macrocycles

Macrocycles are cyclic chemical compounds in which the ring contains a relatively large number of atoms, typically 12 or more. They can be composed entirely of carbon or incorporate heteroatoms such as oxygen, nitrogen, or sulfur. Macrocycles arise in organic, inorganic, and organometallic chemistry and are distinguished from smaller rings by their size, conformational diversity, and potential to form defined cavities that bind guest molecules.

Many macrocycles exhibit preorganization: their ring structure positions donor atoms in a way that favors selective complexation of ions or small molecules. The balance between ring-closure enthalpy and the entropic cost of forming a large ring influences yield and conformations. Depending on their architecture, macrocycles range from relatively flexible to rigid, and their cavities can be tuned by substituents.

Well-known classes include crown ethers, cryptands, and related polyether macrocycles used to bind metal ions; cyclodextrins and calixarenes as supramolecular hosts; porphyrins and phthalocyanines as conjugated macrocycles with optical properties; cucurbiturils; cyclopeptides and other cyclic peptides. Macrolides are large lactone-containing antibiotics that feature macrocyclic rings.

Synthesis often relies on macrocyclization strategies, such as high-dilution cyclization, template assistance, or ring-closing metathesis. Design challenges include controlling ring size, avoiding oligomerization, and achieving the desired conformation. Advances in dynamic covalent chemistry and noncovalent templating have expanded accessible macrocycles.

Applications span metal ion binding and catalysis as macrocyclic ligands, drug delivery and solubilization using cyclodextrins, molecular recognition in sensors and separation technologies, and the development of functional materials in supramolecular chemistry.