Porphyrins ( ) are heterocyclic, macrocyclic, , composed of four modified pyrrole subunits interconnected at their α carbon atoms via methine bridges (). In , an essential member of the porphyrin group is heme, which is a component of , whose functions include carrying oxygen in the bloodstream. In plants, an essential porphyrin derivative is chlorophyll, which is involved in light harvesting and electron transfer in photosynthesis.
The parent of porphyrins is porphine, a rare chemical compound of exclusively theoretical interest. Substituted porphines are called porphyrins.
Structure
Porphyrin complexes consist of a square planar MN
4 core. The periphery of the porphyrins, consisting of sp
2-hybridized carbons, generally display small deviations from planarity. "Ruffled" or saddle-shaped porphyrins is attributed to interactions of the system with its environment.
Additionally, the metal is often not centered in the N
4 plane.
For free porphyrins, the two pyrrole protons are mutually trans and project out of the N
4 plane.
[ ] These nonplanar distortions are associated with altered chemical and physical properties.
Chlorophyll-rings are more distinctly nonplanar, but they are more saturated than porphyrins.
Complexes of porphyrins
Concomitant with the displacement of two N-
H protons, porphyrins bind metal ions in the N4 "pocket". The metal
ion usually has a charge of 2+ or 3+. A schematic equation for these syntheses is shown, where M = metal ion and L = a
ligand:
File:PPIXtransH.png|Derivatives of protoporphyrin IX are common in nature, the precursor to .
File:H2octaethylporphyrin.png |Octaethylporphyrin (H2OEP) is a synthetic analogue of protoporphyrin IX. Unlike the natural porphyrin ligands, OEP2− is highly symmetrical.
File:H2TPP.png|Tetraphenylporphyrin (H2TPP)is another synthetic analogue of protoporphyrin IX. Unlike the natural porphyrin ligands, TPP2− is highly symmetrical. Another difference is that its methyne centers are occupied by phenyl groups.
File:Heme B.svg|Simplified view of heme, a complex of a protoporphyrin IX.
CP40model.png|A nanoring of 40 porphyrin molecules, model
CP40-STM.png|A nanoring of 40 porphyrin molecules, STM image
Ancient porphyrins
A geoporphyrin, also known as a petroporphyrin, is a porphyrin of geologic origin.
They can occur in
crude oil,
oil shale, coal, or sedimentary rocks.
The field of organic geochemistry had its origins in the isolation of porphyrins from petroleum. These findings helped establish the biological origins of petroleum.[Kvenvolden, Keith A. (2006). "Organic geochemistry – A retrospective of its first 70 years". Organic Geochemistry. 37: 1–11. doi:10.1016/j.orggeochem.2005.09.001][Treibs, A.E. (1936). "Chlorophyll- und Häminderivate in organischen Mineralstoffen". Angewandte Chemie. 49: 682–686. doi:10.1002/ange.19360493803] Petroleum is sometimes "fingerprinted" by analysis of trace amounts of nickel and vanadyl porphyrins. Metalloporphyrins in general are highly stable organic compounds, and the detailed structures of the extracted derivatives made clear that they originated from chlorophyll.
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 hydrolysation 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:
|
| ALA synthase | Mitochondrion | Glycine, succinyl CoA | δ-Aminolevulinic acid | 3p21.1 | 2.3.1.37 | 125290 | X-linked dominant protoporphyria, X-linked sideroblastic anemia |
| ALA dehydratase | Cytosol | δ-Aminolevulinic acid | Porphobilinogen | 9q34 | 4.2.1.24 | 125270 | aminolevulinic acid dehydratase deficiency porphyria |
| 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, hepatoerythropoietic porphyria |
| Coproporphyrinogen III oxidase | Mitochondrion | Coproporphyrinogen III | Protoporphyrinogen IX | 3q12 | 1.3.3.3 | 121300 | hereditary 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
A common synthesis for porphyrins is the Rothemund reaction, first reported in 1936,
Potential applications
Photodynamic therapy
Porphyrins have been evaluated in the context of photodynamic therapy (PDT) since they strongly absorb light, which is then converted to heat in the illuminated areas.
PDT is considered a noninvasive cancer treatment, involving the interaction between light of a determined frequency, a photo-sensitizer, and oxygen. This interaction produces the formation of a highly reactive oxygen species (ROS), usually singlet oxygen, as well as superoxide anion, free hydroxyl radical, or hydrogen peroxide.
Molecular electronics and sensors
Porphyrin-based compounds are of interest as possible components of molecular electronics and photonics.
Biological applications
Porphyrins have been investigated as possible anti-inflammatory agents
Toxicology
Heme biosynthesis is used as biomarker in environmental toxicology studies. While excess production of porphyrins indicate organochlorine exposure, lead inhibits ALA dehydratase enzyme.
Gallery
File:H2TPP.png|Lewis structure for meso-tetraphenylporphyrin
File:Meso-tetraphenylporphyrin UV-vis.JPG|UV–vis readout for meso-tetraphenylporphyrin
File:Porfirina activada con la luz.svg|Light-activated porphyrin. Monatomic oxygen. Cellular aging
Related species
In nature
Several heterocycles related to porphyrins are found in nature, almost always bound to metal ions. These include
|
| several versions of chlorophyll exist (sidechain; exception being chlorophyll c) |
| several versions of bacteriochlorophyll exist (sidechain; some use a usual chlorin ring) |
| Important cofactor in sulfur assimilation |
| | | biosynthetic intermediate en route to cofactor F430 and B12 |
| several variants of B12 exist (sidechain) |
| highly reduced macrocycle |
Synthetic
A benzoporphyrin is a porphyrin with a benzene ring fused to one of the pyrrole units. e.g. verteporfin is a benzoporphyrin derivative.
Non-natural porphyrin isomers
The first synthetic porphyrin isomer was reported by Emanual Vogel and coworkers in 1986.
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: , including vitamin B12, which is coordinated to a cobalt
-
Corphins, the highly reduced porphyrin coordinated to nickel that binds the Cofactor F430 active site in methyl coenzyme M reductase (MCR)
-
Nitrogen-substituted porphyrins: phthalocyanine, tetrapyrazinoporphyrazine
-
Extended porphyrins: tetraanthraporphyrin
External links
