Synthesis, characterization and interaction with ionic micelles of tetraacetylated dipyridamole

Abstract

Tetraacetylated dipyridamole (Ac-DIP) was synthesized by reaction of dipyridamole (DIP) with acetic anhydride in a quantitative yield. Infrared and NMR spectra showed that the acetylation was complete, yielding the expected new bands and the disappearance of hydroxyl bands in the IR and NMR spectra. Tetraacetylated DIP was analyzed by electronic absorption and fluorescence emission in different solvents. The solubility of Ac-DIP in water is considerably lower than that of DIP, and both the absorption and emission are shifted to the blue denoting a less efficient relaxation to the solvent. Extinction coefficients and quantum yields in ethanol, chloroform and dimethyl sulfoxide are very similar for Ac-DIP and DIP. 1H and 13C NMR spectra were obtained in deuterated chloroform and dimethyl sulfoxide and a complete assignment of peaks was obtained. In order to obtain more insight into the properties of Ac-DIP, the interaction of DIP and Ac-DIP with cationic cetyltrimethylammonium chloride (CTAC) and anionic sodium dodecyl sulfate (SDS) micelles was studied. In the presence of micelles the p K a of DIP changes considerably from its value in water: from 5.8 to 4.3 in CTAC and to 7.3 in SDS indicating a considerable interaction with micelles. The p K a of Ac-DIP in SDS is 5.8. For both compounds the interaction with micelles is predominantly hydrophobic in nature but for Ac-DIP it is less sensitive to the charge on the micelle and the degree of ionization of the drug. All the results suggest that Ac-DIP is significantly more hydrophobic than DIP, being probably quite efficient in the interaction with membrane systems. This could be quite relevant for its effect at the cellular level.