Bioorganometallic chemistry

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 enzymes and sensor proteins. 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 B12 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.

Hydrogenases 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.

Sensor proteins
Some [NiFe]-containing proteins are known to sense H2 and thus regulate transcription.

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. Cyclopropenes 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 cisplatin in chemotherapy. (C5H5)2TiCl2 displays anti-cancer activity. Arene- and cyclopentadienyl complexes are kinetically inert platforms for the design or 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 tricarbonyl. Methylmercury is a particularly infamous case, this cation is produced by the action of vitamin B12-related enzymes on mercury.