Mechanically interlocked molecules (MIMs) such as rotaxanes and catenanes attract significant interest due to their unique structures and dynamic properties. Cyclodextrin-based rotaxanes (CD-rotaxanes) have emerged as promising supramolecular systems for biological and medicinal applications. Their host-guest interactions and mechanical bonds provide enhanced stability, stimuli-responsiveness, and tunable functionality. This review highlights their roles in targeted therapy, controlling drug release, theranostic agents, enzyme inhibitor, gene transport and bioimaging. Challenges and future perspectives in translating CD-rotaxanes to biomedical applications are discussed, emphasizing their potential as a next-generation therapeutic platform.

Inspired by interlocked oligonucleotides, peptides and knotted proteins, synthetic systems where a macrocycle cages a bioactive species that is “switched on” by breaking the mechanical bond have been reported. However, to date, each example uses a bespoke chemical design. Here we present a platform approach to mechanically caged structures wherein a single macrocycle precursor is diversified at a late stage to include a range of trigger units that control ring opening in response to enzymatic, chemical, or photochemical stimuli. We also demonstrate that our approach is applicable to other classes of macrocycles suitable for rotaxane and catenane formation.

We report a mild, metal-free synthesis of 2,5-disubstituted thiazoles from readily available N-substituted α-amino acids. The reaction proceeds via carboxylic acid activation with thionyl chloride, followed by intramolecular cyclization and in situ sulfoxide deoxygenation, affording the target thiazoles in excellent yields. This transition-metal-free, robust, and scalable protocol enables access to a broad range of 2,5-disubstituted thiazoles, bypassing the need for complex reagents and significantly simplifying their synthesis.