Porphyrin

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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 carbon atoms via methine bridges (=CH-). Porphyrins are aromatic. That is, they obey Hckel's rule for aromaticity, possessing 4n+2 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.

Contents
1 Complexes of porphyrins and related molecules 2 Synthesis 2.1 Biosynthesis 2.2 Laboratory synthesis 3 Applications 3.1 Supramolecular chemistry 3.2 Organic geochemistry 4 See also 5 Gallery 6 References 7 External links

Structure of porphine, the simplest porphyrin

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

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 O 2-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 Hckel's rule, but most do not.

Synthesis
Biosynthesis
The "committed step" for porphyrin biosynthesis is the formation of D-aminolevulinic acid (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 synthesisnote that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)

Enzyme ALA synthase

Location Mitochondrion

substrate Glycine, succinyl CoA D-Aminolevulinic acid

Product D-Aminolevulinic acid Porphobilinogen

Chromosome EC 3p21.1

OMIM

porp

2.3.1.37 125290 (http://www.expasy.org/cgi- (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi? none bin/nicezyme.pl?2.3.1.37) id=125290) 4.2.1.24 125270 ALA (http://www.expasy.org/cgi- (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi? Deh defic bin/nicezyme.pl?4.2.1.24) id=125270) 2.5.1.61 176000 acut (http://www.expasy.org/cgi- (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi? inter porp bin/nicezyme.pl?2.5.1.61) id=176000) 4.2.1.75 606938 cong (http://www.expasy.org/cgi- (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi? eryth porp bin/nicezyme.pl?4.2.1.75) id=606938) 4.1.1.37 176100 porp (http://www.expasy.org/cgi- (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi? cuta bin/nicezyme.pl?4.1.1.37) id=176100) 1.3.3.3 121300 (http://www.expasy.org/cgi- (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi? copr bin/nicezyme.pl?1.3.3.3) id=121300) 1.3.3.4 600923 varie (http://www.expasy.org/cgi- (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi? porp bin/nicezyme.pl?1.3.3.4) id=600923) 4.99.1.1 177000 eryth (http://www.expasy.org/cgi- (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi? prot bin/nicezyme.pl?4.99.1.1) id=177000)

ALA dehydratase

Cytosol

9q34

PBG deaminase Uroporphyrinogen III synthase Uroporphyrinogen III decarboxylase

Cytosol

Porphobilinogen Hydroxymethyl bilane Uroporphyrinogen III

Hydroxymethyl bilane Uroporphyrinogen III

11q23.3 10q25.2q26.3

Cytosol

Cytosol

Coproporphyrinogen 1p34 III

Coproporphyrinogen Coproporphyrinogen Protoporphyrinogen Mitochondrion 3q12 III oxidase III IX Protoporphyrinogen Protoporphyrinogen Mitochondrion Protoporphyrin IX oxidase IX Ferrochelatase Mitochondrion Protoporphyrin IX Heme 1q22

18q21.3

Laboratory synthesis
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] It can be done by heating an equimolar mixture of pyrrole and benzaldehyde in refluxing propionic acid for about an hour. In this method (the Rothemund synthesis) 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 recrystallization or chromatography.

Brilliant crystals of mesotetratolylporphyrin, prepared from 4methylbenzaldehyde and pyrrole in refluxing propionic acid

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.[5]

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.[6] 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
An example of a porphyrins involved in host-guest chemistry. Here, a fourporphyrin-zinc complex hosts a porphyrin guest. [6]

Lewis structure for mesotetraphenylporphyrin

UV-vis readout for mesotetraphenylporphyrin

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): 625627. doi:10.1021/ja01295a027 (http://dx.doi.org/10.1021%2Fja01295a027) . 2. ^ P. Rothemund (1935). "Formation of Porphyrins from Pyrrole and Aldehydes". J. Am. Chem. Soc. 57 (10): 20102011. doi:10.1021/ja01313a510 (http://dx.doi.org/10.1021%2Fja01313a510) . 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): 476476. doi:10.1021/jo01288a053 (http://dx.doi.org/10.1021%2Fjo01288a053) . 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. ^ "Hope for new way to destroy MRSA" (http://news.bbc.co.uk/2/hi/health/7406832.stm) . BBC News. 2008-05-23. http://news.bbc.co.uk/2/hi/health/7406832.stm. Retrieved 2010-05-22. 6. ^ 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: 10961099. doi:10.1002/anie.199510961 (http://dx.doi.org/10.1002%2Fanie.199510961) .

External links
Journal of Porphyrins and Phthalocyanines (http://www.worldscinet.com/jpp/) Handbook of Porphyrin Science (http://www.worldscibooks.com/chemistry/7376.html) Porphynet - an informative site about porphyrins and related structures (http://www.porphyrin.net) Retrieved from "http://en.wikipedia.org/wiki/Porphyrin" Categories: Biomolecules | Metabolism | Photosynthesis | Supramolecular chemistry | Chelating agents | Tetrapyrroles | Macrocycles This page was last modified on 23 July 2011 at 18:57. Text is available under the Creative Commons Attribution-ShareAlike License; additional terms may apply. See Terms of use for details. Wikipedia is a registered trademark of the Wikimedia Foundation, Inc., a non-profit organization.