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 ≤ X₂ ≤ 0.5, where X₂ is the mole fraction of LC in the mixture, while they decreased rapidly with increasing m_t at 0.5 < X₂ < 1. It was shown from the pH measurements that almost all LC molecules were changed into LC•H⁺ ions by protonation at 0 < X₂ ≤ 0.5 and both forms coexisted only at 0.5 < X₂ ≤ 1. The quantities of the respective LC and LC•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•H⁺ existed in the adsorbed film at the coexisting composition. The partitioning behavior of LC and LC•H⁺ in the adsorbed film was characterized by three composition regions: (1) slight partitioning of low surface-active LC•H⁺ in the region at 0 ≤ X₂ < 0.5, (2) preferential partitioning of LC at 0.5 < X₂ < around 0.7, and (3) negative partitioning of LC•H⁺ at around 0.7 ≤ X₂ < 1. The present results clearly indicate that uncharged local anesthetics transfer into hydrophobic environments such as cell membranes more than charged ones.