Selective, Cytotoxic Organoruthenium(II) Full‐Sandwich Complexes: A Structural, Computational and In Vitro Biological Study

A structurally diverse range of lipophilic, cationic η⁶‐arene η⁵‐cyclopentadienyl (η⁵‐Cp*) full‐sandwich complexes of ruthenium(II) have been prepared and structurally characterized by Fourier‐transform IR and NMR spectroscopy, electrospray mass spectrometry, and elemental microanalyses. Computational experiments incorporating the Hartree–Fock theory and the second‐order Møller–Plesset perturbation theory predict each complex to possess a uniform δ+ electrostatic potential, with the cationic charge of the [RuCp*]⁺ moiety completely delocalizing throughout the molecular structure of each metallocene. In vitro cytotoxicity studies demonstrate these delocalized lipophilic cations to be potent growth inhibitors of eleven unique tumorigenic cell lines, while exhibiting significantly lower levels of toxicity towards both a normal human fibroblast and a mouse macrophage cell line. Single‐crystal X‐ray structural determinations are additionally reported for five complexes, [Ru(η⁶‐C₆H₅(CH₂)₂CH₃)(η⁵‐C₅(CH₃)₅)]BPh₄, [Ru(η⁶‐C₆H₅CO₂CH₂CH₃)(η⁵‐C₅(CH₃)₅)]BF₄, [Ru(η⁶‐C₁₀H₈)(η⁵‐C₅(CH₃)₅)]BPh₄, [Ru(η⁶‐C₁₄H₁₀)(η⁵‐C₅(CH₃)₅)]BPh₄, and [Ru(η⁶‐C₁₆H₁₀)(η⁵‐C₅(CH₃)₅)]BPh₄.