pH-Responsive Cyclodextrin-Surfactant Inclusion Complexes: Thermodynamics and Structural Aspects

This thesis presents the investigation of the multilevel assembly of the alkyl oligoethylenoxide carboxylic acids and cyclodextrins. The aim of the work is to combine the short-range host-guest and long-range electrostatic interactions to form highly-ordered supramolecular complexes. The interactions between the components affect their individual response and their properties; therefore, the knowledge of the nature and the influence of their chemical structure is essential to understand the system’s behaviour. Polyoxyethylene alkyl carboxylic acids are an attractive class of surfactants to integrate both inclusion complexes and polyelectrolyte systems due to their pH and thermoresponsiveness. The complementary combination approach of thermodynamic and structural investigations allowed probing the formation and responsiveness of the complexes. First, the inclusion complexes systems were studied by densitometry and isothermal titration calorimetry and a comprehensive structural investigation was conducted by small-angle neutron scattering, differential scanning calorimetry and microscopy. The spontaneous formation of the host-guest complexes at different pH was evidenced, and their assembly as building blocks of large supramolecular aggregates with rich structural behaviour was verified. Different aspects of these systems were studied, and it was possible to tune the structures by exploring the components’ concentration, cyclodextrin-to-surfactant ratio, and the pH response of the surfactants. The charge density plays an important role in directing the assembly into highlyordered cylindrical structures without drastically changing the thermodynamics of the inclusion complex formation. In addition, the analysis allowed to unveil the effect of the temperature, the chemical structure of the surfactants and the cyclodextrin on the morphology of the aggregates. Finally, the co-assembly between inclusion complexes and chitosan exploring the long-range electrostatic interactions was assessed in different aspects with a main focus on their structures and directing their assembly by controlling the pH and concentration of the systems. This thesis delivers a thermodynamic and structural complementary approach that allows designing supramolecular aggregates of the desired properties with potential applications in a variety of formulations. It also highlights the importance of evaluating the impact of the tuning parameters in the hierarchical assembly process from the short to the long-range interactions envisioning their systematic application.