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Highlights A new family of indole-containing arene ruthenium organometallic compounds are active against several bacterial species and drug resistant strains Bactericidal activity observed against various Gram negative, Gram positive and acid-fast bacteria, demonstrating broad-spectrum inhibitory activity Compound series exhibits low toxicity against human cells Shows considerable promise as next generation antibiotics

The synthesis, characterisation and evaluation of the in vitro cytotoxicity of four indole-based half-sandwich metal complexes towards two ovarian cancer cell lines (A2780 and A2780cisR) and one normal prostate cell line (PNT2) are presented herein. Although capable of inducing catalytic oxidation of NADH and able to reduce NAD+ with high turnover frequencies, in cells and in the presence of sodium formate, these complexes also strongly interact with biomolecules such as glutathione. This work highlights that efficient out-of-cells catalytic activity might lead to higher reactivity towards biomolecules, thus inhibiting the in-cells catalytic processes.

The precursor PPyrCl 2 (Pyr = 1-pyrenyl) has been used to prepare a number of novel 1-pyrenylphosphines. Treatment of PPyrCl 2 with methylmagnesium chloride has provided the phosphine PPyrMe2, with methanol/triethylamine, the phosphonite PPyr­(OMe)2 (1), with dimethylamine/triethylamine, the diaminophosphine PPyr­(NMe2)2 (2), and with lithium aluminum hydride, PPyrH2 (3). From this primary phosphine, phosphirane PPyr­(CH2CH2) (5) has been obtained. The phosphine PPyr2Ph (6) has been synthesized from 1-bromopyrene, while 1-bromo-2-(1-pyrenyl)­benzene has been used to prepare Ph-PyrPhos (7) and i-Pr-PyrPhos (8). The new phosphines have subsequently been used to obtain the corresponding [RuCl2(η6-arene)­(PPyrR2)] complexes C1 Cym –C3 Cym and C6 Cym –C8 Cym (arene = p-cymene; Cym) and C1 Mba –C3 Mba and C6 Mba –C8 Mba (arene = methyl benzoate; Mba), which have been fully characterized; the crystal structures of C1 Cym , C1 Mba , C2 Cym , C2 Mba , C6 Mba , and C7 Cym were determined by X-ray diffraction. Substitution of the methyl benzoate fragment of complexes C7 Mba and C8 Mba by the η6-coordinated pyrenyl group of the coordinated phosphine was achieved photochemically, giving the tethered complexes C7 Tet and C8 Tet . In these two complexes the phosphine acts as a κ1,η6-coordinated ligand, as evidenced by the X-ray structure of C8 Tet . The antineoplastic activities of the piano-stool Ru compounds revealed that they are highly phosphine dependent and two compounds, namely C1 Cym and C2 Cym , exhibit interesting biological properties.

The synthesis, characterisation, and evaluation of the in vitro cytotoxicity of five maleonitriledithiolate‐based ruthenium metal complexes bearing various phosphine ligands towards two ovarian cancer cell lines (A2780 and A2780cisR), one non‐small‐cell lung cancer cell line (H460) and one normal prostate cell line (PNT2) are presented herein. These 18‐electron complexes were designed with four water‐soluble phosphine ligands to increase the water‐solubility character of the corresponding electron‐deficient ruthenium complex which showed great in vitro promises, and triphenylphosphine for comparison. The complexes with triphenylphosphine‐3,3′,3′′‐trisulfonic acid and triphenylphosphine present similar cytotoxicity compared to the 16‐electron precursor, with equal cytotoxicity to both A2780 and A2780cisR. Hints at the mechanism of action suggest an apoptotic pathway based on reactive oxygen species (ROS) production. No toxicity was observed in preliminary in vivo pilot studies for these two complexes in subcutaneous A2780 and A2780cisR xenograft models, with some evidence of tumour growth delay.