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Porphyrin
One of a class of cyclic compounds in which the parent macrocycle consists of four pyrrole-type units
linked together by single carbon bridges. Several porphyrins with selected peripheral substitution and
metal coordination carry out vital biochemical processes in living organisms. Chlorins, bacteriochlorins,
and corrins are related tetrapyrrolic macrocycles that
are also observed in biologically important compounds (Fig. 1).
Nomenclature. The complexity of porphyrin nomenclature parallels the complex structures of the naturally occurring derivatives. Hans Fischer (who won
a Nobel prize for his studies on porphyrins) used a
simple numbering system for the porphyrin nucleus
[structure (I)] and a set of common names to identify
the different porphyrins and their isomers. A system
atic naming based on the 1-24 numbering system for
the porphyrin nucleus (II) was later developed by the
International Union of Pure and Applied Chemistry
(IUPAC) and the International Union of Biochemistry
(IUB), and this system has gained general acceptance.
The need for common names (see table) is clear after
examination of the systematic names; for example,
protoporphyrin IX has the systematic name 2,7,12,18tetramethyl-3,8-divinyl-13,17-dipropanoic acid.
Properties. The unique way in which some molecules can delocalize their own electrons make them
ally four additional bands in the 500-700-nm range.
In acidic solution, the inner =N- groups are proton ated, giving rise to the dication. This increases the
symmetry of the molecule and simplifies the optical
spectrum. SEE SPECTROPHOTOMETRIC ANALYSIS.
In addition to their biochemical roles, porphyrins,
metalloporphyrins, and their metabolic products the
bile pigments biliverdin and bilirubin (Fig. 3), are
used as pigments in nature. Indeed, many of the rich
colorations in birds' eggs are derived from porphyrin.
Phthalocyanins (HI), which are closely related to por-
especially stable. Such molecules (for example, benzene) are said to be aromatic. The aromatic character
(hence stability) of porphyrins has been confirmed by
measurements of their heats of combustion. In addition, x-ray crystallographic studies have established
planarity of the porphyrin macrocycle; this is a basic
requirement for aromatic character. SEE AROMATIC;
DELOCALIZATION; X-RAY CRYSTALLOGRAPHY.
Metal-free porphyrins are usually red-orange in solution. They exhibit characteristic optical spectra
(Fig. 2), with a very strong absorption band around
400 nanometers (known as the Soret band) and usu-
phyrins, are synthetic pigments. Like the porphyrins
they are both colorful and stable and are used indus
trially to color bluejeans and automobiles. SEE DYE.
MetallOporphyrins. Most metals and metalloid
have been inserted into the central hole of the por
phyrin macrocycle. The resulting metalloporphyrins
are usually very stable and can bind a variety of small
molecules (known as ligands) to the central metal
atom. Metalloporphyrins also exhibit a strong Soret
band, but have a simplified spectrum in the visible
region of their absorption spectrum due to increased
symmetry. In addition to the iron complexes (heme)
and magnesium complexes (chlorophyll and bacteriochlorophyll), other metalloporphyrins occur in nature. In particular, nickel and vanadium complexes
occur in oil, oil shales, and other geological deposits.
During the refining process involved in the conversion
of oil to gasoline, these very stable metalloporphyrins
pose many problems. SEE COORDINATION COMPLEXES.
Heme (Fig. 4), the iron complex of protoporphyrin
IX, is the prosthetic group of a number of major proteins and enzymes that carry out diverse biological
functions. These include binding, transport, and storage of oxygen (hemoglobin and myoglobin), electrontransfer processes (cytochromes), activation and
transfer of oxygen to substrates (cytochromes P-450),
and managing and using hydrogen peroxide (peroxidases and catalases). SEE CYTOCHROME;
ELECTRON-TRANSFER REACTION; ENZYME;
HEMOGLOBIN; IRON METABO-LISM; PROTEIN.
Chlorophylls and bacteriochlorophylls are magnesium complexes of porphyrin derivatives known as
chlorins and bacteriochlorins, respectively. They are
the pigments responsible for photosynthesis. Several
chlorophylls have been identified, the most common
being chlorophyll a (IV), which is found in all oxygen-evolving photosynthetic plants. Bacteriochlorophyll a (V) is found in many photosynthetic bacteria.
SEE CHLOROPHYLL; FLUORESCENCE COMPOUNDS
(PLANT);PHOTOSYNTHESIS .
Coenzyme B12 is the biologically active form of vitamin B12 (VI). The parent macrocycle, referred to as
corrin, is a highly reduced tetrapyrrole with one less
bridging carbon atom than the porphyrin. The B12
coenzyme and related corrinoids represent the most
complex nonpolymeric structures found in nature. In
addition, with a unique cobalt-carbon bond, they arc
the only known naturally occurring organometallic
complexes. Although many enzymatic reactions depend on coenzyme B12, its mechanism of action is not
yet fully understood. SEE COENZYME; VITAMIN B12.
Biosynthesis. Porphyrins and their related macrocycles found in nature are derived by the same biosynthetic pathway (Fig. 3). Glycine and succinic acid
are condensed to yield 8-aminolevulinic acid, which
is dimerized to the pyrrole porphobilinogen. Four
units of porphobilinogen are coupled to give uroporphyrinogen III (the Roman numerals here refer to the
order of the peripheral substituents). Uroporphyrinogen III is the cornerstone from which all other naturally occurring tetrapyrrolic macrocycles are made,
including heme, chlorophyll, bacteriochlorophyll, and
vitamin B|2. Each of the biosynthetic steps shown in
the reaction scheme in Fig. 3 is under enzymatic control. A number of genetic diseases known in humans,
the porphyrias, result from misfunctioning of the
heme biosynthetic pathway. These genetic disorders
can result in both neurological and dermatological
diseases.
In nature, porphyrins are synthesized by the tetramerization of a single pyrrolic unit (porphobilinogen;
Fig. 3). Chemists have developed similar synthetic
routes [reactions (l)-(3)]. Thus, the self-condensation
of 2-hydroxymethylpyrrole (VII) gives porphin (VIII)
[the parent structure in this class of compounds].
Similarly, coupling of 5-aminomethyl-3,4-diethylpyr-
role-2-carboxylic acid (IX) gives octaethylporphin
(X), while the condensation of pyrrole (XI) and benzaldehyde (XII) readily gives meso-tetraphenylporphyrin (XIII). Many additional synthetic routes to
porphyrins have been developed. SEE BIOSYNTHESIS.
Applications. Porphyrins and metalloporphyrins
exhibit many potentially important medicinal and industrial properties. Metalloporphyrins are being examined as potential catalysts for a variety of processes, including catalytic oxidations. They are also
being examined as possible blood substitutes and as
electrocatalysts for fuel cells and for the electrochemical generation of hydrogen peroxide. SEE CATALYSIS.
The unique optical properties of porphyrins make
them likely candidates for photovoltaic devices and in
photocopying and other optical devices. A major area
where porphyrins are showing significant potential is
in the treatment of a wide range of diseases, including
cancer, using photodynamic therapy (PDT). Because
of their unique optical and physical properties, many
porphyrins have the capacity to produce singlet oxygen when they are illuminated by visible light. If the
porphyrin could be made to accumulate in a tumor,
then bathing the tumor in red light might result in its
destruction. Photodynamic therapy using a porphyrinbased drug is in clinical trials and may eventually
prove a powerful tool in the treatment of cancer and
other diseases.
Photochemical techniques have been developed for
use in neonatal clinics. Many infants are jaundiced
and yellow at birth because of their inability to metabolize bilirubin (Fig. 3), a metabolite of heme. Bilirubin can be neurotoxic. However, by merely placing
the jaundiced child under a fluorescent lamp, the
buildup of bilirubin is diminished to safe levels until
the infant's own bilirubin metabolism increases. SEE
BILIRUBIN; COORDINATION CHEMISTRY; PYRROLE.
T. Wijesekera; D. Dolphin
Bibliography. P. K. Bondy and L. E. Rosenberg
(eds.), Metabolic Control and Disease, 1980; D. Dolphin (ed.), The Porphyrins, vols. 1-7, 1978-1979;
IUPAC-IUB, Nomenclature of tetrapyrroles, Europ.
J. Biochem., 178:277-328, 1988.