Spectroscopy driven DFT computation for a structure of the monomeric Cu2+-Curcumin complex and thermodynamics driven evaluation of its binding to DNA: Pseudo-binding of Curcumin to DNA
Tanmoy Saha, Soumen Singh, Sanjay Kumar, Saurabh Das
Journal of Molecular Structure
In an attempt to overcome limitations of Curcumin from being an important molecule in biology and medicine, a monomeric complex of CuII [Cu(Cur)(OCOCH3)(H2O)] was prepared. Physico-chemical studies in solution using copper acetate and Curcumin indicate formation of a 1:2 CuII:Curcumin species. However, attempts to prepare it always led to the formation of a 1:1 CuII:Curcumin species, if CuII-acetate was used as the starting material. In the absence of a single crystal or an appropriate powder X ray diffraction data that would allow solving of the structure, it was arrived at by spectroscopy guided DFT calculations. Unlike Curcumin, the prepared complex was stable under physiological conditions, an advance achieved through complex formation. Effective binding of the complex to DNA with an ability to enhance cellular uptake owing to the presence of CuII are other benefits of complex formation that might increase its cytotoxic potential. The complex has a reasonably strong affinity for DNA realized from binding constant values obtained with calf thymus DNA at different temperatures in the range 25 °C–35 °C. This enabled an evaluation of thermodynamic parameters (ΔH, ΔS and ΔG), that helped in determining the mode of binding between the complex and DNA as realized from a correlation of thermodynamic signatures to binding types. The study may be considered a case of pseudo-binding of Curcumin to DNA since the complex containing a Curcumin bound the metal ion does not dissociate in solution under physiological conditions, i.e. remains as one unit. Hence binding of the complex to DNA is also the binding of Curcumin to it present as one “single unit”, a major advancement based on a biophysical approach. Besides, aspects like stability of the complex in solution, prevention of degradation of Curcumin in aqueous buffer or biological milieu, binding with mammalian DNA are other aspects that are significant for use of the complex on biological targets.
Absorption, DNA structure, Ligand binding, Circular dichroism, Biochemistry