A macrocycle is, as defined by IUPAC, "a cyclic macromolecule or a macromolecular cyclic portion of a molecule. The International Union of Pure and Applied Chemistry ( IUPAC) (aɪjuːpæk or ay-yoo-pec) is an international Non-governmental organization "^[1] In the chemical literature, organic chemists may consider any molecule containing a ring of more than nine, or any arbitrarily large number of atoms (3 of them "donor atom") to be macrocyclic.

Macrocycle Effect

Crystal structure of a Zn(II) ion coordinated to cyclen and ethanol reported in Inorg. Cyclen or 14710-tetraazacyclododecane is a Macrocycle and the Aza analogue of the Crown ether 12-crown-4. Chem. , 1997, 4579-4584.

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). Chelation is the binding or complexation of a bi- or multidentate Ligand. In Chemistry, a ligand is either an Atom, Ion, or Molecule (see also Functional group) that bonds to a central metal generally In Chemistry, a ligand is either an Atom, Ion, or Molecule (see also Functional group) that bonds to a central metal generally 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. In Thermodynamics (a branch of Physics) entropy, symbolized by S, is a measure of the unavailability of a system ’s Energy Binding energy is the Mechanical energy required to disassemble a whole into separate parts 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). Cryptands are a family of synthetic bi- and polycyclic multidentate Ligands for a variety of cations

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. Intramolecular in Chemistry describes a process or characteristic limited within the structure of a single Molecule; a property or phenomenon limited to the extent Because the formation of macrocycles uses the same chemistry that polymerization does, steps need to be taken to prevent polymerization from occurring. In Polymer chemistry, polymerization is a process of reacting Monomer Molecules together in a Chemical reaction to form three-dimensional networks 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. In Chemistry, the term transition metal (sometimes also called a transition element) has two possible meanings It commonly refers to any element in ” 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. Chelation therapy is the administration of chelating agents to remove Heavy metals from the body EDTA is a widely used abbreviation for the Chemical compound ethylenediaminetetraacetic acid (and many other names see table

• 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. A molecular switch is a Molecule that can be reversibly shifted between two or more stable states Nanotechnology, sometimes shortened to nanotech, refers to a field of Applied science whose theme is the control of matter on an Atomic and Molecular Peptides (from the Greek πεπτίδια, "small digestibles" are short Polymers formed from the linking in a defined order of α- Amino In Pharmacology, a small molecule is a small Organic compound that is biologically active ( Biomolecule) but is not a Polymer. An Organic Light Emitting Diode ( OLED) also Light Emitting Polymer ( LEP) and Organic Electro Luminescence ( OEL) is any 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. A phthalocyanine is a macrocyclic compound having an alternating nitrogen atom-carbon atom ring structure. A porphyrin is a heterocyclic Macrocycle derived from four Pyrroline subunits interconnected via their α carbon atoms via Methine bridges (=CH- 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. A heme ( American English) or haem ( British English) is a Prosthetic group that consists of an Iron atom contained in the center of Hemoglobin ( also spelled haemoglobin and abbreviated Hb or Hgb) is the Iron -containing Oxygen -transport Metalloprotein Blood is a specialized Bodily fluid that delivers necessary substances to the body's cells ��such as nutrients and oxygen—and transports Waste products A porphyrin is a heterocyclic Macrocycle derived from four Pyrroline subunits interconnected via their α carbon atoms via Methine bridges (=CH-
• Chlorophyll, the green photosynthetic pigment found in plants contains a chlorin ring. Chlorophyll is a green Pigment found in most Plants Algae and Cyanobacteria. A photosynthetic pigment ( accessory pigment; chloroplast pigment; antenna pigment) is a Pigment that is present in Chloroplasts or Plants are living Organisms belonging to the kingdom Plantae. In Organic chemistry, a chlorin is a large Heterocyclic Aromatic ring consisting at the core of three Pyrroles and one Pyrroline
• Vitamin B12, contains a corrin ring. A corrin is a Macrocycle related to the Porphyrin ring in Hemoglobin, consisting of 4 Pyrrole subunits joined on opposite sides by a C-CH3

Related Molecular Categories

• Ligand: an atom, ion or functional group that is bonded to one or more central atoms or ions. In Chemistry, a ligand is either an Atom, Ion, or Molecule (see also Functional group) that bonds to a central metal generally
• Chelate: a multidentate ligand, containing more than one donor atom. Chelation is the binding or complexation of a bi- or multidentate Ligand.
• Cryptand: a macrocycle with multiple loops (e. Cryptands are a family of synthetic bi- and polycyclic multidentate Ligands for a variety of cations g. bicyclic).
• Rotaxane: macrocycle(s) stuck on a stick, generally freely rotating. A rotaxane is a mechanically-interlocked molecular architecture consisting of a "dumbbell shaped molecule" which is threaded through a " Macrocycle
• Catenane: interlocked molecular rings (like a chain). A catenane is a mechanically-interlocked molecular architecture consisting of two or more interlocked Macrocycles The interlocked rings cannot be separated
• Molecular knot: a molecule in the shape of a knot such as a trefoil knot. In Chemistry, a molecular knot (knotane is a mechanically-interlocked molecular architecture that is analogous to a macroscopic Knot. In Knot theory, the trefoil knot is the simplest nontrivial knot.

References

1. ^  International Union of Pure and Applied Chemistry. The International Union of Pure and Applied Chemistry ( IUPAC) (aɪjuːpæk or ay-yoo-pec) is an international Non-governmental organization "macrocycle". Compendium of Chemical Terminology Internet edition. Compendium of Chemical Terminology (ISBN 0-86542-684-8 is a book published by IUPAC containing internationally accepted definitions for terms in Chemistry.
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.

Further reading

• Chambron, J-C. ; Dietrich-Buchecker, C. ; Hemmert, C. ; Khemiss, A-K. ; Mitchell, D. ; Sauvage, J-P. ; Weiss, J. (1990). "Interlacing molecular threads on transition metals". Pure Appl. Chem. 62 (6): 1027-34. Pure and Applied Chemistry (abb Pure Appl Chem) is the official journal for the International Union of Pure and Applied Chemistry.