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Porphyrin

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Structure of porphine, the simplest porphyrin.
Space-filling model of porphyrin

A porphyrin is a heterocyclic macrocycle derived from four pyrroline subunits interconnected via 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 which are delocalized over the macrocycle. The macrocycle, therefore, is a highly-conjugated system, and, as a consequence, is deeply coloured - the name porphyrin comes from a Greek word for purple. The macrocycle has 22 pi electrons. The parent porphyrin is porphine, and substituted porphines are called porphyrins. Many porphyrins occur in nature, such as in green leaves and red blood cells, and in bio-inspired synthetic catalysts and devices.

Porphyrins bind metals to form complexes. The metal ion, usually with a charge of 2+ or 3+, resides in the central N4 cavity formed by the loss of two protons. Most metals can be inserted. A schematic equation for these syntheses is shown:

H2porphyrin + [MLn]2+ → M(porphyrinate)Ln-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, that contain more hydrogen, than porphyrins, featuring 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

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 Alder and Longo.[3] The synthesis of simple porphyrins such as meso-tetraphenylporphyrin 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 porphyin 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) catalyse 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 intranasally applied porphorin XF-73 against methicillin-resistant Staphylococcus aureus.[5][6]

Supramolecular chemistry

File:Sanders AngewChemIntEdEngl 1995 1096.jpg
An example of a porphyrins involved in host-guest chemistry reported by Sanders and coworkers in Angew. Chem., Int. Ed. Engl. 1995, 34, 1096-1099.

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

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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Falvo, RaeAnne E.; Mink, Larry M.; Marsh, Diane F. "Microscale Synthesis and 1H NMR Analysis of Tetraphenylporphyrins". J. Chem. Educ. 1999 (76): 237.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ http://www.destinypharma.com/xf73.shtml
  6. ^ http://news.bbc.co.uk/2/hi/health/7406832.stm
  7. ^ Sanders and coworkers in Angew. Chem., Int. Ed. Engl. 1995, 34, 1096-1099.
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