Physico-chemical studies of analgesics. The protein-binding of some p-substituted acetanilides

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Abstract
The binding of fifteen p-substituted acetanilides to bovine serum albumin is examined at pH 7·2. An excellent correlation is obtained between the binding enthalpy and Hammett’s substituent constant, s̀. This is interpreted to mean that the binding is non-specific in nature. A very good correlation is also obtained between the entropy of binding and s̀, which suggests that the extent of hydration of unbound drug is a function of the charge separation within the drug molecule. Of the compounds examined, those that have been used clinically as analgesics possess the best thermodynamic properties, being neither so fully bound as to give low free drug concentrations in the bloodstream, nor so little bound that there is no sustained action.