Dottorato in SCIENZE CHIMICHE

Titolo della tesi: A study of association in mixtures of amphiphilic molecules and polymers

This thesis incorporates the investigation of aqueous solutions of oppositely charged amphiphile systems. The interactions between a positively charged polymer and negatively charged steroidal surfactants is studied to better understand the interactions between dietary fibers and bile salts. The interactions between a negatively charged polymer and a positively charged drug molecule is studied to gain valuable information on the drug molecule’s self-association behavior in the presence of an anionic species. Through these studies, it is shown how the combination of hydrophobic and electrostatic interactions lead to unique self-association behavior and structure formation. In the first part of the thesis, the interactions between cationic hydroxyethyl cellulose (catHEC) and sodium deoxycholate (NaDC) or sodium cholate (NaC) were investigated to gain insight into the interactions between dietary fibers and bile salts. Dietary fibers are known to reduce the level of blood cholesterol through their interactions with bile salts in the gastrointestinal tract. Through turbidity measurements, catHEC was revealed to have strong interactions with NaDC, with macroscopic phase separation occurring under certain conditions. In contrast, the interactions with NaC were much weaker. At a catHEC concentration of 2 wt%, incipient phase separation was approached at concentrations of NaC and NaDC of 32.5 mM and 19.3 mM, respectively. The rheological results showed strong interactions and a prominent viscosification effect for the catHEC/NaDC system, but only moderate interactions for the catHEC/NaC system. Both cryo-TEM and SAXS results displayed fundamental structural differences between the two systems, which may explain the stronger interactions in the presence of NaDC. The surmise was that the extended structures formed in the presence of NaDC could easily form connections and entanglements in the network. In the second part of the thesis, the interactions between the positively charged fluorescent drug, doxorubicin (DX), and the negatively charged polyelectrolyte, polystyrene sulfonate (PSS), was studied. This study was to investigate the effect complexation with a polyanion has on DX’s self-association. DX is known to self-associate into non-fluorescent antiparallel dimers upon increasing concentration and/or ionic strength. The complexation of DX with PSS was monitored by fluorescence. The fluorescence emission of DX was found to decrease in the presence of PSS, being almost quenched when the ratio (R) of PSS monomers-to-DX molecules was larger than 10. Increasing the R value above 30 resulted in a progressive recovery of fluorescence. The circular dichroism of PSS-DX complexes showed inverted characteristic bands of DX dimers, which suggested the presence of parallel dimers at a concentration of DX below dimerization in water. Molecular dynamics studies showed the preferential orientation of DX into parallel dimers when interacting with PSS, and furthermore, they showed that DX molecules could interact with a binding pocket of PSS monomers instead of just one single monomer. Increasing the ionic strength resulted in a recovery of fluorescence without an apparent release of DX from the PSS-DX complex as shown by DOSY NMR. Finally, it could be concluded that PSS acts as a template for concentrating DX, triggering the formation of parallel DX dimers due to their charged groups facing the negatively charged PSS monomers.