Macrocycles are often described as molecules and ions containing a ring of twelve or more atoms. Classical examples include the
crown ethers,
calixarenes,
porphyrins, and
cyclodextrins. 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 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
crown ethers 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.
:
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. Ma ...
s, e.g.
clarithromycin. Many metallocofactors are bound to macrocyclic ligands, which include
porphyrins,
corrins, and
chlorins. 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 transition of a reactant from one phase into another phase where reaction occurs. Phase-transfer catalysis is a special form of heterogeneous catalysis. Ionic r ...
properties.
Macrocycles are often bioactive and could be useful for drug delivery.
Subdivisions
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Cryptand
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Rotaxane
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Catenane
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Molecular knot
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Effective molarity
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Macrocyclic stereocontrol
See also
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Macrocyclic ligand
References
Further reading
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*{{Cite journal, last=Iyoda, first=Masahiko, last2=Yamakawa, first2=Jun, last3=Rahman, first3=M. Jalilur, date=2011-11-04, title=Conjugated Macrocycles: Concepts and Applications, journal=Angewandte Chemie International Edition, language=en, volume=50, issue=45, pages=10522–10553, doi=10.1002/anie.201006198, pmid=21960431, issn=1521-3773