Porphyrin
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Porphyrins (Template:IPAc-en Template:Respell) are a group of heterocyclic, macrocyclic, organic compounds, composed of four modified pyrrole subunits interconnected at their α carbon atoms via methine bridges (Template:Chem2). In vertebrates, an essential member of the porphyrin group is heme, which is a component of hemoproteins, 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.<ref>Template:Cite journal</ref> With a total of 26 π-electrons the porphyrin ring structure is often described as aromatic.<ref>Template:Cite journal</ref> One result of the large conjugated system is that porphyrins absorb strongly in the visible region of the electromagnetic spectrum, i.e. they are deeply colored. The name "porphyrin" derives Template:Ety.<ref>Template:Cite web</ref>
Structure
[edit]Porphyrin complexes consist of a square planar MN4 core. The periphery of the porphyrins, consisting of sp2-hybridized carbons, generally display small deviations from planarity. "Ruffled" or saddle-shaped porphyrins is attributed to interactions of the system with its environment.<ref>Template:Cite journal</ref> Additionally, the metal is often not centered in the N4 plane.<ref>Template:Cite book</ref> For free porphyrins, the two pyrrole protons are mutually trans and project out of the N4 plane.<ref> Template:Cite journal</ref> These nonplanar distortions are associated with altered chemical and physical properties. Chlorophyll-rings are more distinctly nonplanar, but they are more saturated than porphyrins.<ref>Template:Cite journal</ref>
Complexes of porphyrins
[edit]Template:Main 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:
- Representative porphyrins and derivatives
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Derivatives of protoporphyrin IX are common in nature, the precursor to hemes.
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Octaethylporphyrin (H2OEP) is a synthetic analogue of protoporphyrin IX. Unlike the natural porphyrin ligands, OEP2− is highly symmetrical.
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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.
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Simplified view of heme, a complex of a protoporphyrin IX.
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A nanoring of 40 porphyrin molecules, model
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A nanoring of 40 porphyrin molecules, STM image
Ancient porphyrins
[edit]A geoporphyrin, also known as a petroporphyrin, is a porphyrin of geologic origin.<ref name=handbook>Template:Cite book</ref> They can occur in crude oil, oil shale, coal, or sedimentary rocks.<ref name=handbook/><ref>Template:Cite journal</ref> Abelsonite is possibly the only geoporphyrin mineral, as it is rare for porphyrins to occur in isolation and form crystals.<ref>Template:Cite journal</ref>
The field of organic geochemistry had its origins in the isolation of porphyrins from petroleum. These findings helped establish the biological origins of petroleum.<ref>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</ref><ref>Treibs, A.E. (1936). "Chlorophyll- und Häminderivate in organischen Mineralstoffen". Angewandte Chemie. 49: 682–686. doi:10.1002/ange.19360493803</ref> 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
[edit]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:
Laboratory synthesis
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A common synthesis for porphyrins is the Rothemund reaction, first reported in 1936,<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> which is also the basis for more recent methods described by Adler and Longo.<ref>Template:Cite journal</ref> The general scheme is a condensation and oxidation process starting with pyrrole and an aldehyde.
Potential applications
[edit]Photodynamic therapy
[edit]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.<ref>Template:Cite encyclopedia</ref> This technique has been applied in macular degeneration using verteporfin.<ref name="pmid17636693">Template:Cite journal</ref>
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.<ref>Template:Cite journal</ref> These high reactive oxygen species react with susceptible cellular organic biomolecules such as; lipids, aromatic amino acids, and nucleic acid heterocyclic bases, to produce oxidative radicals that damage the cell, possibly inducing apoptosis or even necrosis.<ref>Template:Cite journal</ref>
Molecular electronics and sensors
[edit]Porphyrin-based compounds are of interest as possible components of molecular electronics and photonics.<ref>Template:Cite journal</ref> Synthetic porphyrin dyes have been incorporated in prototype dye-sensitized solar cells.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
Biological applications
[edit]Porphyrins have been investigated as possible anti-inflammatory agents<ref>Template:Cite journal</ref> and evaluated on their anti-cancer and anti-oxidant activity.<ref>Template:Cite journal</ref> Several porphyrin-peptide conjugates were found to have antiviral activity against HIV in vitro.<ref>Template:Cite journal</ref>
Toxicology
[edit]Heme biosynthesis is used as biomarker in environmental toxicology studies. While excess production of porphyrins indicate organochlorine exposure, lead inhibits ALA dehydratase enzyme.<ref>Template:Cite book</ref>
Gallery
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Lewis structure for meso-tetraphenylporphyrin
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UV–vis readout for meso-tetraphenylporphyrin
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Light-activated porphyrin. Monatomic oxygen. Cellular aging
Related species
[edit]In nature
[edit]Several heterocycles related to porphyrins are found in nature, almost always bound to metal ions. These include
| N4-macrocycle | Cofactor name | metal | comment |
|---|---|---|---|
| chlorin | chlorophyll | magnesium | several versions of chlorophyll exist (sidechain; exception being chlorophyll c) |
| bacteriochlorin | bacteriochlorophyll (in part) | magnesium | several versions of bacteriochlorophyll exist (sidechain; some use a usual chlorin ring) |
| sirohydrochlorin (an isobacteriochlorin) | siroheme | iron | Important cofactor in sulfur assimilation |
| biosynthetic intermediate en route to cofactor F430 and B12 | |||
| corrin | vitamin B12 | cobalt | several variants of B12 exist (sidechain) |
| corphin | Cofactor F430 | nickel | highly reduced macrocycle |
Synthetic
[edit]A benzoporphyrin is a porphyrin with a benzene ring fused to one of the pyrrole units. e.g. verteporfin is a benzoporphyrin derivative.<ref name=Scott2000>Template:Cite journal</ref>
Non-natural porphyrin isomers
[edit]The first synthetic porphyrin isomer was reported by Emanual Vogel and coworkers in 1986.<ref>Template:Cite journal</ref> This isomer [18]porphyrin-(2.0.2.0) is named as porphycene, and the central N4 Cavity forms a rectangle shape as shown in figure.<ref>Template:Cite journal</ref> Porphycenes showed interesting photophysical behavior and found versatile compound towards the photodynamic therapy.<ref>Template:Cite journal</ref> This result was followed by the preparation of [18]porphyrin-(2.1.0.1), named it as corrphycene or porphycerin.<ref>Template:Cite journal</ref> Other non-natural porphyrins include [18]porphyrin-(2.1.1.0) and [18]porphyrin-(3.0.1.0) or isoporphycene.<ref>Template:Cite journal</ref> The N-confused porphyrins feature one of the pyrrolic subunits with the nitrogen atoms facing outwards from the core of the macrocycle.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
See also
[edit]- 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 Cofactor F430 active site in methyl coenzyme M reductase (MCR)
- Nitrogen-substituted porphyrins: phthalocyanine, tetrapyrazinoporphyrazine