Supramolecular cucurbituril complexes for applications in bio-relevant contexts

Resum

In the last decade, macrocyclic hosts have been used as an exciting new tool in functional supramolecular chemistry applications ranging from sensing, via drug delivery to catalysis and materials chemistry. This doctoral thesis describes the development of new supramolecular systems based on cucurbiturils for biologically related applications. Adequate water solubility, low toxicity, and capacity to form strong host-guest complexes, establish cucurbituril chemistry as a powerful tool to investigate and possibly modulate biological systems and functions. Likewise, their ability to tune photophysical and chemical properties of encapsulated guests were exploited by the use of UV/vis, mass spectrometry, liquid chromatography, NMR, and fluorescence-based techniques. Moreover, taking advantage of molecular biology procedures the effects of cucurbiturils on enzymatic activity were investigated. In this work, for the first time a proof-of-principle for the photo-triggered delivery of a drug by disassembly of its host-guest complex with CB7, taking advantage of a pH jump, is described. Additionally, an anchor approach was developed, which enabled the improvement of the hydrolytic stability of spiropyrans in aqueous solution without compromising their switching performance. Furthermore, it is described for the first time that CB6 and CB7 can influence directly enzymatic activity of endonucleases, which can be reversibly controlled by the use of strong competitors for the macrocyclic host cavity. This consolidates the possibility of supramolecular control of biocatalytic processes. Finally, the chemically and photonically driven operation of a supramolecular keypad lock device with a ternary anthracene-guest/CB8 host complex is described. The reversible and robust photoinduced cycloaddition reaction in the cavity of the host is remarkable. In general terms, this work broadens further the use of cucurbituril macrocyclic hosts in the context of functional chemistry and biological applications.