Thermodynamic Properties of the Complex Formed by Interaction of Two Anionic Amphiphilic Penicillins with Human Serum Albumin

The partial specific volume and adiabatic compressibility of the complexes formed by the interaction of the amphiphilic penicillins cloxacillin and dicloxacillin with human serum albumin at a concentration of 0.2% w/v in aqueous solution, and at penicillin concentrations below the critical micellar concentration, were obtained from density and sound velocity measurements at temperatures of 15,25, and 35 °C. Increases of the apparent partial specific volumes and adiabatic compressibilities of the drug-protein complexes with drug concentration in the initial stages of drug adsorption have been discussed before in terms of the development of a diffuse double layer around the complex. Subsequent decreases in these quantities after saturation of the protein surface at higher drug concentrations are thought to reflex conformational changes in the protein attributable to a more compacted tertiary structure and a possible onset of premicellar aggregation of drug in solution causing dehydration of the complex because of competition for available free water. Binding isotherms obtained by the application of isothermal titration calorimetry to a study of the adsorption process at 25 °C have provided support for these conclusions.