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 (ATN) was explored using multi-spectroscopic, electrochemical and computational studies. The UV-Vis spectral studies authenticated the complexation of ATN with CT-DNA and exposed ATN 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 ATN and CT-DNA, but also emphasised the role of hydrogen bonding and Van der Waals interactions in stabilising the ATN/CT-DNA complex. Since the competitive dye displacement assay strongly excluded the plausibility of classical intercalation and conventional groove binding mode of ATN, viscosity studies provided clues regarding the external binding mode of ATN. The appreciable enhancement resulted in the fluorescence emission of the ATN/CT-DNA complex upon increasing NaCl concentration, which certified ATN as an external binder. The CD spectral results exposed the ATN-induced moderate conformational alterations in CT-DNA. Remarkably, the voltammetric titration results labelled the glucopyranoside moiety of ATN as a DNA binding unit with a formation constant of 2.57 × 10⁴ M^-1 rather than the hydroquinone moiety of ATN. Molecular docking and metadynamics simulation outcomes served as pictorial evidence of experimental results. They revealed the predominant contribution of hydrogen bonding interactions in stabilising ATN/DNA complexation.