Microcalorimetric Investigation of the Binding of Some Chemotherapeutic Agents and Related Molecules to Calf Thymus DNA

Batch microcalorimetry was used to estimate directly the standard enthalpies of the binding of small molecules to DNA. These values were compared with those obtained from spectrophotometric binding constants and van't Hoff plots. The close agreement between the independently obtained enthalpies indicates that the appropriate (best) binding model has four phosphates per binding site. Thermodynamic binding constants were obtained from apparent binding constants measured at different ionic strengths. From these and the measured standard enthalpies, standard free energies and standard entropies of binding were calculated. The weak, presumably external, binding alleged to occur at high formal molar concentration ratios of ligand to DNA bases could not be detected by a measurable heat of binding.