title: Charge- and pH-dependent binding sites for dibucaine in ionic micelles: a fluorescence study.
abstract: Binding of micromolar concentrations of the local anesthetic dibucaine to micelles of cationic, zwitterionic and anionic detergents was studied using the fluorescence emission of dibucaine. Difference in quantum yields for charged and neutral dibucaine allowed to obtain shifts of pKa values due to binding. Estimates for the electrostatic potential affecting the tertiary amine of dibucaine were obtained from the pKa shifts. Change of fluorescence emission upon binding allowed to obtain the binding constants of both charged and neutral dibucaine to the micelles. The binding constant for the neutral form is essentially independent of micelle charge and of specific differences in detergent structure. Consistency between the ratio of neutral to cationic dibucaine binding constants and the measured pKa shift was tested. For LPC micelles complete agreement was found. For CTAC, however, the ratio of binding constants does not explain the pKa shift. The discrepancy between the results is used to estimate the errors involved upon neglecting non-coulombic electrostatic interactions of drugs to charged membrane surfaces. Fluorescence quenching with sodium iodide and nitroxide stearic acid derivatives allowed a depth profiling of the drug in the micelles.
authors.affiliation: Instituto de Física e Química de São Carlos, Universidade de São Paulo, Brazil.
authors.forename: S R
authors.initials: SR
authors.lastname: Louro
authors.forename: O R
authors.initials: OR
authors.lastname: Nascimento
authors.forename: M
authors.initials: M
authors.lastname: Tabak
mesh_terms: D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D001665:Binding Sites; D002021:Buffers; D000077286:Cetrimonium; D002593:Cetrimonium Compounds; D003902:Detergents; D003992:Dibucaine / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008244:Lysophosphatidylcholines; D008823:Micelles; D013050:Spectrometry, Fluorescence; D013499:Surface Properties
chemical_list: D002021:Buffers; D002593:Cetrimonium Compounds; D003902:Detergents; D008244:Lysophosphatidylcholines; D008823:Micelles; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D003992:Dibucaine; D000077286:Cetrimonium