The role of both intercalation and groove binding at AT-rich DNA regions in the interaction process of a dinuclear Cu(I) complex probed by spectroscopic and simulation analysis.

[Display omitted] • The binding mechanism of a dinuclear Cu(I) complex to DNA helix was investigated. • Both groove binding and intercalation modes were observed. • The Cu(I) complex was preferentially bind to AT-rich DNA regions. • The van der Walls and hydrophobic forces stabilized the Cu(I) complex-DNA conjugate. • The Cu(I) complex showed cytotoxicity effect on MCF-7 cell line more than cisplatin. In this research paper, the synthesis process and characterization of a dinuclear Cu(I) phosphine complex, as well as spectroscopic and simulation analysis of its interaction with DNA helix, are presented. The monoclinic phase [Cu(PPh 3)(L 0.5)(I)] 2 with a tetrahedral molecular geometry was elucidated based on X-ray single-crystal diffraction data. The significant association constant (6.88 × 105) and remarkable hyperchromism as obtained from UV–Visible spectra indicated a high binding affinity of the Cu(I) complex for DNA, which is in accordance with both intercalation and groove binding modes. The results of competitive fluorescence experiments along with molecular docking simulation proved that the planar part of the complex can insert into the core of adenine nucleobases and compete with methylene blue for the intercalative binding sites, while the bulky substituent binds in the minor groove of DNA via replacement of Hoechst molecules at A-T rich regions. According to thermodynamic parameters (the negative values of ΔH° and ΔS°), it is quite clear that the interaction process is enthalpy-favored while disfavored by entropy and van der Walls and hydrophobic forces play a major role in stabilization of right-handed B-DNA form during the interaction, as shown in the circular dichroism spectra. Based on the above findings partial intercalation mode at A-T rich region of DNA was proposed. The cytotoxicity and apoptosis results on MCF-7 cell line indicated positive effect of the Cu(I) complex in controlling growth and viability of breast cancer more than cisplatin. [ABSTRACT FROM AUTHOR]