Porphyrin

Structure of porphine, the simplest porphyrin

Heme group of hemoglobin. An iron (Fe) atom in the middle is shown in red, complexed to four interior nitrogen atoms shown in blue.

Porphyrins are a group of organic compounds, many naturally occurring. One of the best-known porphyrins is heme, the pigment in red blood cells; heme is a cofactor of the protein hemoglobin. Porphyrins are heterocyclic macrocycles composed of four modified pyrrole subunits interconnected at their α carbon atoms via methine bridges (=CH-). Porphyrins are aromatic. That is, they obey Hückel's rule for aromaticity, possessing 4n+2 π electrons (n=4 for the shortest cyclic path) delocalized over the macrocycle. Thus porphyrin macrocycles are highly conjugated systems. As a consequence, they typically have very intense absorption bands in the visible region and may be deeply colored; the name porphyrin comes from a Greek word for purple. The macrocycle has 26 pi electrons in total. The parent porphyrin is porphine, and substituted porphines are called porphyrins.

Complexes of porphyrins and related molecules

Porphyrins are the conjugate acids of ligands that bind metals to form complexes. The metal ion usually has 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⁺ where M=metal ion and L=a ligand

A porphyrin without metal in its cavity is a free base. Some iron-containing porphyrins are called hemes. Heme-containing proteins, or hemoproteins, are found extensively in nature. Hemoglobin and myoglobin are two O₂-binding proteins that contain iron porphyrins. Various cytochromes are also hemoproteins.

Several other heterocycles are related to porphyrins. These include 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 a chlorophyll molecule. 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.

Synthesis

Biosynthesis

The "committed step" for porphyrin biosynthesis is the formation of δ-aminolevulinic acid (δ-ALA, 5-ALA or dALA) by the reaction of the amino acid glycine with 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)

Heme B biosynthesis pathway and its modulators. Major enzyme deficiences are also shown here.

Enzyme	Location	Substrate	Product	Chromosome	EC	OMIM	Porphyria
ALA synthase	Mitochondrion	Glycine, succinyl CoA	δ-Aminolevulinic acid	3p21.1	2.3.1.37	125290	none
ALA dehydratase	Cytosol	δ-Aminolevulinic acid	Porphobilinogen	9q34	4.2.1.24	125270	ALA-Dehydratase deficiency
PBG deaminase	Cytosol	Porphobilinogen	Hydroxymethyl bilane	11q23.3	2.5.1.61	176000	acute intermittent porphyria
Uroporphyrinogen III synthase	Cytosol	Hydroxymethyl bilane	Uroporphyrinogen III	10q25.2-q26.3	4.2.1.75	606938	congenital erythropoietic porphyria
Uroporphyrinogen III decarboxylase	Cytosol	Uroporphyrinogen III	Coproporphyrinogen III	1p34	4.1.1.37	176100	porphyria cutanea tarda
Coproporphyrinogen III oxidase	Mitochondrion	Coproporphyrinogen III	Protoporphyrinogen IX	3q12	1.3.3.3	121300	coproporphyria
Protoporphyrinogen oxidase	Mitochondrion	Protoporphyrinogen IX	Protoporphyrin IX	1q22	1.3.3.4	600923	variegate porphyria
Ferrochelatase	Mitochondrion	Protoporphyrin IX	Heme	18q21.3	4.99.1.1	177000	erythropoietic protoporphyria

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]

The Rothemund synthesis is an condensation and oxidation starting with pyrrole and an aldehyde. In solution-phase synthesis, acidic conditions are essential;^{[citation needed]} formic acid, acetic acid, and propionic acid are typical reaction solvents, or p-toluenesulfonic acid or various Lewis acids can be used with a non-acidic solvent. A large amount of side-product is formed and is removed, usually by recrystallization or chromatography.

Modern green chemistry variants have been developed in which the reaction is performed adsorbed on acidic silica gel with microwave irradiation^[5] or at high temperature in the gas phase.^[6] In these cases, no additional acid is required.

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), catalyze a variety of reactions in organic synthesis, but none of them are 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 corporation Destiny Pharma Ltd reported successful clinical trials of an intra-nasally applied porphyrin XF-73 against methicillin-resistant Staphylococcus aureus.^[7]

Supramolecular chemistry

An example of a porphyrins involved in host-guest chemistry. Here, a four-porphyrin-zinc complex hosts a porphyrin guest.^[8]

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.^[8] A guest-free base porphyrin is bound to the center by coordination with its four-pyridine substituents.

Organic geochemistry

The field of organic geochemistry, the study of the impacts and processes that organisms have had on the Earth, had its origins in the isolation of porphyrins from petroleum. This finding helped establish the biological origins of petroleum. Petroleum is sometimes "fingerprinted" by analysis of trace amounts of nickel and vanadyl porphyrins.

Chlorophyll is a magnesium porphyrin, and heme is an iron porphyrin, but neither porphyrin is present in petroleum.^{[citation needed]} On the other hand, nickel and vanadyl porphyrins could be related to catalytic molecules from bacteria that feed primordial hydrocarbons.

See also

• A porphyrin-related disease: porphyria
• Porphyrin coordinated to iron: heme
• A heme-containing group of enzymes: Cytochrome P450
• 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

• 

  Light-activated porphyrin. Monatomic oxygen. Cellular aging

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): 237–239. doi:10.1021/ed076p237. 
5. ^ Petit, A.; Loupy, A.; Maiuard, P.; Momenteau, M. (1992). Synth. Commun. 22 (8): 1137–1142. doi:10.1080/00397919208021097. 
6. ^ Drain, C. M.; Gong, X. (1997). "Synthesis of meso substituted porphyrins in air without solvents or catalysts". Chem. Commun.: 2117–2118. doi:10.1039/A704600F. 
7. ^ "Hope for new way to destroy MRSA". BBC News. 2008-05-23. http://news.bbc.co.uk/2/hi/health/7406832.stm. Retrieved 2010-05-22. 
8. ^ ^{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