Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator

A novel naphthalene diimde analogue (NDI) equipped at the imide positions with two guanidinio-carbonyl-pyrrole (GCP) pendant arms interacted significantly stronger with ds-DNA at pH 5 than at pH 7, due to reversible protonation of the GCP arms. This was consequence of a pH-switchable threading intercalation into ds-DNAs only at pH 5, while at neutral conditions (pH 7) NDI-GCP₂ switched to the DNA minor groove binding. Intriguingly, NDI-GCP₂ was at both pH values studied bound to the ds-RNA major groove, still showing a higher affinity and thermal denaturation effect at pH 5 due to GCP protonation. At excess over the DNA/RNA conjugate NDI-GCP₂ showed also aggregation along the ds-polynucleotide and AFM and DLS demonstrated that NDI-GCP₂ has pronounced ds-DNA condensation ability.