Solubilization sites and acid-base forms of dibucaine-hydrochloride in neutral and charged micellar solutions

Steady-state and time-resolved emission spectroscopic techniques have been employed to characterize the drug species of dibucaine and to identify its location in micellar Triton X-100 (neutral), hexadecyltrimethyl ammonium bromide (cationic) and lithium dodecyl sulfate (anionic) solutions at 77 K. Under physiological conditions, the dibucaine is shown to exist in the free base form (D) while solubilized in the hydrocarbon core of neutral micelles. In cationic micellar solution, dibucaine exists as the monocation species (DH+) where the anesthetic is solubilized in the extramicellar aqueous solution and D is solubilized in the hydrophobic region with close proximity to the micellar interface. In the anionic micelles, interfacial solubilization is most consistent with a site in which the tertiary amino group of the monocation dibucaine (DH+) is anchored at the micellar interface with its quinoline analog penetrating the hydrophobic region. The distinct properties observed for the drug species (i.e. D and DH+) and their solubilization sites in micelles are consistent with a balance between hydrophobic forces, surface polarity and the interfacial electrostatic potential present in the micellar solubilization sites. These observations could lend insight into the molecular basis of pharmacological action, in particular the mechanism of local anesthetic drug transport across membranes.