The effect of electron-withdrawing groups on the binding properties of bisphenol A to DNA: Insights from multi-spectral, electrochemical, and molecular docking

Bisphenol A is a hormone that contributes to the normal development of organisms. In this study, the structure-affinity relationship between bisphenol A and DNA was analyzed using calf thymus DNA as a biomacromolecule model. The influence of space volume and substituent effects on the interactions were investigated by fluorescence spectroscopy, viscosity measurements, circular dichroism spectroscopy, electrochemical tests and molecular simulations. The experimental findings demonstrated that adding electron-withdrawing groups increased the space volume on both sides of bisphenol A, limiting its insertion in DNA base pairs. Circular dichroism studies revealed that electron-withdrawing derivatives did not affect the base accumulation ability of DNA. The electrochemical measurements described a positive correlation between the substituents’ electron-withdrawing and the enhancement in interactions between bisphenol A and calf thymus DNA. Experimental results were further validated through molecular simulations. These findings provide crucial information for the structural modification of bisphenol A through space volume and substituent effects.