A Cu(I) complex groove binder with a high affinity towards DNA denaturation

The interaction of ligands with double-stranded DNA is important for many intracellular processes. We demonstrate the ability of a copper(I) bis-triphenylphosphine based complex with a high affinity for target DNA via a minor groove binding mode. The fluorescence and UV–visible results show that a complex-DNA conjugate forms in the ground state with a binding affinity in order of 10+5 M−1. According to the findings of competitive fluorescence experiments, the phosphine substituent attaches in the minor groove of DNA by replacing Hoechst molecules at A-T rich regions. Also, relatively small changes in the CD spectrum of DNA as well as in its viscosity indicated that the Cu(I) complex could interact as a groove binder. The resulted entropy and enthalpy changes denoting the Van der Waals forces as the key binding mechanism in the interaction. Fluorescent DNA melting analysis shows that the Cu(I) complex is strongly disturbed the stability of the DNA base pairs, making the dsDNA to ssDNA easier to transition. The insertion of phosphine bulky substituents in the DNA minor groove was approved by docking analysis. Moreover, the molecular dynamic simulation shows an opening of DNA chains due to the Cu(I) complex force applied.