Biophysical and electrochemical studies on the interaction of arbutin drug with calf-thymus DNA

Understanding the interaction of therapeutic drugs with DNA is crucial for designing highly selective DNA-targeted medicines that could overcome the current therapeutic limitations. In this endeavour, the DNA binding behaviour of arbutin (<b>ATN</b>) was explored using multi-spectroscopic, electrochemical and computational studies. The UV-Vis spectral studies authenticated the complexation of <b>ATN</b> with CT-DNA and exposed <b>ATN</b> as a moderately strong DNA binder with a binding constant of 8.029 × 10³ M⁻¹. The findings of fluorescence spectral studies not only revealed the spontaneous ground state complex formation between <b>ATN</b> and CT-DNA, but also emphasised the role of hydrogen bonding and Van der Waals interactions in stabilising the <b>ATN</b>/CT-DNA complex. Since the competitive dye displacement assay strongly excluded the plausibility of classical intercalation and conventional groove binding mode of <b>ATN</b>, viscosity studies provided clues regarding the external binding mode of <b>ATN</b>. The appreciable enhancement resulted in the fluorescence emission of the <b>ATN</b>/CT-DNA complex upon increasing NaCl concentration, which certified <b>ATN</b> as an external binder. The CD spectral results exposed the <b>ATN</b>-induced moderate conformational alterations in CT-DNA. Remarkably, the voltammetric titration results labelled the glucopyranoside moiety of <b>ATN</b> as a DNA binding unit with a formation constant of 2.57 × 10⁴ M⁻¹ rather than the hydroquinone moiety of <b>ATN</b>. Molecular docking and metadynamics simulation outcomes served as pictorial evidence of experimental results. They revealed the predominant contribution of hydrogen bonding interactions in stabilising <b>ATN</b>/DNA complexation.