Metal binding to peptide nucleic acids modified with 8-hydroxyquinoline or 2,2'-bipyridine

The research presented in this dissertation is focused on the incorporation of 8-hydroxyquinoline and 2,2'-bipyridine in peptide nucleic acid oligomers and duplexes, which then that act as binding sites for metal ions. The properties of these hybrid inorganic-nucleic acids rely on several important factors including the stability of the modified nucleic acid structure and the effect on it of metal ion binding. Of great importance for potential applications is the ability of modified duplexes to bind specific metal ions in predefined positions within the nucleic acid scaffold.;EPR studies on a PNA duplex containing two side-by-side 8-hydroxyquinoline ligands (Q) in the presence of Cu2+ demonstrated that a square-planar complex was formed in the center of the duplex. UV-Visible thermal denaturation studies and CD spectroscopy confirmed that the metal containing duplex had high thermodynamic stability and a helical structure.;Spectrophotometric titrations and EPR spectroscopy were used to investigate Cu2+ and Ni2+ complexes formed with PNA oligomers and duplexes containing one or more bipyridine (B) modifications. One finding from this study was that a duplex that incorporates a B pair in the center of the duplex is less stable in the presence of Ni2+ than one that contains the same pair near the end of the duplex, which suggests that the incorporation of metal-complexes may be used as a means to create duplexes that do not fray at the ends. Incorporation of multiple, adjacent ligand modifications in PNA oligomers resulted in PNA duplexes that contained metal complexes with various coordination numbers and geometries, depending on the ligand, the metal, and the metal-to-PNA ratio in the solution.;Spectrophotometric titrations of duplexes containing two or three Q ligands in adjacent positions in the center of a duplex were shown to bind stoichiometric ratios of Cue, forming two or three Cu(Q) 2 complexes in each duplex. UV melting curves of the modified duplexes showed increasing melting temperature with increasing concentrations of Cu 2+ present, up to a 1:2 Cu2+:Q ratio, which is attributable to the formation of multiple neutral, inter-stand Cu( Q)2 complexes. EPR spectra for these duplexes in the presence of 1:2 Cu2+:Q suggest that electronic and magnetic interactions exist between the metal ions, a property which is very important in the design of novel functional devices based on metal-containing PNA duplexes, and which may also play a role in electron transfer though PNA duplexes mediated by metal ions.;The significant difference in the binding constants of B and Q for Cu+ and Cu2+ was exploited in the development of a PNA duplex that contained both ligands in different positions. Oxidation and reduction of copper resulted in translocation of the metal from one binding site to the other, and is the first example of a redox-driven molecular switch incorporated in a nucleic acid duplex. These studies have demonstrated the versatility and potential of ligand-modified PNA for use as building blocks for molecular devices and structures.