Interaction of chlorpromazine and trifluoperazine with anionic sodium dodecyl sulfate (SDS) micelles: Electronic absorption and fluorescence studies

The characteristics of binding of two phenothiazine antipsychothic drugs, c hlorpromazine (CPZ) and trifluoperazine (TFP), to anionic sodium dodecyl su lfate (SDS) monomers and/or micelles were investigated using electronic abs orption and fluorescence spectroscopies. Binding constants K-b and pK(a) va lues for the drugs in SDS micelles were estimated using the red shifts of t he maximum absorption and changes in absorption upon alkalization or in the presence of surfactant. The pK(a) shift of CPZ due to its interaction with SDS micelles is about 0.7 unit to higher values, as compared to the report ed value of pK(a) obtained in buffer around 9.3. For TFP the pK(a) 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 prot onation 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 ta kes place at stoichiometric (low) surfactant concentrations (interaction vi a surfactant monomers) and at higher concentrations tin the presence of mic elles). Static fluorescence probe analysis using pyrene was used to study t he nature of the phenothiazine-surfactant premicellar and self-aggregates. The I-3/I-1 and I-475/I-1 ratios associated to pyrene fluorescence vibronic bands and excimer intensities ratios, respectively, were monitored for sev eral ratios [SDS]/[drug] and significant changes, dependent of the drug pre sence and its protonation state, have been observed revealing a hydrophobic microenvironment provided by TFP-SDS aggregates in comparison with CPZ bot h 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 phenoth iazine 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 conce ntration) for CPZ and TFP, respectively, at pH 4.0. These results suggest t hat the presence of both phenotiazine drugs makes the premicellar aggregate s more rigid by decreasing the probe mobility, and are consistent with a mo re polar localization of the CPZ in the micelles as compared with TFP. At p H 7.0 the anisotropy changes are smaller, suggesting a slight decrease in C MC induced by the phenothiazines. (C) 2000 Academic Press.