Macrocycle

A macrocycle is, as defined by IUPAC, "a cyclic macromolecule or a macromolecular cyclic portion of a molecule."^[1] In the chemical literature, organic chemists may consider any molecule containing a ring of seven, fifteen, or any arbitrarily large number of atoms to be macrocyclic.

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Macrocycle Effect

  Coordination chemists study macrocycle with three or more potential donor atoms in rings of greater than nine atoms as these compounds often have strong and specific binding with metals.^[2] This property of coordinating macrocyclic molecules is the macrocycle effect. It is in essence a specific case of the chelation effect: complexes of bidentate and polydentate ligands are more stable than those with unidentate ligands of similar strength (or similar donor atoms). A macrocycle has donor atoms arranged in more fixed positions and thus there is less of an entropic effect in the binding energy of macrocycles than monodentate or bidentate ligands with an equal number of donor atoms. Thus the macrocycle effect states that complexes of macrocyclic ligands are more stable than those with linear polydentate ligands of similar strength (or similar donor atoms). The same can be said for multicyclic macrocycles, or cryptates, being stronger complexing agents (a cryptate effect).

Synthesis

Macrocycles are generally synthesized from smaller, usually linear, molecules. To create a ring, either an intermolecular reaction, where two or more molecules come together in a reaction to form a ring, or an intramolecular reaction, where one molecule reacts with itself to form a ring, must occur. Because the formation of macrocycles uses the same chemistry that polymerization does, steps need to be taken to prevent polymerization from occurring. Traditionally, this involved high dilution chemistry where large amounts of solvent and low concentrations were used to prevent molecules from reacting with other molecules. Also, the reagents frequently needed to be added slowly. At low concentration, the molecule is more likely to react with itself than with another molecule. This is generally inefficient, using large quantities of solvents and giving low yields.

To achieve high yields of macrocycles at high concentrations, a way to orient the reactive sites such that they readily undergo cyclization was needed. Transition metals, with their ability to gather & dispose of ligands in a given predictable geometry, can induce a “template effect.” By binding to the linear molecule, to influence its geometry, a metal "template" can accelerate either the intramolecular or the intermolecular reaction. Thus the judicious choice of a metal ion and the relative locations of donor atoms would allow a metal to control the cyclization process.

The template effect can be divided into two slightly more specific effects: The kinetic template effect describes the directive influence of the metal ion controls the steric course of a sequence of stepwise reactions. In cases where the thermodynamic template effect operates, the metal ion perturbs an existing equilibrium in an organic system and the required product is produced often in high yield as a metal complex. In most cases, the kinetic template effect is operative, however an assignment cannot be made in all cases. ^[3]

Applications

• Removal of heavy metals from aqueous solution for water purification.

  • Chelation therapy whereby the use of chelating agents such as EDTA to remove heavy metals from the body.

• Molecular switches and linear motors for constructing artificial nanoscale machinery (rotaxanes)
• Chemical Sensors
• Mimicry of cellular receptors
• Molecular recognition

  • Recognition of peptides^[4]
  • Small molecules

• Organic light-emitting diodes (OLEDs)

Historical Uses

Macrocycles have been in use for several decades as synthetic dyes. Phthalocyanine is a porphyrin analogue, which is arguably the most useful, in uses as dyes and pigments since their discovery in 1928, due to their dark blue colour. There are however many other uses for them. Their name comes from their synthetic precursor, phthalodinitrile.^[5]

Biological Macrocycles

• Heme, the active site in the hemoglobin (the protein in blood that transports oxygen) is a porphyrin containing iron.
• Chlorophyll, the green photosynthetic pigment found in plants contains a chlorin ring.
• Vitamin B12, contains a corrin ring.

Related Molecular Categories

• Ligand: an atom, ion or functional group that is bonded to one or more central atoms or ions.
• Chelate: a multidentate ligand, containing more than one donor atom.
• Cryptand: a macrocycle with multiple loops (e.g. bicyclic).
• Rotaxane: macrocycle(s) stuck on a stick, generally freely rotating.
• Catenane: interlocked molecular rings (like a chain).
• Molecular knot: a molecule in the shape of a knot such as a trefoil knot.

References

1. ^  IUPAC Compendium of Chemical Terminology 2nd Edition (1997)
2. ^  Milgrom, L.R (1997). The Colours of Life: An Introduction to the Chemistry of Porphyrins and Related Compounds. New York: Oxford University Press. ISBN 0-19-855380-3.  (hardbound) ISBN 0-19-855962-3 (pbk.)
3. ^  Melson, G.A., Ed. (1979). Coordination Chemistry of Macrocyclic Compounds. New York: Plenum Press. ISBN 0-306-40140-1. 
4. ^  Jung, J.E.; Seung, S.Y., Bulletin of the Korean Chemical Society 2002, 23(10) 1483-1486.