Mechanosynthesis of β-Cyclodextrin Polymers Based on Natural Deep Eutectic Solvents

Beta-cyclodextrin (βCD)-based polymers are a class of materials that have been found in the last decade in many different applications in various fields such as pharma, food, and environment. Unfortunately, most syntheses of βCD-based polymers require the use of organic solvents or toxic reactants which may affect potential environmental or biomedical applications. Research is now moving toward more sustainable approaches and new and greener syntheses: in this context, we report here a new, eco-friendly, and efficient synthesis of βCD polymers based on the combination of mechanochemistry and natural deep eutectic solvents (NaDESs). NaDESs represent a green replacement for oil-based solvents but suffer from the intrinsic criticalities in their use and production, mainly related to the technical difficulties of mixing solid reactants to make a high viscosity liquid. Moreover, the reported syntheses of βCD polymers are driven under vacuum, and this is a major limitation in a possible scale-up of the reaction. The new synthesis of water-soluble βCD-based polymers here reported exploits choline chloride/citric acid NaDESs and is conducted using different mechanochemical approaches. Mechanochemistry involves the application of mechanical forces to drive and control chemical reactions by transferring energy to chemical bonds. Mechanosynthesis is meant to be "solvent-free,"but actually in some cases, the reaction can occur in the presence of solvent or, as in this case, with liquid reagents, acting as solvents. The use of mechanochemistry permitted us to overcome the limitations of a traditional NaDES reaction, mainly related to the high viscosity of the NaDES and to the necessity to work under vacuum. We first demonstrated the possibility to easily obtain a choline chloride/citric acid NaDES using two different apparatuses, a ball mill and a twin-screw extruder, and then the possibility to use the same instruments for the synthesis of a soluble polymer. Eventually, the soluble polymers from mechanochemical syntheses were thermally treated to obtain a cross-linked insoluble structure. The soluble and insoluble polymers were characterized with different techniques and compared, demonstrating substantial differences regarding the diverse mechanochemical approaches.