Indrajit Ghosh

• Enzymes are unique in their ability to shift the pKa values of substrates by up to 5 units and thus catalyze acid–base reactions. Drawing inspiration from nature, chemists have long endeavored to design host molecules capable of modifying the protonation state of encapsulated guest molecules to catalyze their chemical reactions and thereby mimic biological effects in supramolecular assemblies. This doctoral thesis deals with the investigations of bio-mimetic supramolecular pKa shifts in different host–guest complexes, and the translation of this physicochemically interesting supramolecular phenomenon into practically relevant applications. The first part of this thesis demonstrates the successful employment of cucurbit[n]uril (a synthetic class of macrocycles) -induced pKa shifts to enhance the bioavailability (activity, solubility, ionization degree, and photostability) of drug molecules. Furthermore, a structure–activity relationship, which allows predictions of cucurbit[n]uril-induced absolute pKa shifts of encapsulated guest molecules, is discussed as well. The second part of this thesis describes a strategic supramolecular approach to modulate the excited state protonation-coupled electron transfer and photo-induced electron transfer properties of ditopic donor–acceptor type molecules. Such host-assisted modulation not only facilitates the electron transfer between two interacting redox partners of a guest molecule in a completely different solution condition, but also allows the development of fluorescence-based host–guest reporter pairs for the detection of optically-inactive, biologically important analytes via an indicator displacement approach. In the third part of the thesis, employment of size- and shape-selective molecular recognition in the design and development of heterocapsule-type ternary nanostructures is discussed. The obtained nanostructures show markedly different fluorescence and chiro-optical properties with respect to the guest molecules, and therefore, have enormous potential in modulating the circularly polarized luminescence properties of encapsulated guests. Finally, the effects of supramolecular host molecules on the photophysical properties of aggregation-prone fluorescent dyes and polymers are documented. Isolation, or rather separation, of the dye molecules from each other via a supramolecular approach, and the formation of mechanically interlocked rotaxane architectures immensely improved the photophysical properties of the investigated molecules.