Electrostatic contributions to cyanine dye aggregation on peptide nucleic acid templates

A symmetrical benzothiazole-based dicarbocyanine dye with anionic propylsulfonate substituents was synthesized in order to assess the importance of electrostatic forces in the assembly of helical dye aggregates on peptide nucleic acid (PNA) templates (Smith, J. O.; Olson, D. A.; Armitage, B. A. J. Am. Chem. Soc. 1999, 121, 2686-2695). UV-vis and circular dichroism spectroscopy demonstrate effective aggregation of the dye on a 10 base pair PNA-PNA duplex but weak aggregation on the analogous PNA-DNA duplex. The CD spectra are consistent with a left-handed helical morphology for the dye aggregate, as expected for the left-handed PNA-PNA double helical template. Continuous variations analysis indicates formation of a 6:1 aggregate of the dye on a 10 base pair PNA-PNA duplex. An analogous dye bearing two cationic side chains and a net charge of +3 does not aggregate on the PNA-PNA duplex but can be recruited into a mixed aggregate with the anionic dye due to partial charge neutralization. Finally, charged groups at the termini of the duplex affect both the stability and chirality of the dye aggregate, with cationic (L)-lysine residues promoting formation of stable, left-handed helical aggregates, while anionic (L)-glutamate residues lead to less stable, right-handed helical aggregates.