Next Generation Peptide Nucleic Acids for Charge and Spin Transport Studies

PNA is a synthetic analog of DNA in which the sugar diphosphate backbone is replaced by a polyamide one consisting of repeating N-(2-aminoethyl)-glycine (aeg)
units. PNA serves as a good scaffold for organic and inorganic compounds with a variety of magnetic, electronic and photophysical properties and of potential applications.
Though the synthesis of non-modified, aeg-PNA as well as of PNA with modifications in the backbone or nucleobases is relatively straightforward, the synthesis of long modified
PNA strands is time consuming and relatively low yield, and thus costly. Research in this thesis describes the use of the template method for the synthesis of long modified PNAs
and their use in spectroscopic, electronic and magnetic studies. The focus was on the hybridization of short 10-base PNA single strands on a long 20-bp PNA or DNA template
strand to form long PNA duplexes. The 20-bp duplex can be formally seen as the concatenation of two 10-base pair duplexes. The spin-selective transmission of electrons through self-assembled monolayers of stitched y-modified and non-modified PNA duplexes on Au was measured. Variable temperature UV-vis, CD spectroscopy and fluorescence spectroscopy were used to evaluate the stitching protocol for the synthesis of 20-bp PNA duplexes. Self-assembled monolayers (SAMs) of the stitched PNA duplexes with thiol linkers have been characterized by Ellipsometry and PM-IRRAS. The observed spin polarizations for the SAMs of stitched aeg-PNA and y-PNA duplexes were approximately +20% and -5% at room temperature, respectively. This remarkable spin polarization of y-PNAs establishes dsPNA as a candidate for room-temperature spin filter. Scanning tunneling microscope-break junction measurements have been used to examine how the molecular conductance of nucleic acids depends on the chemical nature of their backbone and on the linker group that connects the PNA to the electrodes. The molecular conductance was measured for 10-base pair long homo-duplexes of DNA, aeg- PNA, γ-PNA, and a hetero-duplex of DNA/aeg-PNA; all duplexes had the same sequence
of nucleobases. The molecular conductance was found to vary by 12 to 13 times with the change in backbone. Computational studies showed that the molecular conductance differences between nucleic acids of different backbones correlate with differences in backbone structural flexibility. The molecular conductance was also measured for duplexes connected to the electrode through two different linkers, one directly to the PNA backbone and one directly to the nucleobase stack. The linker caused an order of
magnitude variation in the conductance of a particular duplex. The differences in the electrical conductance due to the chemical nature of the backbone manifested irrespective
of the linker. The highest molecular conductance value, 0.06 G₀, was measured for aeg-PNA duplexes with a base stack linker. These findings reveal an important new strategy
for creating longer and more complex electroactive, nucleic acid assemblies. Finally, the stitching of the short PNA duplexes by coordination to a pair of a ligand (Q or Bpy) situated at adjacent ends of the short PNA strands hybridized on the template was examined. The stability and helical structure of the stitched duplexes in the absence of a metal and in the presence of a metal (Ni²⁺, or Cu²⁺) were determined by variable temperature UV-Vis and CD spectroscopy, respectively. The inclusion of ligands at adjacent ends of two 10-base PNAs hybridized to a template had a very small effect on the stability of the stitched duplex. In contrast, the metal coordination increased the thermal stability of ligand-modified stitched PNA duplexes thus supporting the idea that the inter-strand metal complexes act as glue for the two short PNAs. UV titrations show that the bridging metal complexes have an ML₂ stoichiometry. In one case, the metal complex formed in the middle of the duplex affected the handedness of the stitched duplex. The stability constants of these complexes are similar to those which in past research have been formed between ligands situated in complementary position in the duplexes and acted as alternative base pair.