Macrocycles are often described as molecules and ions containing a ring of twelve or more atoms. Classical examples include the

crown ether In organic chemistry, crown ethers are cyclic chemical compounds that consist of a ring containing several ether groups (). The most common crown ethers are cyclic oligomers of ethylene oxide, the repeating unit being ethyleneoxy, i.e., . I ...

calixarene A calixarene is a macrocycle or cyclic oligomer based on a methylene-linked phenols. With hydrophobic cavities that can hold smaller molecules or ions, calixarenes belong to the class of cavitands known in host–guest chemistry. Nomenclature C ...

porphyrin Porphyrins ( ) are a group of heterocyclic macrocycle organic compounds, composed of four modified pyrrole subunits interconnected at their α carbon atoms via methine bridges (=CH−). The parent of porphyrin is porphine, a rare chemical ...

s, and

cyclodextrin Cyclodextrins are a family of cyclic oligosaccharides, consisting of a macrocyclic ring of glucose subunits joined by α-1,4 glycosidic bonds. Cyclodextrins are produced from starch by enzymatic conversion. They are used in food, pharmaceutica ...

s. Macrocycles describe a large, mature area of chemistry.

Synthesis

The formation of macrocycles by ring-closure is called macrocylization. Pioneering work was reported for studies on

terpenoid The terpenoids, also known as isoprenoids, are a class of naturally occurring organic chemicals derived from the 5-carbon compound isoprene and its derivatives called terpenes, diterpenes, etc. While sometimes used interchangeably with "terpenes ...

macrocycles. The central challenge to macrocyclization is that ring-closing reactions do not favor the formation of large rings. Instead, small rings or polymers tend to form. This kinetic problem can be addressed by using high-dilution reactions, whereby intramolecular processes are favored relative to polymerizations. Some macrocyclizations are favored using template reactions. Templates are ions, molecules, surfaces etc. that bind and pre-organize compounds, guiding them toward formation of a particular ring size. The

s are often generated in the presence of an alkali metal cation, which organizes the condensing components by complexation. An illustrative macrocyclization is the synthesis of (−)-

muscone Muscone is an organic compound that is the primary contributor to the odor of musk. The chemical structure of muscone was first elucidated by Leopold Ružička. It consists of a 15-membered ring ketone with one methyl substituent in the 3-positi ...

from (+)-

citronellal Citronellal or rhodinal ( C10 H18 O) is a mono terpenoid aldehyde, the main component in the mixture of terpenoid chemical compounds that give citronella oil its distinctive lemon scent. Citronellal is a main isolate in distilled oils from the ...

. The 15-membered ring is generated by ring-closing metathesis. : Uroporphyrinogen III skeletal

Occurrence and applications

One important application are the many macrocyclic antibiotics, the

macrolide The Macrolides are a class of natural products that consist of a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered. M ...

s, e.g.

clarithromycin Clarithromycin, sold under the brand name Biaxin among others, is an antibiotic used to treat various bacterial infections. This includes strep throat, pneumonia, skin infections, '' H. pylori'' infection, and Lyme disease, among others. Clar ...

. Many metallocofactors are bound to macrocyclic ligands, which include

corrin Corrin is a heterocyclic compound. It is the parent macrocycle related to the substituted derivative that is found in vitamin B12. Its name reflects that it is the "core" of vitamin B12 ( cobalamins).Nelson, D. L.; Cox, M. M. "Lehninger, Princ ...

s, and

chlorin In organic chemistry, chlorins are tetrapyrrole pigments that are partially hydrogenated porphyrins. The parent chlorin is an unstable compound which undergoes air oxidation to porphine. The name chlorin derives from chlorophyll. Chlorophylls ...

s. These rings arise from multistep biosynthetic processes that also feature macrocycles. Macrocycles often bind ions and facilitate

ion transport In biology, a transporter is a transmembrane protein that moves ions (or other small molecules) across a biological membrane to accomplish many different biological functions including, cellular communication, maintaining homeostasis, energy produc ...

across hydrophobic membranes and solvents. The macrocycle envelops the ion with a hydrophobic sheath, which facilitates

phase transfer In chemistry, a phase-transfer catalyst or PTC is a catalyst that facilitates the Phase transition, transition of a reactant from one phase (matter), phase into another phase where reaction occurs. Phase-transfer catalysis is a special form of het ...

properties. Macrocycles are often bioactive and could be useful for drug delivery.

Subdivisions

* Cryptand *

Rotaxane In chemistry, a rotaxane () is a mechanically interlocked molecular architecture consisting of a dumbbell-shaped molecule which is threaded through a macrocycle (see graphical representation). The two components of a rotaxane are kinetically ...

Catenane In macromolecular chemistry, a catenane () is a mechanically interlocked molecular architecture consisting of two or more interlocked macrocycles, i.e. a molecule containing two or more intertwined rings. The interlocked rings cannot be se ...

Molecular knot In chemistry, a molecular knot is a mechanically interlocked molecular architecture that is analogous to a macroscopic knot. Naturally-forming molecular knots are found in organic molecules like DNA, RNA, and proteins. It is not certain that nat ...

Effective molarity In chemistry, the effective molarity (denoted ''EM'') is defined as the ratio between the first-order rate constant of an intramolecular reaction and the second-order rate constant of the corresponding intermolecular reaction (''Kinetic Effective M ...

Macrocyclic stereocontrol Macrocyclic stereocontrol refers to the directed outcome of a given intermolecular or intramolecular chemical reaction, generally an organic reaction, that is governed by the conformational or geometrical preference of a carbocyclic or heterocyc ...

Synthesis

Occurrence and applications

Subdivisions

See also

References

Further reading