Thermodynamical model of mixed aggregation of ligands with caffeine in aqueous solution. Part II

Abstract

A statistical–thermodynamical model of mixed association in which one component’s self-association is unlimited while the second component does not self-aggregate is described. The model was tested with 4′,6-diamidino-2-phenylindole-dihydrochloride (DAPI) and ethidium bromide (EB) using light absorption spectroscopy and calorimetry. The system is controlled by two parameters, which represent self-aggregation ‘neighborhood’ association constant K CC and mixed ‘neighborhood’ association constant K AC . Calculated, using this model, K AC =58.2±1 M −1, K AC =64.6±2 M −1 for DAPI and EB, respectively, are in good agreement with known values of stacking interactions. The titration microcalorimetric measurement of DAPI–CAF interaction Δ H=−11.1±0.4 kcal/mol is also consistent with this type of reaction. The structures of the stacking complexes were also confirmed by semi-empirical molecular modeling in the presence of water. The data indicate that CAF forms stacking complexes with DAPI and EB, thus effectively lowering the concentration of the free ligands in the solution, and therefore, CAF can be used to modulate aromatic compound activity.