Chemical and thermal denaturation of calf thymus DNA (as a multidomain macromolecule) have been investigated in the presence of high concentrations of dimethyltin dichloride (Me 2 SnCl 2 ) 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, Me 2 SnCl 2 is a chemical denaturant and denatures the doublestrand DNA in a three-state manner. The denaturation data are analyzed based on the effective Gibbs free energy (DG°e ff ) approach and the chemical denaturation parameters including DG°e ff , 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 (DH°m) and binding enthalpy (DH°b). Furthermore, at low concentrations (up to 5 mM), Me 2 SnCl 2 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 Me 2 SnCl 2 (more than 9 mM) caused considerable destabilization of DNA associated with the formation of a partially unfolded intermediate at 13.6 mM of Me 2 SnCl 2 . 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 (Me 2 SnCl 2 ) concentration (0-16 mM).
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