Micelle induced dissociation of DNA-ligand complexes: The effect of ligand binding specificity

We investigate the SDS micelle induced dissociation of a small fluorescent ligand 4',6-diamidino-2-phenylindole (DAPI) bound to DNAs of varying sequences. Steady state and time resolved fluorescence measurements affirm minor groove binding of DAPI to poly(dA).poly(dT) and calf thymus DNA while it intercalates in poly(dG).poly(dC). Calorimetric measurements identify the former mode to be entropy driven and the intercalation to be enthalpy driven. Addition of SDS micelles extracts the ligand out of the DNA and relocates it into the micelle independent of the DNA-ligand binding mode. This process is found to be endothermic which is compensated by a huge gain in the entropy. Circular dichroism measurements indicate that the micelles do not affect the structure of DNAs, however, binding and un-binding of DAPI can introduce noticeable alteration in the DNA structure and consequently on the associated hydration which is reflected in solvation measurement. Consideration of a simple two step equilibrium model seems inadequate to account for the observed thermodynamic costs in the dissociation process. The results have been discussed on the basis of an intricate enthalpy-entropy balance.