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Porphyrins ( ) are a group of
heterocyclic A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and ...
macrocycle
organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...
s, composed of four modified
pyrrole Pyrrole is a heterocyclic aromatic organic compound, a five-membered ring with the formula C4 H4 NH. It is a colorless volatile liquid that darkens readily upon exposure to air. Substituted derivatives are also called pyrroles, e.g., ''N''-meth ...
subunits interconnected at their α carbon atoms via
methine In organic chemistry, a methine group or methine bridge is a trivalent functional group , derived formally from methane. It consists of a carbon atom bound by two single bonds and one double bond, where one of the single bonds is to a hydro ...
bridges (=CH−). The parent of porphyrin is porphine, a rare chemical compound of exclusively theoretical interest. Substituted porphines are called porphyrins. With a total of 26 π-electrons, of which 18 π-electrons form a planar, continuous cycle, the porphyrin ring structure is often described as
aromatic In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satur ...
. One result of the large
conjugated system In theoretical chemistry, a conjugated system is a system of connected p-orbitals with delocalized electrons in a molecule, which in general lowers the overall energy of the molecule and increases stability. It is conventionally represented ...
is that porphyrins typically absorb strongly in the visible region of the electromagnetic spectrum, i.e. they are deeply colored. The name "porphyrin" derives from the
Greek Greek may refer to: Greece Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group. *Greek language, a branch of the Indo-European language family. **Proto-Greek language, the assumed last common ancestor ...
word πορφύρα (''porphyra''), meaning ''purple''.


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: :H2porphyrin + Lnsup>2+ → M(porphyrinate)Ln−4 + 4 L + 2 H+, where M = metal ion and L = a ligand The insertion of the metal center is slow in the absence of catalysts. In nature, these catalysts (enzymes) are called
chelatase In biochemistry, chelatases are enzymes that catalyze the insertion ("metalation") of naturally occurring tetrapyrroles. Many tetrapyrrole-based cofactors exist in nature including hemes, chlorophylls, and vitamin B12. These metallo cofactors are ...
s. When there is no metal ion (or atom) bound to the nitrogens in the center, then the compounds are called ''free porphine'' or ''free porphyrin''. If they are bonded to a metal in the center, then they are ''bound''. A porphyrin with an iron atom of the type found in
myoglobin Myoglobin (symbol Mb or MB) is an iron- and oxygen-binding protein found in the cardiac and skeletal muscle tissue of vertebrates in general and in almost all mammals. Myoglobin is distantly related to hemoglobin. Compared to hemoglobin, myoglob ...
,
hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythroc ...
, or certain
cytochrome Cytochromes are redox-active proteins containing a heme, with a central Fe atom at its core, as a cofactor. They are involved in electron transport chain and redox catalysis. They are classified according to the type of heme and its mode of ...
s is called
heme Heme, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver. In biochemical terms, heme is a coordination complex "consis ...
.
Metal complex A coordination complex consists of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of bound molecules or ions, that are in turn known as ''ligands'' or complexing agents. Many ...
es derived from porphyrins, often called metalloporphyins, occur naturally. One of the best-known families of porphyrin complexes is
heme Heme, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver. In biochemical terms, heme is a coordination complex "consis ...
, the pigment in red
blood cell A blood cell, also called a hematopoietic cell, hemocyte, or hematocyte, is a cell produced through hematopoiesis and found mainly in the blood. Major types of blood cells include red blood cells (erythrocytes), white blood cells (leukocytes) ...
s, a cofactor of the protein
hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythroc ...
. Porphin is the simplest porphyrin, a rare compound of theoretical interest. File:PPIXtransH.png, Derivatives of protoporphyrin IX are common in nature, the precursor to
heme Heme, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver. In biochemical terms, heme is a coordination complex "consis ...
s. 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 Heme, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver. In biochemical terms, heme is a coordination complex "consis ...
, a complex of a protoporphyrin IX.


Ancient porphyrins

A geoporphyrin, also known as a petroporphyrin, is a porphyrin of geologic origin. They can occur in
crude oil Petroleum, also known as crude oil, or simply oil, is a naturally occurring yellowish-black liquid mixture of mainly hydrocarbons, and is found in geological formations. The name ''petroleum'' covers both naturally occurring unprocessed crude ...
,
oil shale Oil shale is an organic-rich fine-grained sedimentary rock containing kerogen (a solid mixture of organic chemical compounds) from which liquid hydrocarbons can be produced. In addition to kerogen, general composition of oil shales constitut ...
, coal, or sedimentary rocks. Abelsonite is possibly the only geoporphyrin mineral, as it is rare for porphyrins to occur in isolation and form crystals. The field of organic geochemistry 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.


Biosynthesis

In non-photosynthetic
eukaryotes Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacter ...
such as animals, insects, fungi, and
protozoa Protozoa (singular: protozoan or protozoon; alternative plural: protozoans) are a group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic tissues and debris. Histo ...
, as well as the α-proteobacteria group of bacteria, the
committed step In enzymology, the committed step (also known as the ''first'' committed step) is an effectively irreversible enzymatic reaction that occurs at a branch point during the biosynthesis of some molecules. As the name implies, after this step, the mol ...
for porphyrin
biosynthesis Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecul ...
is the formation of δ-aminolevulinic acid (δ-ALA, 5-ALA or dALA) by the reaction of the
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid ( carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinog ...
with
succinyl-CoA Succinyl-coenzyme A, abbreviated as succinyl-CoA () or SucCoA, is a thioester of succinic acid and coenzyme A. Sources It is an important intermediate in the citric acid cycle, where it is synthesized from α-ketoglutarate by α-ketoglutarate d ...
from the
citric acid cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and prot ...
. In
plants Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae exclude ...
,
algae Algae (; singular alga ) is an informal term for a large and diverse group of photosynthetic eukaryotic organisms. It is a polyphyletic grouping that includes species from multiple distinct clades. Included organisms range from unicellular micr ...
,
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...
(except for the α-proteobacteria group) and
archaea Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaeba ...
, it is produced from
glutamic acid Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synt ...
via glutamyl-tRNA and
glutamate-1-semialdehyde Glutamate-1-semialdehyde is a molecule formed from by the reduction of tRNA bound glutamate, catalyzed by glutamyl-tRNA reductase. It is isomerized by glutamate-1-semialdehyde 2,1-aminomutase to give aminolevulinic acid in the biosynthesis of por ...
. The enzymes involved in this pathway are glutamyl-tRNA synthetase,
glutamyl-tRNA reductase A glutamyl-tRNA reductase () is an enzyme that catalyzes the chemical reaction :L-glutamate 1-semialdehyde + NADP+ + tRNAGlu \rightleftharpoons L-glutamyl-tRNAGlu + NADPH + H+ The 3 substrates of this enzyme are L-glutamate 1-semialdehyde, NAD ...
, and
glutamate-1-semialdehyde 2,1-aminomutase In enzymology, a glutamate-1-semialdehyde 2,1-aminomutase () is an enzyme that catalyzes the chemical reaction :L-glutamate 1-semialdehyde \rightleftharpoons 5-aminolevulinate Hence, this enzyme has one substrate, L-glutamate-1-semialdehyde, an ...
. This pathway is known as the C5 or Beale pathway. Two molecules of dALA are then combined by
porphobilinogen synthase Aminolevulinic acid dehydratase (porphobilinogen synthase, or ALA dehydratase, or aminolevulinate dehydratase) is an enzyme () that in humans is encoded by the ''ALAD'' gene. Porphobilinogen synthase (or ALA dehydratase, or aminolevulinate de ...
to give porphobilinogen (PBG), which contains a pyrrole ring. Four PBGs are then combined through deamination into
hydroxymethyl bilane Hydroxymethylbilane, also known as preuroporphyrinogen, is an organic compound that occurs in living organisms during the synthesis of porphyrins, a group of critical substances that include haemoglobin, myoglobin, and chlorophyll. The name is ofte ...
(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 Online Mendelian Inheritance in Man (OMIM) is a continuously updated catalog of human genes and genetic disorders and traits, with a particular focus on the gene-phenotype relationship. , approximately 9,000 of the over 25,000 entries in OMIM ...
database. The
porphyria Porphyria is a group of liver disorders in which substances called porphyrins build up in the body, negatively affecting the skin or nervous system. The types that affect the nervous system are also known as acute porphyria, as symptoms are ...
associated with the deficiency of each enzyme is also shown:


Laboratory synthesis

A common synthesis for porphyrins is the Rothemund reaction, first reported in 1936, which is also the basis for more recent methods described by Adler and Longo. The general scheme is a
condensation Condensation is the change of the state of matter from the gas phase into the liquid phase, and is the reverse of vaporization. The word most often refers to the water cycle. It can also be defined as the change in the state of water vapo ...
and
oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or ...
process starting with pyrrole and an
aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl gro ...
. :


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. This technique has been applied in
macular degeneration Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), is a medical condition which may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Over time, however, so ...
using verteporfin. 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. 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.


Toxicology

Heme biosynthesis is used as
biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, p ...
in environmental toxicology studies. While excess production of porphyrins indicate
organochlorine An organochloride, organochlorine compound, chlorocarbon, or chlorinated hydrocarbon is an organic compound containing at least one covalently bonded atom of chlorine. The chloroalkane class (alkanes with one or more hydrogens substituted by chlo ...
exposure,
lead Lead is a chemical element with the symbol Pb (from the Latin ) and atomic number 82. It is a heavy metal that is denser than most common materials. Lead is soft and malleable, and also has a relatively low melting point. When freshly cut, ...
inhibits
ALA dehydratase Aminolevulinic acid dehydratase (porphobilinogen synthase, or ALA dehydratase, or aminolevulinate dehydratase) is an enzyme () that in humans is encoded by the ''ALAD'' gene. Porphobilinogen synthase (or ALA dehydratase, or aminolevulinate de ...
enzyme.


Biological applications

Porphyrins have been investigated as possible anti-inflammatory agents and evaluated on their anti-cancer and anti-oxidant activity. Several porphyrin-peptide conjugates were found to have antiviral activity against HIV ''in vitro''.


Potential applications


Biomimetic catalysis

Although not commercialized, metalloporphyrin complexes are widely studied as catalysts for the oxidation of organic compounds. Particularly popular for such laboratory research are complexes of ''meso''- tetraphenylporphyrin and octaethylporphyrin. Complexes with Mn, Fe, and Co catalyze a variety of reactions of potential interest in
organic synthesis Organic synthesis is a special branch of chemical synthesis and is concerned with the intentional construction of organic compounds. Organic molecules are often more complex than inorganic compounds, and their synthesis has developed into one o ...
. Some complexes emulate the action of various
heme Heme, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver. In biochemical terms, heme is a coordination complex "consis ...
enzymes such as
cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...
, lignin peroxidase. Metalloporphyrins are also studied as catalysts for water splitting, with the purpose of generating molecular hydrogen and oxygen for fuel cells.


Molecular electronics and sensors

Porphyrin-based compounds are of interest as possible components of
molecular electronics Molecular electronics is the study and application of molecular building blocks for the fabrication of electronic components. It is an interdisciplinary area that spans physics, chemistry, and materials science. The unifying feature is use of mo ...
and photonics. Synthetic porphyrin dyes have been incorporated in prototype dye-sensitized solar cells. Metalloporphyrins have been investigated as sensors. Phthalocyanines, which are structurally related to porphyrins, are used in commerce as dyes and catalysts, but porphyrins are not.


Supramolecular chemistry

Porphyrins are often used to construct structures in
supramolecular chemistry Supramolecular chemistry refers to the branch of chemistry concerning chemical systems composed of a discrete number of molecules. The strength of the forces responsible for spatial organization of the system range from weak intermolecular forces ...
. 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. A guest-free base porphyrin is bound to the center by coordination with its four-pyridine substituents.


Theoretical interest in aromaticity

Porphyrinoid macrocycles can show variable aromaticity. An Hückel aromatic porphyrin is porphycene. antiaromatic, Mobius aromatic, and non aromatic porphyrinoid macrocycles are known.


See also

* A porphyrin-related disease:
porphyria Porphyria is a group of liver disorders in which substances called porphyrins build up in the body, negatively affecting the skin or nervous system. The types that affect the nervous system are also known as acute porphyria, as symptoms are ...
* Porphyrin coordinated to iron:
heme Heme, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver. In biochemical terms, heme is a coordination complex "consis ...
* A heme-containing group of enzymes:
Cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...
* Porphyrin coordinated to magnesium:
chlorophyll Chlorophyll (also chlorophyl) is any of several related green pigments found in cyanobacteria and in the chloroplasts of algae and plants. Its name is derived from the Greek words , ("pale green") and , ("leaf"). Chlorophyll allow plants to ...
* 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


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


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 In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Is ...
was reported by Emanual Vogel and coworkers in 1986. This isomer 8orphyrin-(2.0.2.0) is named as porphycene, and the central N4 Cavity forms a
rectangle In Euclidean plane geometry, a rectangle is a quadrilateral with four right angles. It can also be defined as: an equiangular quadrilateral, since equiangular means that all of its angles are equal (360°/4 = 90°); or a parallelogram contain ...
shape as shown in figure. Porphycenes showed interesting photophysical behavior and found versatile compound towards the photodynamic therapy. This inspired Vogel and Sessler to took up the challenge of preparing 8orphyrin-(2.1.0.1) and named it as Corrphycene or Porphycerin. The third porphyrin that is 8orphyrin-(2.1.1.0), was reported by Callot and Vogel-Sessler. Vogel and coworkers reported successful isolation of 8orphyrin-(3.0.1.0) or Isoporphycene. The Japanese scientist Furuta and Polish scientist Latos-Grażyński almost simultaneously reported the N-Confused porphyrins. The inversion of one of the pyrrolic subunits in the macrocyclic ring resulted to face one of the nitrogen atom outside of the core of the macrocycle.


References


External links


Journal of Porphyrins and Phthalocyanines



Porphynet – an informative site about porphyrins and related structures
{{Authority control Biomolecules Metabolism Photosynthetic pigments Chelating agents