Design and synthesis of cyclodextrin-based materials as multi-purpose supramolecular platforms

Cyclodextrins (CDs) are hydrophilic, biocompatible macrocycles composed of α-D-glucopyranose units joined together by α(1-4) linkages. Thanks to the presence of many different hydroxyl (-OH) groups on their outer surface, CDs present high solubility in water. However, the space confined inside their cavity is endowed with a hydrophobic character enabling supramolecular, non-covalent interactions with a variety of organic substrates. The most popular CDs consist of 6, 7 or 8 glucose units (α-, β- and γCD, respectively) possessing different ring size. This feature, combined with the possibility to regioselectively modify one or more -OHs, strongly enhances their capability to form specific host:guest complexes with organic targets enabling the use of CDs in different fields of application, from pharmaceutical to environmental and catalysis. Digging at the edge between organic and supramolecular chemistry, the design and synthesis of mono-, poly- and fully substituted CDs bearing selected functional groups were performed to enhance their binding properties towards selected molecules. Regio-selective modification could be achieved exploiting the different reactivity of the -OH groups in positions 2, 3 and/or 6 of the glucose units. Cationic1 and anionic2 CDs were synthesized in order to combat antimicrobial resistance mechanisms upon stabilization of negatively charged drugs and chelation of metal cations, respectively. Moreover, the preparation of CD-polymers crosslinked with epichlorohydrin was performed in order to co-encapsulate simultaneously more than one therapeutic agent.3 Moreover, these polymers could be used as inert support for the photocatalytic conversion of aromatic substrates into their corresponding endoperoxides and the resulting supramolecular entities were tested as oxygen-releasing agents. The release of trapped molecular oxygen upon thermolysis could be exploited for targeting and relieving hypoxia in malignant diseases.4