The interaction of calf thymus DNA with [pyridine dianline](2)[Co(phenanthroline dicarboxylate)(2)], [pyda](2)[Co(phendc)(2)], complex has been studied at 10 mM phosphate buffer at 27 degrees C, pH 7.0 using various techniques including isothermal titration calorimetry (ITC), UV-vis spectrophotometry and potentiometric titration. Sigmoidal absorption profile implies the existence of cooperative interactions between DNA and [pyda](2)[Co(phendc)(2)] that induces a conformational change in DNA structure. Scatchard plots confirm this cooperative interaction. The calorimetric enthalpy curve of [pyda](2)[Co(phendc)(2)] upon interaction with DNA is measured by ITC. The enthalpy of binding (Delta H-bin) of [pyda](2)[Co(phendc)(2)] with DNA is also obtained spectrophotometrically by determining of equilibrium binding constants at 27 and 37 degrees C based on Wyman binding potential and van't Hoff relation. The enthalpy of ionization (Delta H-ion) is also obtained by acid-base titration at 27 and 37 degrees C in 100 mM KCl solution using modified differential van't Hoff relation for estimation of (Delta H-ion). The binding data was analyzed in a two-set binding sites model based on the Hill equation. The first phase of the calorimetric enthalpy curve is consistent with a first set of binding sites and further phases are consistent with a second set of binding sites. (c) 2004 Elsevier B.V. All rights reserved.