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

Poulami Jana,Ivo Piantanida,Carsten Schmuck,Filip Šupljika

doi:10.3762/bjoc.16.185

Abstract

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.

Highlights

The small molecules non-covalently binding to DNA or RNA are essential for life as we know it, and it was not surprising that a huge number of synthetic small molecules has been prepared and studied for broad biochemical and biomedical applications [1,2]
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
We designed and synthesized a novel naphtalene diimide analogue equipped at imide positions with two guanidinio-carbonyl-pyrrole (GCP) pendant arms

Summary

Introduction

The small molecules non-covalently binding to DNA or RNA are essential for life as we know it, and it was not surprising that a huge number of synthetic small molecules has been prepared and studied for broad biochemical and biomedical applications [1,2]. In this work we focused our attention to a less common DNA/RNA binding motif: threading intercalation This sterically very demanding binding mode is characterised by a central large aromatic moiety, in this case the wellknown naphthalene diimide (NDI), equipped at both sides of the long axis with large substituents, which have to thread through DNA double helix and are positioned in the minor and major groove, respectively [23,24,25]. Since GCP units always interact within DNA/RNA grooves, our particular interest in threading intercalation is the positioning of side chains simultaneously in both, the minor and major groove; in that way allowing two GCP units different recognition environment and eventually better sensing of ds-polynucleotide secondary structures. For comparison between double-stranded (ds) DNA and ds-RNA, poly(rA)–poly(rU) was chosen as an A-helical structure having a major groove convenient for binding of bulky small molecules

Results and Discussion

Conclusion

Synthetic procedures