porphyrin

Any of various organic compounds containing four pyrrole rings, occurring universally in protoplasm, and functioning as a metal-binding cofactor in hemoglobin, chlorophyll, and certain enzymes.

[Greek porphurā, shellfish yielding purple dye, purple + –IN.]

What made King Geoge III so very mad? The British ruler who presided over the loss of the American colonies in 1776 was diagnosed about two centuries too late with porphyria — a genetic disorder that causes psychiatric disturbances, among other things — and more recently researchers found arsenic in his hair (presumably from contaminated medication), which may have made him even madder:

"'It is extremely likely that his bouts of madness were due to severe porphyric attacks,' [biochemist Martin J.] Warren said. 'Arsenic may have precipitated his attacks, or made them much more severe.'"

Link: Arsenic Is Linked to British King's Episodes of Madness

Posted July 24, 2005.

See our Word Overheard blog to see interesting uses of strange words.

One of a class of cyclic compounds in which the parent macrocycle consists of four pyrrole-type units linked together by single carbon bridges. Several porphyrins with selected peripheral substitution and metal coordination carry out vital biochemical processes in living organisms. Chlorins, bacteriochlorins, and corrins (see structures) are related tetrapyrrolic macrocycles that are also observed in biologically important compounds.

The complexity of porphyrin nomenclature parallels the complex structures of the naturally occurring derivatives. Hans Fischer used a simple numbering system for the porphyrin nucleus (see structures) and a set of common names to identify the different porphyrins and their isomers. A systematic naming based on the 1–24 numbering system for the porphyrin nucleus was later developed by the International Union of Pure and Applied Chemistry (IUPAC) and the International Union of Biochemistry (IUB), and this system has gained general acceptance. The need for common names is clear after examination of the systematic names; for example, protoporphyrin IX has the systematic name 2,7,12,18-tetramethyl-3,8-divinyl-13,17-dipropanoic acid.

The aromatic character (hence stability) of porphyrins has been confirmed by measurements of their heats of combustion. In addition, x-ray crystallographic studies have established planarity of the porphyrin macrocycle which is a basic requirement for aromatic character. See also Delocalization.

Most metals and metalloids have been inserted into the central hole of the porphyrin macrocycle. The resulting metalloporphyrins are usually very stable and can bind a variety of small molecules (known as ligands) to the central metal atom. Heme, the iron complex of protoporphyrin IX, is the prosthetic group of a number of major proteins and enzymes that carry out diverse biological functions. These include binding, transport, and storage of oxygen (hemoglobin and myoglobin), electron-transfer processes (cytochromes), activation and transfer of oxygen to substrates (cytochromes P450), and managing and using hydrogen peroxide (peroxidases and catalases). See also Coordination complexes; Cytochrome.

Chlorophylls and bacteriochlorophylls are magnesium complexes of porphyrin derivatives known as chlorins and bacteriochlorins, respectively. They are the pigments responsible for photosynthesis. Several chlorophylls have been identified, the most common being chlorophyll a, which is found in all oxygen-evolving photosynthetic plants. Bacteriochlorophyll a is found in many photosynthetic bacteria.

Porphyrins and metalloporphyrins exhibit many potentially important medicinal and industrial properties. Metalloporphyrins are being examined as potential catalysts for a variety of processes, including catalytic oxidations. They are also being examined as possible blood substitutes and as electrocatalysts for fuel cells and for the electrochemical generation of hydrogen peroxide. The unique optical properties of porphyrins make them likely candidates for photovoltaic devices and in photocopying and other optical devices. A major area where porphyrins are showing significant potential is in the treatment of a wide range of diseases, including cancer, using photodynamic therapy. See also Catalysis.

Any iron or magnesium-free pyrrole derivative occurring in many plant and animal tissues. Normal findings of porphyrins in urine are 60 mg to 200 mg/24-hour period.

For more information on porphyrin, visit Britannica.com.

A class of pigments containing pyrolle rings and a metal. Porphyrins include the iron-containing haemoglobin, myoglobin, and cytochromes, and the magnesium-containing chlorophyll.

Any of a group of iron- or magnesium-free cyclic tetrapyrrole derivatives which forms the basis of the respiratory pigments of animals and plants. Porphyrins, in combination with iron, form hemes.

• p. test — the presence of porphyrin in cultures of Hemophilus spp. or Tayorella equigenitalis indicates that hemin is not required for growth.

Structure of porphine, the simplest porphyrin.

Space-filling model of porphyrin

Porphyrins are a group of organic compounds of which many occur in nature, most famously as the pigment in red blood cells. They are heterocyclic macrocycles characterised by the presence of four modified pyrrole subunits interconnected at 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 that are delocalized over the macrocycle. The macrocycles, therefore, are highly-conjugated system and consequently are deeply colored - the name porphyrin comes from a Greek word for purple. The macrocycle has 26 pi electrons. The parent porphyrin is porphine, and substituted porphines are called porphyrins.

Contents 1 Complexes of porphyrins and related molecules 2 Laboratory synthesis 3 Biosynthesis 4 Applications 5 Supramolecular chemistry 6 See also 7 Gallery 8 References 9 External links

Complexes of porphyrins and related molecules

Porphyrins are the conjugate acids of ligands that bind metals to form complexes. The metal ion, usually with a charge of 2+ or 3+. 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, contain more hydrogen than porphyrins, and feature 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

Brilliant crystals of meso-tetratolylporphyrin, prepared from 4-methylbenzaldehyde and pyrrole in refluxing propionic acid.

One of the more common syntheses for porphyrins is based on work by Paul Rothemund.^[1][2] His techniques underpin more modern syntheses such as those described by Adler and Longo.^[3] The synthesis of simple porphyrins such as meso-tetraphenylporphyrin (H₂TPP) is also commonly done in university teaching labs.^[4]

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:

Heme synthesis—note that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)

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 porphyrin 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) catalyses 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 intra-nasally applied porphyrin XF-73 against methicillin-resistant Staphylococcus aureus.^[5][6]

Supramolecular chemistry

An example of a porphyrins involved in host-guest chemistry reported by Sanders et al..^[7]

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.^[7] A guest-free base porphyrin is bound to the center by coordination with its four pyridine sustituents.

See also

• A porphyrin-related disease: porphyria
• Porphyrin coordinated to iron: heme
• Porphyrin coordinated to magnesium: chlorophyll
• The one-carbon-shorter analogues: corroles, including Vitamin B12 which is coordinated to a cobalt
• Corphins, the highly-reduced porphyrin coordinated to nickel that binds the F430 active site in methyl coenzyme M reductase (MCR)
• Nitrogen-substituted porphyrins: phthalocyanine

Gallery

Lewis structure for meso-tetraphenylporphyrin

UV-vis readout for meso-tetraphenylporphyrin

References

1. ^ P. Rothemund (1936). "A New Porphyrin Synthesis. The Synthesis of Porphin". J. Am. Chem. Soc. 58 (4): 625–627. doi:10.1021/ja01295a027. 
2. ^ P. Rothemund (1935). "Formation of Porphyrins from Pyrrole and Aldehydes". J. Am. Chem. Soc. 57 (10): 2010–2011. doi:10.1021/ja01313a510. 
3. ^ A. D. Adler, F. R. Longo, J. D. Finarelli, J. Goldmacher, J. Assour and L. Korsakoff (1967). "A simplified synthesis for meso-tetraphenylporphine". J. Org. Chem. 32 (2): 476–476. doi:10.1021/jo01288a053. 
4. ^ Falvo, RaeAnne E.; Mink, Larry M.; Marsh, Diane F.. "Microscale Synthesis and ¹H NMR Analysis of Tetraphenylporphyrins". J. Chem. Educ. 1999 (76): 237. 
5. ^ Destiny Pharma - XF-73
6. ^ BBC NEWS | Health | Hope for new way to destroy MRSA
7. ^ ^{a b} Sally Anderson, Harry L. Anderson, Alan Bashall, Mary McPartlin, Jeremy K. M. Sanders (1995). "Assembly and Crystal Structure of a Photoactive Array of Five Porphyrins". Angew. Chem., Int. Ed. Engl. 34: 1096–1099. doi:10.1002/anie.199510961. 

External links

• Journal of Porphyrins and Phthalocyanines
• Handbook of Porphyrin Science
• Porphynet - an informative site about porphyrins and related structures

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