DNA-binding studies of a new Cu(II) complex containing reverse transcriptase inhibitor and anti-HIV drug zalcitabine

Abstract

In this study, a new copper(II) complex with zalcitabine (ddC) drug was synthesized and characterized by Fourier-transform infrared spectroscopy (FT-IR), ultraviolet–visible spectroscopy (UV–vis), mass spectroscopy, thermal gravimetric analysis and density functional theory. Then, its effect on calf-thymus DNA (CT-DNA) was investigated using absorption and fluorescence spectroscopy and viscometry technique. On the basis of FT-IR and computational studies, zalcitabine chelates with copper using its C(2)=O and N(3) group in the [Cu(zalcitabine)Cl₂] ([CuCl₂(ddC)]) complex. On the basis of the electrospray ionization mass spectroscopy of the Cu–ddC complex, monomeric copper complex [C₉H₁₃N₃O₃CuCl₂] was formed. The results of fluorescence studies indicated increasing to around 2.5 times in emission intensity of fluorescence signal of the complex. The enhancement of emission intensity and also the positive ΔH and positive ΔS values suggested that the hydrophobic interaction plays a major role in the binding with overall binding constant of 1(±0.25)×10⁵ M⁻¹. The ΔG value implied that the interaction occurred between DNA and the complex formation was spontaneous. Finally, changes in the relative viscosity showed that groove binding must be the predominant form of binding. Evidences are provided that [Cu(ddC)Cl₂] could interact with DNA via minor groove interaction mode.

Keywords:

• Anti-HIV drug
• zalcitabine
• copper complex
• hydrophobic interaction
• groove-binding

Acknowledgements

Financial support from the Razi University Research Center, Medical Biology Research Center (MBRC), and the Research Center of Oils and Fats, Kermanshah University of Medical Sciences is gratefully acknowledged.