The interaction of the anticancer agent mitoxantrone with DNA was investigated using microcalorimetry. The results show that the binding of mitoxantrone to DNA was predominantly enthalpy driven with a small but favorable entropic contribution. The equilibrium constant for the binding reaction (mitoxantrone + DNA = mitoxantrone - DNA complex) was calculated to be (5.05 +/- 0.06) . 10(6) M-1 at T = 298.15 K and the binding stoichiometry value show that similar to 2 base pairs were spanned by each mitoxantrone molecule. The equilibrium constant decreased, the standard molar enthalpy change increased and the standard molar entropy change decreased with increasing temperature. However, the change in temperature had little effect on the standard molar Gibbs energy change. The negative value of the standard molar heat capacity change along with enthalpy-entropy compensation behavior suggests the involvement of dominant hydrophobic forces in the binding process. A small but favorable electrostatic component to the binding was revealed from salt dependent calorimetric data and the parsing of the standard molar Gibbs energy change. The binding increased the thermal stability of DNA and the value of the equilibrium constant calculated from the melting data was (6.26 +/- 0.17) . 106 M-1. (C) 2014 Elsevier Ltd. All rights reserved.