Diiron(I) Bis(cyclopentadienyl) Complexes with Bridging Iminium Ligands: From Foundational Organometallic Chemistry to Unique Reactivity and Biological Potential

ConspectusDimetallic complexes offer a remarkable platform to probe metal-metal cooperativity, enabling ligand reactivity patterns that are inaccessible to mononuclear systems. Starting from [Fe₂Cp₂(CO)₄] (Fp₂, Cp = η⁵-C₅H₅), diiron μ-aminocarbyne (iminium) complexes are available through a straightforward multigram-scale procedure. Carbonyl removal is key to enabling selective modification of the ligand set and promoting the formation of uncommon hydrocarbyl ligands involving the carbyne center. In this context, the insertion of terminal alkynes into iron-carbynes bond affords a wide diversity of vinyliminium complexes, characterized by a highly versatile and modular reactivity with reasonably broad reaction scopes. Specifically, three representative transformations are discussed in this Account: 1) Cyanide addition, leading to a cyano-aminoallylidene ligand, in which an intramolecular amine-CO interaction dictates the stereochemical outcome and facilitates subsequent thermal CO dissociation, thereby enabling further reaction pathways. 2) Incorporation of a selenium atom through vinyliminium deprotonation, yielding intrinsically stable complexes bearing an almost pure selenolate function. This moiety displays marked nucleophilic reactivity, including facile dimerization to a Fe₄ framework via selenide-to-diselenide oxidation, as well as the construction of a selenophene-decorated Fischer alkylidene ligand. Mild hydrolytic cleavage breaks the alkylidene bridge, providing access to a new family of highly functionalized selenophenes. 3) Vinyliminium deprotonation, representing a key entry point to the first family of ferrabenzenes. A multicomponent assembly involving one carbonyl ligand and ethyl diazoacetate generates a six-membered metallacycle, which is ultimately converted into substituted ferrabenzenes through O-alkylation.Beyond their organometallic reactivity, cationic aminocarbyne and vinyliminium complexes display a combination of properties that are highly attractive for medicinal applications, including straightforward synthesis, air and aqueous stability, broad structural tunability, and amphiphilicity. These features prompted their evaluation as anticancer agents. Their cytotoxicity relies on a molecular "time bomb" behavior, as extensive fragmentation of the diiron scaffold occurs intracellularly, releasing reactive iron(I) species and carbon monoxide. The resulting fragments primarily induce mitochondrial dysfunction, leading to disruption of cellular redox homeostasis. Importantly, both cytotoxicity and mechanism of action can be regulated by the choice of substituents and ligands, and appreciable cancer cell selectivity is generally achieved. Notably, selected complexes confirmed their promise in 3D cellular models and, in one case, <i>in vivo</i>, warranting further development of these diiron-based anticancer agents.Overall, this Account traces a long-term research journey centered on diiron bis(cyclopentadienyl) complexes. The narrative begins in a historical context where organometallic chemistry was largely confined to inert-atmosphere manipulation and biological or aqueous applications were scarcely envisioned. It then progresses through the discovery of novel organometallic reactivity patterns and motifs enabled by metal-metal cooperativity, with emphasis on the most recent advances, and culminates in the transition toward biological applications. Collectively, these studies illustrate how fundamental organometallic chemistry can naturally evolve into the concepts and principles of modern bioorganometallic chemistry.