Interaction of Chlorpromazine and Trifluoperazine with Anionic Sodium Dodecyl Sulfate (SDS) Micelles: Electronic Absorption and Fluorescence Studies

Abstract

The characteristics of binding of two phenothiazine antipsychothic drugs, chlorpromazine (CPZ) and trifluoperazine (TFP), to anionic sodium dodecyl sulfate (SDS) monomers and/or micelles were investigated using electronic absorption and fluorescence spectroscopies. Binding constants Kb and pKa values for the drugs in SDS micelles were estimated using the red shifts of the maximum absorption and changes in absorption upon alkalization or in the presence of surfactant. The pKa shift of CPZ due to its interaction with SDS micelles is about 0.7 unit to higher values, as compared to the reported value of pKa obtained in buffer around 9.3. For TFP the pKa shift is 0.4 unit to higher values compared to that in buffer, reported as 4.0. The electronic absorption spectroscopic data suggest a biphasic interaction as a function of detergent concentration which is quite dependent of the protonation states of the drugs. In the case of TFP a very strong binding takes place when the drug is fully protonated (pH 2.0) and a distinct binding takes place at stoichiometric (low) surfactant concentrations (interaction via surfactant monomers) and at higher concentrations (in the presence of micelles). Static fluorescence probe analysis using pyrene was used to study the nature of the phenothiazine–surfactant premicellar and self-aggregates. The I3/I1 and I475/I1 ratios associated to pyrene fluorescence vibronic bands and excimer intensities ratios, respectively, were monitored for several ratios [SDS]/[drug] and significant changes, dependent of the drug presence and its protonation state, have been observed revealing a hydrophobic microenvironment provided by TFP–SDS aggregates in comparison with CPZ both at pH 7.0 and 4.0. Static anisotropy was also used to monitor the changes of the self-aggregates and micellar packing in the presence of the phenothiazine drugs. In aqueous solutions the anisotropy of the fluorescent probe dipyridamole (DIP) is quite low, being around 0.005 at pH 7.0 and 0.025 at pH 4.0, and the addition of detergent leads to an increase in the values of anisotropy to 0.030 at pH 7.0 and 0.070 at pH 4.0. In the presence of the phenothiazine drugs, and in the premicellar detergent concentration range, the anisotropy of DIP increases to 0.134 and 0.111 (dependent on drug concentration) for CPZ and TFP, respectively, at pH 4.0. These results suggest that the presence of both phenotiazine drugs makes the premicellar aggregates more rigid by decreasing the probe mobility, and are consistent with a more polar localization of the CPZ in the micelles as compared with TFP. At pH 7.0 the anisotropy changes are smaller, suggesting a slight decrease in CMC induced by the phenothiazines.