Supramolecular association of a diguanidine derivative with a porphyrin-cyclodextrin conjugate and its binding to G-Quadruplex DNA

Abstract

G-quadruplex-selective small molecule binders are synthesized as they find relevance in therapeutic intervention. This article reports a new and novel diguanidine derivative containing benzimidazole moiety. The synthesized compound is characterized using spectroscopic techniques. An inclusion complex of the compound with a porphyrin-tethered β-cyclodextrin where the latter acts as a host molecule. The structure of the complex is optimized by employing a rotating-frame Overhauser effect spectroscopy. Two host molecules encapsulate the diguanidine forming a 1:2 complex, as evidenced by the spectral analysis. The compound and its inclusion complex are analyzed for their binding to duplex and G-quadruplex DNAs viz., kit22, myc22, and telo. The binding constants are derived using fluorescence spectroscopic titrations. The diguanide derivative: porphyrin-cyclodextrin complex shows stronger binding to the quadruplexes than the duplex DNA, with the binding constant values of (8.20 ± 0.51) × 105, (2.40 ± 0.28) × 106, and (8.20 ± 0.10) × 105 M−1 for the interaction with kit22, myc22, and telo, respectively. The complexed form of diguanidine shows a greater affinity for myc22 than the other G-quadruplexes and duplex DNA. Circular dichroism spectra are recorded to further analyze conformational alterations on the binding interaction. The binding characteristics of the ligands against various DNAs are discussed in detail.