Dissociation equilibrium between uncharged and charged local anesthetic lidocaine in a surface-adsorbed film

The dissociation equilibrium between uncharged local anesthetic lidocaine (LC) and charged local anesthetic LC (LC . H+) in a surface-adsorbed film was investigated by measuring the surface tension and pH of aqueous solutions of a mixture of hydrochloric acid and LC. The surface tension values decreased slightly with increasing total molality m(t) at 0 less than or equal to X-2 less than or equal to 0.5, where X-2 is the mole fraction of LC in the mixture, while they decreased rapidly with increasing mt at 0.5< X-2 <= 1. It was shown from the pH measurements that almost all LC molecules were changed into LC center dot H+ ions by protonation at 0 < X-2 less than or equal to 0.5 and both forms coexisted only at 0.5< X-2 <= 1. The quantities of the respective LC and LC center dot H+ transferred from the aqueous solution to the adsorbed film, i.e., their surface densities, were calculated by applying the thermodynamic equations derived to the surface tension and pH data. A greater quantity of LC than LC center dot H+ existed in the adsorbed film at the coexisting composition. The partitioning behavior of LC and LC center dot H+ in the adsorbed film was characterized by three composition regions: ( 1) slight partitioning of low surface-active LC center dot H+ in the region at 0 <= X-2 <= 0.5, (2) preferential partitioning of LC at 0.5< X-2< around 0.7, and ( 3) negative partitioning of LC center dot H+ at around 0.7 <= X-2 <= 1. The present results clearly indicate that uncharged local anesthetics transfer into hydrophobic environments such as cell membranes more than charged ones.