Bioorganometallic chemistry

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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 (and can be viewed as exogenous biometal uses for molecular biology in such context; i.e. "inorganic" mediums for "organic" uses and processes). 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.[1][2]

Naturally occurring bioorganometallic species[edit]

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.[3] The Fe-only hydrogenases have a Fe2(μ-SR)2(μ-CO)(CO)2(CN)2 active site connected to a 4Fe4S 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).[4] 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[edit]

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[edit]

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; Titanocene Y {bis-[(p-methoxybenzyl)-cyclopentadienyl] titanium(IV) dichloride} is a current anticancer drug candidate. Arene- and cyclopentadienyl complexes are kinetically inert platforms for the design of new radiopharmaceuticals.

Furthermore, there have been made studies utilizing exogenous semi-synthetic ligands; specifically to the dopamine transporter, observing increased resultant efficacy in regard to reward facilitating behavior (Incentive salience) and habituation, namely with the phenyltropane compound [η6-(2β-carbomethoxy-3β-phenyl)tropane]tricarbonylchromium.

Bioorganometallics and toxicology[edit]

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.


  1. ^ Astrid Sigel, Helmut Sigel and Roland K.O. Sigel, ed. (2009). Metal-carbon bonds in enzymes and cofactors. Metal Ions in Life Sciences. 6. Royal Society of Chemistry. ISBN 978-1-84755-915-9. 
  2. ^ Synthetic Models for Bioorganometallic Reaction Centers, G. Jaouen; Wiley-VCH: Weinheim, 2005.
  3. ^ Cammack, R.; Frey, M. and Robson, R., Hydrogen as a Fuel: Learning from Nature, Taylor & Francis: London, 2001.
  4. ^ Volbeda, A. and Fontecilla-Camps, J. C., "The Active Site and Catalytic Mechanism of NiFe Hydrogenases", Dalton Transactions, 2003, 4030-4038.