The parent of porphyrins is
porphine, a rare chemical compound of exclusively theoretical interest. Substituted porphines are called porphyrins.[1] 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.[2][3] One result of the large
conjugated system 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 word πορφύρα (porphyra), meaning purple.[4]
Structure
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.[5] Additionally, the metal is often not centered in the N4 plane.[6] For free porphyrins, the two pyrrole protons are mutually trans and project out of the N4 plane.[7] These nonplanar distortions are associated with altered chemical and physical properties.
Chlorophyll-rings are more distinctly nonplanar, but they are more saturated than porphyrins.[8]
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 + [MLn2+ → M(porphyrinate)Ln−4 + 4 L + 2 H+, where M = metal ion and L = a ligand
Octaethylporphyrin (H2OEP) is a synthetic analogue of protoporphyrin IX. Unlike the natural porphyrin ligands, OEP2− is highly symmetrical.
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.
Simplified view of
heme, a complex of a protoporphyrin IX.
A geoporphyrin, also known as a petroporphyrin, is a porphyrin of geologic origin.[9] They can occur in
crude oil,
oil shale, coal, or sedimentary rocks.[9][10]Abelsonite is possibly the only geoporphyrin mineral, as it is rare for porphyrins to occur in isolation and form crystals.[11]
The field of
organic geochemistry had its origins in the isolation of porphyrins from petroleum.[citation needed] This finding helped establish the biological origins of petroleum. Petroleum is sometimes "fingerprinted" by analysis of trace amounts of nickel and
vanadyl porphyrins.[citation needed]
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:
A common synthesis for porphyrins is the
Rothemund reaction, first reported in 1936,[12][13] which is also the basis for more recent methods described by Adler and Longo.[14] The general scheme is a
condensation and
oxidation process starting with pyrrole and an
aldehyde.
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.[15] This technique has been applied in
macular degeneration using
verteporfin.[16]
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.[17] 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.[18]
Porphyrins have been investigated as possible anti-inflammatory agents[22] and evaluated on their anti-cancer and anti-oxidant activity.[23] Several porphyrin-peptide conjugates were found to have antiviral activity against HIV in vitro.[24]
Toxicology
Heme biosynthesis is used as
biomarker in environmental toxicology studies. While excess production of porphyrins indicate
organochlorine exposure,
lead inhibits
ALA dehydratase enzyme.[25]
A benzoporphyrin is a porphyrin with a benzene ring fused to one of the pyrrole units. e.g.
verteporfin is a benzoporphyrin derivative.[26]
Non-natural porphyrin isomers
The first synthetic porphyrin
isomer was reported by Emanual Vogel and coworkers in 1986.[27] 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.[28] Porphycenes showed interesting
photophysical behavior and found versatile compound towards the
photodynamic therapy.[29] This inspired Vogel and
Sessler to took up the challenge of preparing [18]porphyrin-(2.1.0.1) and named it as corrphycene or porphycerin.[30] The third porphyrin that is [18]porphyrin-(2.1.1.0), was reported by Callot and Vogel-Sessler. Vogel and coworkers reported successful isolation of [18]porphyrin-(3.0.1.0) or isoporphycene.[31] The Japanese scientist Furuta[32] and Polish scientist Latos-Grażyński[33] almost simultaneously reported the N-confused porphyrins. The inversion of one of the pyrrolic subunits in the macrocyclic ring resulted in one of the nitrogen atoms facing outwards from the core of the macrocycle.
^Ivanov AS, Boldyrev AI (August 2014). "Deciphering aromaticity in porphyrinoids via adaptive natural density partitioning". Organic & Biomolecular Chemistry. 12 (32): 6145–6150.
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^Lash TD (2011). "Origin of aromatic character in porphyrinoid systems". Journal of Porphyrins and Phthalocyanines. 15 (11n12): 1093–1115.
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^Harper D, Buglione DC.
"porphyria (n.)". The Online Etymology Dictionary. Retrieved 14 September 2014.
^Senge MO, MacGowan SA, O'Brien JM (December 2015). "Conformational control of cofactors in nature - the influence of protein-induced macrocycle distortion on the biological function of tetrapyrroles". Chemical Communications. 51 (96): 17031–17063.
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^Zhang B, Lash TD (September 2003). "Total synthesis of the porphyrin mineral abelsonite and related petroporphyrins with five-membered exocyclic rings". Tetrahedron Letters. 44 (39): 7253.
doi:
10.1016/j.tetlet.2003.08.007.
^Rothemund P (1935). "Formation of Porphyrins from Pyrrole and Aldehydes". J. Am. Chem. Soc. 57 (10): 2010–2011.
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10.1021/ja01313a510.
^Adler AD, Longo FR, Finarelli JD, Goldmacher J, Assour J, Korsakoff L (1967). "A simplified synthesis for meso-tetraphenylporphine". J. Org. Chem.32 (2): 476.
doi:
10.1021/jo01288a053.
^Giuntini F, Boyle R, Sibrian-Vazquez M, Vicente MG (2014). "Porphyrin conjugates for cancer therapy". In Kadish KM, Smith KM, Guilard R (eds.). Handbook of Porphyrin Science. Vol. 27. pp. 303–416.
^Vogel E, Köcher M (March 1986). "Porphycene—a Novel Porphin Isomer". Angewandte Chemie. 25 (3): 257.
doi:
10.1002/anie.198602571.
^Nagamaiah J, Dutta A, Pati NN, Sahoo S, Soman R, Panda PK (March 2022). "3,6,13,16-Tetrapropylporphycene: Rational Synthesis, Complexation, and Halogenation". The Journal of Organic Chemistry. 87 (5): 2721–2729.
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^Dougherty TJ (2001). "Basic principles of photodynamic therapy". Journal of Porphyrins and Phthalocyanines. 5 (2): 105.
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10.1002/jpp.328.
^Vogel E, Guilard R (November 1993). "New Porphycene Ligands: Octaethyl‐ and Etioporphycene (OEPc and EtioPc)—Tetra‐ and Pentacoordinated Zinc Complexes of OEPc". Angewandte Chemie International Edition. 32 (11): 1600.
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^Hiroyuki F (1994). ""N-Confused Porphyrin": A New Isomer of Tetraphenylporphyrin". J. Am. Chem. Soc. 116 (2): 767.
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10.1021/ja00081a047.
^Chmielewski PJ, Latos-Grażyński L, Rachlewicz K, Glowiak T (18 April 1994). "Tetra‐p‐tolylporphyrin with an Inverted Pyrrole Ring: A Novel Isomer of Porphyrin". Angewandte Chemie International Edition. 33 (7): 779.
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