G-quadruplex binding affinity variation on molecular encapsulation of ligands by porphyrin-tethered cyclodextrin

[Display omitted] •Three structurally similar guanidinobenzimidazoles are synthesized.•There is affinity differences of the ligands for the duplex DNA and the G-quadruplexes.•A modified cyclodextrin forms inclusion complexes with the guanidinobenzimidazoles.•A bromo-substituted compound shows the greatest affinity for the quadruplex kit22. Non-canonical nuclei acid forms exist in the genome and are widely involved in the control of biological processes. Guanine-rich nucleic acid sequences can form non-canonical DNA forms known as G-quadruplexes. They have become molecular targets in cancer therapy. The structural differences of DNA-binding molecules lead to the alteration of binding affinities for G-quadruplexes. In this article, we present the synthesis and characterization of a series of benzimidazole derivatives. In addition, inclusion complexes of the compounds are made with a porphyrin-β-CD derivative. 2D ROESY spectra provide evidence of the structure of the inclusion complexes. The binding interaction of the benzimidazoles and the inclusion complexes with double-stranded and three G-quadruplex DNAs are studied employing spectroscopic techniques. An order 10⁶–107 M−1 is observed as binding strengths in particular cases. The G-quadruplex selectivity is discussed based on the binding constants. The bromo- substituted compound shows a greater affinity for G-quadruplexes over the duplex DNA, showing a high G-quadruplex selectivity. It indicates the structural dependence of the ligand on the strength of binding to quadruplex DNAs. Further, circular dichroism is utilized to extend insight into the interaction of the strong-binding compound with the duplex and G-quadruplex DNAs.