Stability of DNA upon interaction with dimethyltin dichloride

Abstract

Chemical and thermal denaturation of calf thymus DNA (as a multidomain macromolecule) have been investigated in the presence of high concentrations of dimethyltin dichloride (Me2SnCl2) over the temperature range (55–95°C) in 50.0 mM phosphate buffer at pH 7.6 using temperature scanning spectroscopy and calorimetry methods. Results showed that over the concentration range of 6–16 mM, Me2SnCl2 is a chemical denaturant and denatures the double-strand DNA in a three-state manner. The denaturation data are analyzed based on the effective Gibbs free energy (ΔG°eff) approach and the chemical denaturation parameters including ΔG°eff, m value and equilibrium unfolding constant (K U) were obtained. Ultraviolet (UV) melting curves of the DNA at 260 nm as well as the calorimetric measurements were used to estimate the binding constants (K), melting enthalpy (ΔH°m) and binding enthalpy (ΔH°b). Furthermore, at low concentrations (up to 5 mM), Me2SnCl2 binds to the phosphate groups of DNA in an exothermic step and had no significant effect on double-strand DNA stability, confirmed by the fact that the T m value did not change. However, high (denaturing) concentrations of Me2SnCl2 (more than 9 mM) caused considerable destabilization of DNA associated with the formation of a partially unfolded intermediate at 13.6 mM of Me2SnCl2. The formed intermediate showed a lower thermal transition temperature (T m) by a magnitude of 10°C in relation to the native DNA. Finally, a new correlation is introduced for interpretation of thermal denaturation behavior of calf thymus DNA over the whole range of ligand (Me2SnCl2) concentration (0–16 mM).