Bioorganometallic chemistry
Encyclopedia
Bioorganometallic chemistry is the study of biologically active molecules that contain carbon directly bonded to metals or metalloids. This area straddles the fields of organometallic chemistry
, biochemistry
, and medicine
. It is subset of bioinorganic chemistry
. Naturally occurring bioorganometallics include enzyme
s and sensor protein
s. Also within this realm is the development of new drugs and imaging agents as well as the principles relevant to the toxicology or organometallic compounds.
is the preeminent bioorganometallic species. B12 is shorthand for a collection of related enzymes which effect numerous reactions involving the making and breaking of C-C and C-H bonds.
Several bioorganometallic enzymes carry out reactions involving carbon monoxide
. Carbon monoxide dehydrogenase (CODH) catalyzes the water gas shift reaction
which provides CO for the biosynthesis of acetylcoenzyme A
. The latter step is effected by the Ni-Fe enzyme acetylCoA synthase
. ACS”. CODH and ACS often occur together in a tetrameric complex, the CO being transported via a tunnel and the methyl group being provided by methyl cobalamin.
Hydrogenase
s are bioorganometallic in the sense that their active sites feature Fe-CO functionalities, although the CO ligands are only spectators. The Fe-only hydrogenases have a Fe2(μ-SR)2(μ-CO)(CO)2(CN
)2 active site connected to a 4Fe4S cluster
cluster via a bridging thiolate. The active site of the [NiFe]-hydrogenases are described as (NC)2(OC)Fe(μ-SR)2Ni(SR)2 (where SR is cysteinyl
). The “FeS-free” hydrogenases have an undetermined active site containing an Fe(CO)2 center.
Methanogenesis
, the biosynthesis of methane, entails as its final step, the scission of a nickel
-methyl bond in cofactor F430.
Copper
-containing proteins are known to sense ethylene, which is known to be a hormone relevant to the ripening of fruit. This example illustrates the essential role of organometallic chemistry in nature, as few molecules outside of low-valent transition metal complexes reversibly bind alkenes. Cyclopropene
s inhibit ripening by binding to the copper(I) center.
Carbon monoxide occurs naturally and is a transcription factor via its complex with a sensor protein based on ferrous porphyrins.
in chemotherapy. (C5H5)2TiCl2
displays anti-cancer activity. Arene
- and cyclopentadienyl
complexes are kinetically inert platforms for the design of new radiopharmaceuticals.
. Methylmercury
is a particularly infamous case, this cation is produced by the action of vitamin B12-related enzymes on mercury.
Organometallic chemistry
Organometallic chemistry is the study of chemical compounds containing bonds between carbon and a metal. Since many compounds without such bonds are chemically similar, an alternative may be compounds containing metal-element bonds of a largely covalent character...
, biochemistry
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
, and medicine
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
. It is subset of bioinorganic chemistry
Bioinorganic chemistry
Bioinorganic chemistry is a field that examines the role of metals in biology. Bioinorganic chemistry includes the study of both natural phenomena such as the behavior of metalloproteins as well artificially introduced metals, including those that are non-essential, in medicine and toxicology...
. Naturally occurring bioorganometallics include enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s and sensor protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s. Also within this realm is the development of new drugs and imaging agents as well as the principles relevant to the toxicology or organometallic compounds.
Naturally occurring bioorganometallic species
Vitamin B12Vitamin B12
Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...
is the preeminent bioorganometallic species. B12 is shorthand for a collection of related enzymes which effect numerous reactions involving the making and breaking of C-C and C-H bonds.
Several bioorganometallic enzymes carry out reactions involving carbon monoxide
Carbon monoxide
Carbon monoxide , also called carbonous oxide, is a colorless, odorless, and tasteless gas that is slightly lighter than air. It is highly toxic to humans and animals in higher quantities, although it is also produced in normal animal metabolism in low quantities, and is thought to have some normal...
. Carbon monoxide dehydrogenase (CODH) catalyzes the water gas shift reaction
Water gas shift reaction
The water-gas shift reaction is a chemical reaction in which carbon monoxide reacts with water vapor to form carbon dioxide and hydrogen:The water-gas shift reaction is an important industrial reaction. It is often used in conjunction with steam reforming of methane or other hydrocarbons, which is...
which provides CO for the biosynthesis of acetylcoenzyme A
Coenzyme A
Coenzyme A is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All sequenced genomes encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it as a substrate...
. The latter step is effected by the Ni-Fe enzyme acetylCoA synthase
Synthase
In biochemistry, a synthase is an enzyme that catalyses a synthesis process.Following the EC number classification, they belong to the group of ligases, with lyases catalysing the reverse reaction....
. ACS”. CODH and ACS often occur together in a tetrameric complex, the CO being transported via a tunnel and the methyl group being provided by methyl cobalamin.
Hydrogenase
Hydrogenase
A hydrogenase is an enzyme that catalyses the reversible oxidation of molecular hydrogen . Hydrogenases play a vital role in anaerobic metabolism....
s are bioorganometallic in the sense that their active sites feature Fe-CO functionalities, although the CO ligands are only spectators. The Fe-only hydrogenases have a Fe2(μ-SR)2(μ-CO)(CO)2(CN
Cyanide
A cyanide is a chemical compound that contains the cyano group, -C≡N, which consists of a carbon atom triple-bonded to a nitrogen atom. Cyanides most commonly refer to salts of the anion CN−. Most cyanides are highly toxic....
)2 active site connected to a 4Fe4S cluster
Iron-sulfur protein
Iron-sulfur proteins are proteins characterized by the presence of iron-sulfur clusters containing sulfide-linked di-, tri-, and tetrairon centers in variable oxidation states...
cluster via a bridging thiolate. The active site of the [NiFe]-hydrogenases are described as (NC)2(OC)Fe(μ-SR)2Ni(SR)2 (where SR is cysteinyl
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
). The “FeS-free” hydrogenases have an undetermined active site containing an Fe(CO)2 center.
Methanogenesis
Methanogenesis
Methanogenesis or biomethanation is the formation of methane by microbes known as methanogens. Organisms capable of producing methane have been identified only from the domain Archaea, a group phylogenetically distinct from both eukaryotes and bacteria, although many live in close association with...
, the biosynthesis of methane, entails as its final step, the scission of a nickel
Nickel
Nickel is a chemical element with the chemical symbol Ni and atomic number 28. It is a silvery-white lustrous metal with a slight golden tinge. Nickel belongs to the transition metals and is hard and ductile...
-methyl bond in cofactor F430.
Sensor proteins
Some [NiFe]-containing proteins are known to sense H2 and thus regulate transcription.Copper
Copper
Copper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...
-containing proteins are known to sense ethylene, which is known to be a hormone relevant to the ripening of fruit. This example illustrates the essential role of organometallic chemistry in nature, as few molecules outside of low-valent transition metal complexes reversibly bind alkenes. Cyclopropene
Cyclopropene
Cyclopropene is an organic compound with the formula 34. It is the simplest isolable cycloalkene. It has a triangular structure. Because the ring is highly strained, cyclopropene is both difficult to prepare and interesting to study. Like cyclopropane, the carbon ring of cyclopropene is planar...
s inhibit ripening by binding to the copper(I) center.
Carbon monoxide occurs naturally and is a transcription factor via its complex with a sensor protein based on ferrous porphyrins.
Organometallics in medicine
Several organometallic compounds are under study as candidates for diverse therapies. Much work was instigated by the success of cisplatinCisplatin
Cisplatin, cisplatinum, or cis-diamminedichloroplatinum is a chemotherapy drug. It is used to treat various types of cancers, including sarcomas, some carcinomas , lymphomas, and germ cell tumors...
in chemotherapy. (C5H5)2TiCl2
Titanocene dichloride
Titanocene dichloride is the organotitanium compound with the formula 2TiCl2, commonly abbreviated as Cp2TiCl2. This metallocene is a common reagent in organometallic and organic synthesis. It exists as a bright red solid that slowly hydrolyzes in air...
displays anti-cancer activity. Arene
Arene
Arene or Arênê or Arène may refer to:*an aromatic hydrocarbon*Arene , a genus of marine snails in the family Areneidae*Arene , the wife of Aphareus and mother of Idas and Lynceus in Greek mythology...
- and cyclopentadienyl
Cyclopentadienyl
In organic chemistry, cyclopentadienyl is a cyclic group of atoms with the formula C5H5. Cyclopentadienyl are closely related to cyclopentadiene. Cyclopentadienyl have five carbon atoms bonded together in a pentagonal planar ring, all five of which are bonded to individual hydrogen atoms...
complexes are kinetically inert platforms for the design of new radiopharmaceuticals.
Bioorganometallics and toxicology
Within the realm of bioorganometallic chemistry is the study of the fates of synthetic organometallic compounds. Tetraethyllead has received considerable attention in this regard as has its successors such as methylcyclopentadienyl manganese tricarbonylMethylcyclopentadienyl manganese tricarbonyl
Methylcyclopentadienyl manganese tricarbonyl is an organomanganese compound with the formula Mn3. Marketed initially in 1958 as a supplement to the gasoline additive tetraethyl lead to increase the fuel's octane rating, MMT was later used in unleaded gasoline...
. Methylmercury
Methylmercury
Methylmercury is an organometallic cation with the formula . It is a bioaccumulative environmental toxicant.-Structure:...
is a particularly infamous case, this cation is produced by the action of vitamin B12-related enzymes on mercury.