Thermodynamics of the induction of self-structure in polyadenylic acid by the cytotoxic isoquinoline alkaloid coralyne was investigated using calorimetry tools. The binding was an exothermic process driven by large negative enthalpy change. The equilibrium constant at [K+]=(130±0.01)mM and T=(298.15±0.01)K was calculated to be (1.34±0.07)·106M−1. Temperature dependent calorimetric studies suggested weakening of the self-structure at higher temperatures. The self-structure induction process was characterized by complete enthalpy-entropy compensation. The temperature dependence of the enthalpy change yielded negative heat capacity value. The equilibrium constant decreased with increasing [K+] apparently due to the weakening of the self-structure at higher salt concentrations. Differential scanning calorimetry studies testified for the formation of self-structure in (50±0.01)–(130±0.01)mM [K+]. Parsing of the standard molar Gibbs energy change revealed that the non-polyelectrolytic forces dominated the self-structure induction process.