Organometallic and Bioorganometallic Chemistry - Ferrocene and Metal Carbonyls

Organometallic chemistry deals with compounds containing metal-carbon bonds. Basic organometallics derived from the s- and p-block metals (containing solely σ-bonds) were understood earlier, while organometallic chemistry of the d- and f-block has developed much more recently. These compounds are characterized by three types of M-C bonds (σ, π and δ)and their structures are impossible to deduce by chemical means alone; fundamental advances had to await the development of X-ray diffraction, as well as IR- and NMR-spectroscopy. On the other hand, elucidation of the structure of e. g. vitamin B12 and ferrocene (discovered in 1951) contributed to progress in these instrumental analytical methods, influencing further phenomenal success of transition-metal organometallic chemistry in the second half of the twentieth century. The most thoroughly explored fields of application of organometallics were in the area of catalysis, asymmetric synthesis, olefin metathesis, as well as organic synthesis and access to new materials and polymers.The most usual ligands bound to d- and f-metals are carbon monoxide, phosphines, alkyls, carbenes and arenes, and in this review the bonding patterns in the metal carbonyls and ferrocene are elaborated. The common characteristics of these two classes are two-component bonds. The CO-M bonds include (i) donation from ligand HOMO to vacant M d-orbitals (σ-bond), and (ii) back-donation from the filled M d-orbitals in the ligand LUMO (π-bond). Similar (but much more complicated) ferrocene contains delocalized bonds consisting of electron donation from Cp to Fe (σ-bonds- and π-bonding) and δ-back-bonding from metal to Cp. In such a way ferrocene, i. e. (η5-Cp)2Fe contains 18 bonding electrons giving to this compound "superaromatic" properties in the sense of stability and electrophilic substitution. In contrast to benzenoid aromatic compounds reactions in two Cp-rings can occur giving homo- and heteroannularly mono-, two-… per-substituted products. Owing to the low barrier to internal rotation around Cp-Fe-Cp axis (ω torsion angle) ferrocene is characterized by D5d-symmetrical staggered and D5h-symetrical eclipsed forms. In the appropriately substituted ferrocenes, deviation from Cp coplanarity (tilt angle Θ) may occur as well; e. g. ferrocenophanes are derivatives in which homo- or heteroatomic bridges spanned two Cp rings, causing appreciable deformations of ferrocene molecule (ω=0–26°; Θ=9–24°). A characteristic development of the science in the new age has been the gradual merging of what were once separate research disciplines. In such a way, on the border between classical organic and inorganic chemistry (long ago) organometallic chemistry was established and in the last decades "hybridization" of biology (biochemistry) and organometallic chemistry has resulted in the appearance of bioorganometallic chemistry. In short, this new discipline deals with conjugates of organometallics with biomolecules (DNA, PNA, carbohydrates, steroids, amino acids, peptides...). The principal fields of research activity in bioorganometallic chemistry are therapy, bioanalysis (sensors), molecular recognition in aqueous medium, enzymes (proteins, peptides), toxicology and environment.This article reviews only a few (interesting) examples out of the immense number of bioorganometallics (classes). Many bioorganometallic drugs showed improved bioactivity in comparison with their classical anticancer and antimalarial analogues (e. g. tamoxifene → hydroxyferrocifene; chloroquine → ferroquine). Organometallic bioprobes are the molecules incorporating organometallic responding components (e. g. metal carbonyls). In the appropriately designed devices, these "molecular sensors" read out the information that is available from the molecular recognition events by FT-IR spectroscopy. Electrochemically active bioorganometallics (e. g. probes containing ferrocene) are used in biosensors for detection of DNA, glucose in blood, etc. The procedure to use metal atoms in organometallics as labelling agents for antigens (A) in immunoassays (IA) is called metalloimmunoassay (MIA, Cais, 1977). Carbonyl metalloimmunoassay (CMIA) is a heterogeneous competitive-type MIA using M-CO complexes as tracers, and FT-IR spectroscopy for quantification. This procedure allowed the simultaneous multiple IA reaching the fentomole concentration (Jaouen, 2000). From the variety of bioorganometallics synthesis and properties of the simple ferrocene-amino acids/peptides conjugates and ferrocene labelled carbohydrates, as well as the structure and function determination of B12 vitamin are described in this review