Crown jewel of organometallic chemistry

structure of ferrocene, source: original article

Nowadays, ferrocene is one of the iconic compounds of organometallic chemistry, and its discovery was an important milestone in this field. Keally and Pauson immediately recognized the significance of their discovery, but they couldn’t correctly identify the structure of the newly prepared compound. Shortly after, the correct structure was proposed independently by scientists from Harvard University and Technical University Munich. The sandwich structure of ferrocene was revolutionary in the 1950s. Twenty years later, in 1973, they even won a Nobel Prize for their discovery. Ferrocene got its name after benzene to emphasize its aromatic nature. The importance of ferrocene lies in the huge variety of applications, of which we still have much more to explore even now.

One of the main fields of ferrocene applications is catalysis. Ferrocene compounds are used to make other reactions happen or to speed them up. If the ferrocene ligand (a part of a coordination compound bound to the central metal atom) is chiral, it is possible to use it in enantioselective catalysis and synthesize optically pure compounds. The optical purity is important for further applications of such compounds, as the isomers can display very different biological behavior. For example, one can be a very good drug while the other can be highly toxic. Some ferrocene derivatives are widely used in industrial catalysis, and the palette of reactions where they can be used keeps getting more diverse. Even more, diversity is ensured by ferrocene's ability of well-defined reversible oxidation. This can be used in redox catalysts whose behavior depends on the redox state of ferrocene.

Another field of use of ferrocene is pharmaceutical research. Although no ferrocene compound is approved for clinical use these days, ferrocene is part of many molecules in new drug development, mainly concerning cancer and malaria. In the beginning, the research was focused mainly on simple ferrocenium salts, which can contribute to cell death. Nowadays, the focus has shifted towards more complicated complex compounds where ferrocene is connected to another part, usually a complex compound of transition metal. These substances are able to combine different effects, such as effective targeting of these drugs or fluorescent labeling that can facilitate tracking of the molecule in the human body. This could enlighten some of their mechanisms of action, as those are currently very poorly understood and prevent potential ferrocene drugs from getting into clinical trials and practical use.

Low toxicity, reversible oxidation, and unique stability give ferrocene many more practical applications. Its derivatives are important for material chemistry. Just a few years after the discovery of ferrocene, in 1955, its effectiveness as a fuel additive was published. This continued to evolve, eventually fully replacing the toxic lead compounds and making so-called unleaded gasoline. Ferrocene compounds can also be found in optical and electronic materials and can also be used as iron sources in nanoparticle preparation.

The chemistry of ferrocene has seen a huge evolution which brought many practical applications. The research is still very much alive even after 70 years and is going faster than ever. Thanks to its unique properties, ferrocene has planted its roots in many fields of chemistry and still has much more to offer.

Štěpnička, P. Forever Young: The First Seventy Years of Ferrocene. Dalton Trans. 2022, 51, 8085–8102.

Magda Křelinová