-pyrimidinone nucleosides by a plausible prebiotic reaction in good yield, demonstrating that pyrimidine nucleosides could have been available in the prebiotic chemical inventory, but that uridine and cytidine were likely not abundant. Reversible backbone linkages are necessary to provide a mechanism for error correction in non-enzymatic template-directed syntheses of proto-RNAs. In this thesis, acetals are explored as low-energy, reversible linkage groups for nucleosides in polymers. The synthesis of glyoxylate-acetal nucleic acids (gaNAs) through simple heating-drying reactions from neutral aqueous solutions is demonstrated, and these linkages are shown to be hydrolytically stable under a considerable range of solution conditions. Computational models demonstrate that the glyoxylate linkage is an excellent electronic and isosteric replacement for phosphate. Molecular dynamics simulations also indicate that a gaNA duplex would have structural properties that closely match a phosphate-linked RNA helix, suggesting the possibility for cross-pairing between gaNAs and RNAs, allowing for sequence transfer and genetic continuity through the evolution from proto-RNAs to RNA. The principles illustrated in this thesis by 2-pyrimidinone nucleoside and gaNA synthesis can be extended to other prebiotic condensation reactions. Factors affecting condensation yield, such as thermodynamics, kinetics, reactant solubility, and salt effects, are summarized herein.