Design and synthesis of functional molecular systems CDK PROTACs and quinone rotaxane-based electron shuttles

This thesis explores the design and synthesis of functional molecular systems in two distinct areas: targeted protein degradation and mechanically interlocked redox-active molecules. The first part focuses on medicinal chemistry and the development of cyclin-dependent kinase (CDK) PROTACs. Building on modular synthetic strategies, including multicomponent reaction chemistry, a series of cereblon-recruiting degraders based on an abemaciclib-derived CDK ligand was prepared and evaluated. Selected compounds showed activity consistent with degradation of CDK4, CDK6 and CDK9, while alternative E3-ligase recruitment strategies were also investigated.
The second part examines quinone-containing rotaxanes as structurally defined platforms for redox control and, ultimately, molecular electron-shuttling systems. Synthetic routes were developed to access covalent quinone [2]rotaxanes and complementary supramolecular redox-active rotaxane modules. Particular attention was paid to how mechanical interlocking and the local chemical environment influence quinone reduction. Electrochemical studies showed that positioning carboxylic acid groups close to the quinone units through mechanical preorganization can substantially modify their reduction behaviour, consistent with proton-assisted or proton-coupled processes, whereas related amide-containing systems show much smaller effects.
Together, these studies illustrate how molecular function can be programmed through modular synthesis, spatial organization and controlled proximity, from induced protein degradation to mechanically regulated redox chemistry.