The multidisciplinary field of bioorganometallic chemistry

Contemporary scientific inquiry is increasing focused on problems that reside at the interfaces between and among traditional disciplines. So is the case of the ever-burgeoning field known as bioorganometallic chemistry. In its most inclusive sense, this field encompasses organometallic chemistry, i.e. species with direct metal–carbon bond(s), in a biological context. Practitioners derive from the traditional fields of biochemistry, inorganic chemistry, organic chemistry, biophysics, structural biology, and microbiology. One measure of the growth of this field is the increase in citations that contain the term “bioorganometallic.” Since its introduction in the literature in 1975, the term has been used with increasing frequency with ca. fifty papers published in 2008. It is clear that the number of papers that describe bioorganometallic chemistry outpace those that specifically used the term.

The earliest and most thoroughly documented examples of organometallics in biology are the vitamin B₁₂ derivatives adenosyl-cobalamin and methyl-cobalamin. These cofactors exquisitely promote one- and two-electron reactions via homolytic and heterolytic rupture of Co–C bonds, respectively. Spurred by advances in structural biology, i.e. the availability of high resolution protein X-ray structures, more recent emphasis has been placed on understanding the structure and function of nickel-containing enzymes that shuttle one-carbon substrates about in the anaerobic world and the hydrogenases that utilize the extraordinary Fe(CO)_x(CN)_y cofactor in promoting reversible oxidation of H₂. In these pursuits there is significant intellectual overlap and synergy between classical organometallic catalysis and metallobiochemistry.

Complementary approaches take advantage of well-developed synthetic methodologies to install organometallic fragments into bioactive molecules. The resulting bioconjugates are used to impart desirable physical attributes (e.g. enhanced ability to cross membranes and accumulate in tissue cell types), as biophysical probes, diagnostics or in the treatment of diseases. As but one example, the application of transition metal carbonyl fragments as tags for immunoassays leads to picomolar detection sensitivity.

The activity of organometallics in the environment remains an area of significant interest and impact. While many main group organometallics are susceptible to hydrolysis, organomercurials are not. Consequently, bacteria have developed a complex operon to sense, transport and degrade these pernicious byproducts of industrial activity.

There is clear synergy among these aforementioned areas. In these settings the organometallic moieties are robust entities that offer varied utility including as ligands in enzyme intermediates and their synthetic models, labile groups for delivery of CO, structural elements for bioconjugates, spectroscopic probes and in antifugal agents. To further enhance and highlight this synergy, this issue of Dalton Transactions brings together a collection of original articles from leaders in the field to heighten the visibility of bioorganometallic chemistry and to spur excitement and opportunity among the next generation of scholars. Enjoy!

Charles G. Riordan

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