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.
- H2porphyrin + [MLn]2+ → M(porphyrinate)Ln-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.
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:
Enzyme Location Substrate Product Chromosome EC OMIM Porphyria ALA synthase Mitochondrion Glycine, succinyl CoA δ-Aminolevulinic acid 3p21.1 22.214.171.124 125290 none ALA dehydratase Cytosol δ-Aminolevulinic acid Porphobilinogen 9q34 126.96.36.199 125270 ALA-Dehydratase deficiency PBG deaminase Cytosol Porphobilinogen Hydroxymethyl bilane 11q23.3 188.8.131.52 176000 acute intermittent porphyria Uroporphyrinogen III synthase Cytosol Hydroxymethyl bilane Uroporphyrinogen III 10q25.2-q26.3 184.108.40.206 606938 congenital erythropoietic porphyria Uroporphyrinogen III decarboxylase Cytosol Uroporphyrinogen III Coproporphyrinogen III 1p34 220.127.116.11 176100 porphyria cutanea tarda Coproporphyrinogen III oxidase Mitochondrion Coproporphyrinogen III Protoporphyrinogen IX 3q12 18.104.22.168 121300 coproporphyria Protoporphyrinogen oxidase Mitochondrion Protoporphyrinogen IX Protoporphyrin IX 1q22 22.214.171.124 600923 variegate porphyria Ferrochelatase Mitochondrion Protoporphyrin IX Heme 18q21.3 126.96.36.199 177000 erythropoietic protoporphyria
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 Adler and Longo. The synthesis of simple porphyrins such as meso-tetraphenylporphyrin (H2TPP) is also commonly done in university teaching labs.
The Rothemund synthesis is an condensation and oxidation starting with pyrrole and an aldehyde. In solution-phase synthesis, acidic conditions are essential; 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 or at high temperature in the gas phase. In these cases, no additional acid is required.
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.)
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 substituents.
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. On the other hand, nickel and vanadyl porphyrins could be related to catalytic molecules from bacteria that feed primordial hydrocarbons.
- 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
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- ^ 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.
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- ^ 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.
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- ^ 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.
- Journal of Porphyrins and Phthalocyanines
- Handbook of Porphyrin Science
- Porphynet - an informative site about porphyrins and related structures
Types of tetrapyrroles Bilanes
porphyrinsPorphyrinogensIsobacteriochlorinsSiroheme · SirohydrochlorinCorphins
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