Metal Binding to Bipyridine-Modified PNA

Abstract

Substitution of natural nucleobases in PNA oligomers with ligands is a strategy for directing metal ion incorporation to specific locations within a PNA duplex. In this study, we have synthesized PNA oligomers that contain up to three adjacent bipyridine ligands and examined the interaction with Ni2+ and Cu2+ of these oligomers and of duplexes formed from them. Variable-temperature UV spectroscopy showed that duplexes containing one terminal pair of bipyridine ligands are more stable upon metal binding than their nonmodified counterparts. While binding of one metal ion to duplexes that contain two adjacent bipyridine pairs makes the duplexes more stable, additional metal ions lower the duplex stability, with electrostatic repulsions being, most likely, an important contributor to the destabilization. UV titrations showed that the presence of several bipyridine ligands in close proximity of each other in PNA oligomers exerts a chelate effect. A supramolecular chelate effect occurs when several bipyridines are brought next to each other by hybridization of PNA duplexes. EPR spectroscopy studies indicate that even when two Cu2+ ions coordinate to a PNA duplex in which two bipyridine pairs are next to each other, the two metal-ligand complexes that form in the duplex are far enough from each other that the dipolar coupling is very weak. EXAFS and XANES show that the Ni2+-bipyridine bond lengths are typical for [Ni(bipy)2]2+ and [Ni(bipy)3]2+ complexes.

Metal-containing peptide nucleic acid conjugates

“…147 However, the incorporation of multiple M 2+ -bipy moieties in the centre of a PNA duplex did not grant greater thermal stability, probably because of electrostatic and steric interactions between adjacent, positively charged complexes. 147 Moreover, UV titrations showed that the presence of several bipy ligands in close proximity to each other in PNA oligomers exerts a chelate effect, which favours the formation of complexes in which the metal ion coordinates the maximum number of accessible ligands. 147 It is noteworthy that the melting temperatures did not change in the presence of 148 In the case of 11-containing PNA oligomers, Achim et al showed by variable-temperature UV-vis spectroscopy that, in the presence of Cu 2+ , duplexes were formed even from 11-containing strands that have a large number of mismatches.…”

“…147 With this in mind, Achim and co-workers have inserted up to three consecutive 8-hydroxyquinoline-(11, Figure 14) or bipyridine (bipy)-modified (12, Figure 14) PNA monomers into PNA oligomers. [147][148][149][150] They then examined in detail the interaction of these oligomers with different metal ions and also the stability of duplexes formed from them. In the case of 12, variable-temperature UV spectroscopy showed that duplexes containing one terminal pair of bipyridine ligands are more stable upon metal binding with Ni 2+ and Cu 2+ than their non-modified counterparts.…”

“…In the case of 12, variable-temperature UV spectroscopy showed that duplexes containing one terminal pair of bipyridine ligands are more stable upon metal binding with Ni 2+ and Cu 2+ than their non-modified counterparts. 147 The introduction of a ligand pair situated near the centre of a PNA duplex significantly decreased the duplex's stability in contrast to a modification near the end of the duplex. 147 Furthermore, the stabilization exerted by metal ions on terminally modified duplexes surpassed the stabilization of duplexes with a central modification.…”

“…147 Furthermore, the stabilization exerted by metal ions on terminally modified duplexes surpassed the stabilization of duplexes with a central modification. 147 This difference is the consequence of the base pairs at the end of the duplex being subject to fraying. 147 The metal-ligand bonds reduce the fraying and significantly stabilize the duplex.…”

“…147 This difference is the consequence of the base pairs at the end of the duplex being subject to fraying. 147 The metal-ligand bonds reduce the fraying and significantly stabilize the duplex. 147 However, the incorporation of multiple M 2+ -bipy moieties in the centre of a PNA duplex did not grant greater thermal stability, probably because of electrostatic and steric interactions between adjacent, positively charged complexes.…”