porphyrin

[pawr-fuh-rin]

Any of a class of biologically important heterocyclic compounds of a characteristic chemical structure that includes four pyrrole groups (five-membered organic rings each containing a nitrogen atom) linked by additional carbon atoms to form a large flat ring. As biological pigments, they and closely related molecules are responsible for many of the vivid colours in living organisms, where they often occur combined with metal ions and various substituents as coordination complexes (see compound). These include the magnesium-containing chlorophylls and the iron-containing heme group, a constituent (along with protein) of, e.g., hemoglobin, the cytochromes, and the enzyme catalase. In medicine, porphyrins are used in conjunction with light, often a laser beam, to induce reactions in the body against cancer and other diseases.

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Encyclopedia Britannica, 2008. Encyclopedia Britannica Online.

Porphyrin

A porphyrin is a heterocyclic macrocycle derived from four pyrroline subunits interconnected via their α carbon atoms via methine bridges (=CH-). Porphyrins are aromatic and they obey Hückel's rule for aromaticity in that they possess 4n+2 pi electrons which are delocalized over the macrocycle. The macrocycle, therefore, is a highly-conjugated system, and, as a consequence, is deeply coloured - the name porphyrin comes from a Greek word for purple. The macrocycle has 22 pi electrons. The parent porphyrin is porphine, and substituted porphines are called porphyrins. Many porphyrins occur in nature, such as in green leaves and red blood cells, and in bio-inspired synthetic catalysts and devices.

Complexes of porphyrins and related molecules

Porphyrins bind metals to form complexes. The metal ion, usually with a charge of 2+ or 3+, is in the central N₄ cavity formed by the loss of two protons. Most metals can be inserted. A schematic equation for these syntheses is shown:

H₂porphyrin + [ML_n]²⁺ → M(porphyrinate)L_n-4 + 4 L + 2 H⁺

A porphyrin in which no metal is inserted in its cavity is sometimes called a free base. Some iron-containing porphyrins are called hemes; and heme-containing proteins, or hemoproteins, are found extensively in nature. Hemoglobin and myoglobin are two O₂-binding proteins that contain iron porphyrins.

Related to porphyrins are several other heterocycles, including corrins, chlorins, bacteriochlorophylls, and corphins. Chlorins (2,3-dihydroporphyrin) are more reduced, that contain more hydrogen, than porphyrins, featuring a pyrroline subunit. This structure occurs in chlorophyll. Replacement of two of the four pyrrolic subunits with pyrrolinic subunits results in either a bacteriochlorin (as found in some photosynthetic bacteria) or an isobacteriochlorin, depending on the relative positions of the reduced rings. Some porphyrin derivatives follow Hückel's rule, but most do not.

Laboratory synthesis

One of the more common syntheses for porphyrins is based on work by Paul Rothemund. His techniques underpin more modern syntheses such as those described by Alder and Longo. The synthesis of simple porphyrins such as meso-tetraphenylporphyrin is also commonly done in university teaching labs.

In this method, porphyrins are assembled from pyrrole and substituted aldehydes. Acidic conditions are essential; formic acid, acetic acid, and propionic acid are typical reaction solvents, or p-toluenesulfonic acid can be used with a non-acidic solvent. Lewis acids such as boron trifluoride etherate and ytterbium triflate have also been known to catalyse porphyrin formation. A large amount of side-product is formed and is removed, usually by chromatography.

Biosynthesis

The "committed step" for porphyrin biosynthesis is the formation of D-aminolevulinic acid (dALA) by the reaction of the amino acid glycine and succinyl-CoA, from the citric acid cycle. Two molecules of dALA combine to give porphobilinogen (PBG), which contains a pyrrole ring. Four PBGs are then combined through deamination into hydroxymethyl bilane (HMB), which is hydrolysed to form the circular tetrapyrrole uroporphyrinogen III. This molecule undergoes a number of further modifications. Intermediates are used in different species to form particular substances, but, in humans, the main end-product protoporphyrin IX is combined with iron to form heme. Bile pigments are the breakdown products of heme.

The following scheme summarizes the biosynthesis of porphyrins, with references by EC number and the OMIM database. The porphyria associated with the deficiency of each enzyme is also shown:

Enzyme	substrate	Product	Chromosome	EC	OMIM	porphyria
ALA synthase	Glycine, succinyl CoA	D-Aminolevulinic acid	3p21.1	2.3.1.37	125290	none
ALA dehydratase	D-Aminolevulinic acid	Porphobilinogen	9q34	4.2.1.24	125270	ALA-Dehydratase deficiency
PBG deaminase	Porphobilinogen	Hydroxymethyl bilane	11q23.3	2.5.1.61	176000	acute intermittent porphyria
Uroporphyrinogen III synthase	Hydroxymethyl bilane	Uroporphyrinogen III	10q25.2-q26.3	4.2.1.75	606938	congenital erythropoietic porphyria
Uroporphyrinogen III decarboxylase	Uroporphyrinogen III	Coproporphyrinogen III	1q34	4.1.1.37	176100	porphyria cutanea tarda
Coproporphyrinogen III oxidase	Coproporphyrinogen III	Protoporphyrinogen IX	3q12	1.3.3.3	121300	coproporphyria
Protoporphyrinogen oxidase	Protoporphyrinogen IX	Protoporphyrin IX	1q22	1.3.3.4	600923	variegate porphyria
Ferrochelatase	Protoporphyrin IX	Heme	18q21.3	4.99.1.1	177000	erythropoietic protoporphyria

Applications

Although natural porphyin complexes are essential for life, synthetic porphyrins and their complexes have limited utility. Complexes of meso-tetraphenylporphyrin, e.g., the iron-(III) chloride complex (TPPFeCl) catalyse a variety of reactions in organic chemistry, but none is of practical value. Porphyrin-based compounds are of interest in molecular electronics and supramolecular building blocks. Phthalocyanines, which are structurally related to porphyrins, are used in commerce as dyes and catalysts. Synthetic porphyrin dyes that are incorporated in the design of solar cells are the subject of ongoing research. See Dye-sensitized solar cells.

In 2008 the UK corporation Destiny Pharma reported successful clinical trials of an intranasally applied porphorin XF-73 against methicillin-resistant Staphylococcus aureus.

Supramolecular chemistry

Porphyrins are often used to construct structures in supramolecular chemistry. These systems take advantage of the Lewis acidity of the metal, typically zinc. An example of a host-guest complex that was constructed from a macrocycle composed of four porphyrins. A guest-free base porphyrin is bound to the center by coordination with its four pyridine sustituents.