Supramolecular structures based on peptide nucleic acids and transition metal ions.

摘要

The research presented in this dissertation is focused on the incorporation of 2,2';6',2"-terpyridine in peptide nucleic acid duplexes and 2,2'-bipyridine and hydroxamate based ligands in peptide nucleic acid triplexes. These ligands act as binding sites for specific metal ions in predefined positions within the nucleic acid scaffold leading to the formation of hybrid inorganic-nucleic acids. In addition, an important part of this research is dedicated to chiral induction in the PNA helixes and the study of the changes in structural conformation of PNA helixes upon metal binding.;The significant difference in the binding constants of 2,2'-bipyridine and hydroxamate ligands for Fe2+ and Fe3+ was exploited in the development of a PNA triplex that contained both ligands in different positions. Modification of a PNA triplex with both ligands showed large destabilization and additions of iron ions partially restored the stability of the triplex. Oxidation and reduction of iron resulted in translocation of the metal from one binding site to the other. These studies have demonstrated the versatility and potential of ligand-modified PNA for use as building blocks for molecular devices and structures.;The effect of a central nucleobase X in a 7-mer ssPNA or a XY bp a 7bp dsPNA on charge transfer properties of single and double stranded PNA of T 3-X-T3 and (TA)3(XY)-(TA)3 type was investigated using cyclic voltammetry and MD simulations. Both experiments indicated that the charge transfer constant and the average conductance in ssPNA decreases in the order T3-G-T3 > T3-A-T 3 > T3-C-T3 = T3-T-T3 and in the dsPNA (TA)3-(GC)-(TA)3 ∼ (TA)3-(CG)-(TA) 3 > (TA)3-(AT)-(TA)3 ∼ (TA) 3-(TA)-(TA)3. The charge transfer rate constant is much higher for the dsPNA than for the ssPNA. The charge transfer through the ssPNA occurs by hole-mediated superexchange mechanism and in dsPNA through a mixed mechanism as a transition between pure superexchange and hopping regimes.;The 2,2;6',2"-terpyridine was attached via a linker to the gamma-modified Aeg backbone and formed L-Tpy PNA monomer, which was found to induce strong right- handed effect into the dsPNA. Its interaction with Cu2+ provided information about the position of the metal complex with respect to the PNA duplex. For example, when the [Cu(Tpy)2] 2+ complex was formed within the duplex, the chiral effect was intact, remaining right-handed due to the effect induced by L-Tpy PNA monomer; when the [Cu(Tpy)2]2+ complex was formed in a cross-over manner between the duplexes, there was a switch in chirality from right-handed to left-handed helixes. EPR studies on the PNA duplexes containing [Cu(Tpy)2]2+ complex demonstrated that an octahedral complex was formed whether in the center or in the terminal position of the duplex. UV-Visible thermal denaturation studies confirmed that the metal containing duplex had high thermodynamic stability.