Self-Association of the Penicillin Sodium Nafcillin in Aqueous Solution

Abstract

The self-association of the penicillin drug, sodium nafcillin monohydrate, in aqueous solution has been examined as a function of temperature and electrolyte concentration. Critical concentrations determined by conductivity measurements in water over the temperature range 288.15 to 313.15 K indicated a minimum critical concentration at 303 K. Thermodynamic parameters of aggregation were derived from the critical concentration data using a form of mass action model modified for application to systems of low aggregation number. Values for the enthalpy of aggregate formation Δ calculated by this method showed that the aggregation became increasingly exothermic with increase of temperature. The predicted Δ at 298.15 K was in good agreement with the value determined experimentally by calorimetry. Critical concentrations and the size and effective charge of aggregates were determined in the presence of added electrolyte (0.05−0.40 mol kg-1 NaCl) by static light scattering. The interaction between aggregates was interpreted from diffusion data from dynamic light scattering using the DLVO theory. Changes of 1H NMR chemical shift on aggregation suggested stacking of molecules. Application of mass action theory to the concentration dependence of 1H NMR chemical shifts confirmed the aggregation number from light scattering.