Porphyrin

Not to be confused with Perforin.
Structure of porphine, the simplest porphyrin
Heme B 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 heterocyclic macrocycle organic compounds, composed of four modified pyrrole subunits interconnected at their α carbon atoms via methine bridges (=CH−). The parent porphyrin is porphin, and substituted porphines are called porphyrins. The porphyrin macrocycle has 26 (delocalized) pi electrons in total, therefore by Hückel's rule it is aromatic, possessing 4n+2 π electrons (n=4, for the shortest cyclic path). Thus porphyrin macrocycles are highly conjugated systems and consequently they typically have very intense absorption bands in the visible region and may be deeply colored; the name "porphyrin" comes from the Greek word porphyros, meaning purple.[1]

Many porphyrins are naturally occurring; one of the best-known porphyrins is heme, the pigment in red blood cells, a cofactor of the protein hemoglobin. (The specific porphyrin in heme B (see Figure) is called protoporphyrin IX and has 4 methyl, two vinyl, and two propionic acid substituents at the indicated positions.)

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 + [MLn]2+ → M(porphyrinate)Ln−4 + 4 L + 2 H+ where M = metal ion and L = a ligand

A porphyrin without a metal-ion 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.

Natural formation

A geoporphyrin, also known as a petroporphyrin, is a porphyrin of geologic origin.[2] They can occur in crude oil, oil shale, coal, or sedimentary rocks.[2][3] Abelsonite is possibly the only geoporphyrin mineral, as it is rare for porphyrins to occur in isolation and form crystals.[4]

Synthesis

Biosynthesis

In non-photosynthetic eukaryotes such as animals, insects, fungi, and protozoa, as well as the α-proteobacteria group of bacteria, 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. In plants, algae, bacteria (except for the α-proteobacteria group) and archaea, it is produced from glutamic acid via glutamyl-tRNA and glutamate-1-semialdehyde. The enzymes involved in this pathway are glutamyl-tRNA synthetase, glutamyl-tRNA reductase, and glutamate-1-semialdehyde 2,1-aminomutase. This pathway is known as the C5 or Beale pathway.

Two molecules of dALA are then combined by porphobilinogen synthase 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 B biosynthesis pathway and its modulators. Major enzyme deficiences are also shown.
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 most common syntheses for porphyrins is based on work by Paul Rothemund.[5][6] His techniques underpin more modern synthesis such as those described by Adler and Longo.[7] The synthesis of simple porphyrins such as meso-tetraphenylporphyrin (H2TPP) is also commonly done in university teaching labs.[8]

The Rothemund synthesis is a 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.

Green chemistry variants have been developed in which the reaction is performed with microwave irradiation using reactants adsorbed on acidic silica gel[9] or at high temperature in the gas phase.[10] In these cases, no additional acid is required.

Applications

The main role of porphyrins is their support of aerobic life. Complexes of meso-tetraphenylporphyrin, e.g., the iron(III) chloride complex (TPPFeCl), catalyze a variety of reactions of potential interest in organic synthesis.

Medicine

Porphyrins have been evaluated in the context of photodynamic therapy since they strongly absorb light, which is then converted to energy and heat in the illuminated areas. This has been applied in macular degeneration using verteporfin.[11]

Molecular electronics

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. Recent applications of porphyrin dyes for dye-sensitized solar cells have shown solar conversion efficiencies approaching silicon based photovoltaic devices.[12][13]

Supramolecular chemistry

An example of a porphyrins involved in host–guest chemistry. Here, a four-porphyrin–zinc complex hosts a porphyrin guest.[14]

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.[14] 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. On the other hand, nickel and vanadyl porphyrins could be related to catalytic molecules from bacteria that feed primordial hydrocarbons.

See also

Gallery

References

  1. ↑ Harper, Douglas; Buglione, Drew Carey. "porphyria (n.)". The Online Etymology Dictionary. Retrieved 14 September 2014.
  2. ↑ 2.0 2.1 Karl M. Kadish (ed.). The Porphyrin Handbook. Elsevier. p. 381. ISBN 9780123932006.
  3. ↑ Zhang, Bo; Lash, Timothy D. (September 2003). "Total synthesis of the porphyrin mineral abelsonite and related petroporphyrins with five-membered exocyclic rings". Tetrahedron Letters 44 (39): 7253. doi:10.1016/j.tetlet.2003.08.007.
  4. ↑ Mason, G. M.; Trudell, L. G.; Branthaver, J. F. (1989). "Review of the stratigraphic distribution and diagenetic history of abelsonite". Organic Geochemistry 14 (6): 585. doi:10.1016/0146-6380(89)90038-7.
  5. ↑ P. Rothemund (1936). "A New Porphyrin Synthesis. The Synthesis of Porphin". J. Am. Chem. Soc. 58 (4): 625–627. doi:10.1021/ja01295a027.
  6. ↑ P. Rothemund (1935). "Formation of Porphyrins from Pyrrole and Aldehydes". J. Am. Chem. Soc. 57 (10): 2010–2011. doi:10.1021/ja01313a510.
  7. ↑ 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.
  8. ↑ Falvo, RaeAnne E.; Mink, Larry M.; Marsh, Diane F. (1999). "Microscale Synthesis and 1H NMR Analysis of Tetraphenylporphyrins". J. Chem. Educ. 1999 (76): 237–239. doi:10.1021/ed076p237.
  9. ↑ Petit, A.; Loupy, A.; Maiuard, P.; Momenteau, M. (1992). "Microwave Irradiation in Dry Media: A New and Easy Method for Synthesis of Tetrapyrrolic Compounds". Synth. Commun. 22 (8): 1137–1142. doi:10.1080/00397919208021097.
  10. ↑ Drain, C. M.; Gong, X. (1997). "Synthesis of meso substituted porphyrins in air without solvents or catalysts". Chem. Commun. (21): 2117–2118. doi:10.1039/A704600F.
  11. ↑ Wormald R, Evans J, Smeeth L, Henshaw K (2007). "Photodynamic therapy for neovascular age-related macular degeneration". Cochrane Database Syst Rev (3): CD002030. doi:10.1002/14651858.CD002030.pub3. PMID 17636693.
  12. ↑ Michael G. Walter, Alexander B. Rudine, Carl C. Wamser (2010). "Porphyrins and phthalocyanines in solar photovoltaic cells". Journal of Porphyrins and Phthalocyanines 14 (9): 759–792. doi:10.1142/S1088424610002689. http://www.worldscinet.com/jpp/14/1409/S1088424610002689.html
  13. ↑ Aswani Yella, Hsuan-Wei Lee, Hoi Nok Tsao, Chenyi Yi, Aravind Kumar Chandiran, Md.Khaja Nazeeruddin, Eric Wei-Guang Diau, Chen-Yu Yeh, Shaik M Zakeeruddin, Michael Grätzel (2011). "Porphyrin-Sensitized Solar Cells with Cobalt (II/III)–Based Redox Electrolyte Exceed 12 Percent Efficiency". Science 334 (6056): 629–634. Bibcode:2011Sci...334..629Y. doi:10.1126/science.1209688. http://www.sciencemag.org/content/334/6056/629.abstract
  14. ↑ 14.0 14.1 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 (10): 1096–1099. doi:10.1002/anie.199510961.

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