Hydrolysis of an organometallic cation, [Ru(η⁶-p-cym)(H₂O)₃]²⁺ (p-cym = 1-isopropyl-4-methylbenzene), in the presence of 0.20 M KNO₃ or KCl as supporting electrolyte was studied in detail with the combined use of pH-potentiometry, ¹H-NMR, UV-VIS and ESI-TOF-MS. Stoichiometry and stability constants of chlorido, hydroxido and mixed chlorido-hydroxido complexes formed in aqueous solution have been determined. At pH < 4.0 where hydrolysis of [Ru(η⁶-p-cym)(H₂O)₃]²⁺ is negligible with increasing chloride ion concentration two chlorido complexes, [Ru(η⁶-p-cym)(H₂O)₂Cl]⁺ and [{Ru(η⁶-p-cym)}₂(μ²-Cl)₃]⁺, are detectable. At pH > 5.0, in chloride ion free samples the exclusive formation of [{Ru(η⁶-p-cym)}₂(μ²-OH)₃]⁺ is found. However, if chloride ion is present (in the range 0–3.50 M) novel mixed chlorido-hydroxido species, [{Ru(η⁶-p-cym)}₂(μ²-OH)₂(μ²-Cl)]⁺ and [{Ru(η⁶-p-cym)}₂(μ²-OH)(μ²-Cl)₂]⁺ can also be identified at pH > 4.0. The results obtained in this study may help in rationalizing the solution behaviour of half-sandwich [Ru(η⁶-p-cym)(XY)Z] type complexes which, after dissociation of both the monodentate Z and the chelating XY, are capable of yielding the free aqua species [Ru(η⁶-p-cym)(H₂O)₃]²⁺. Our results demonstrate that different chloride ion concentrations can influence the speciation in the acidic pH range but at biologically relevant conditions (pH = 7.4, c_{Cl ⁻} = 0.16 M) and at c_M = 1 μM [{Ru(η⁶-p-cym)}₂(μ²-OH)₃]⁺ is predominant in the absence of any coordinating ligands.

Platinum complexes are used in chemotherapy, primarily as antineoplastic agents. In this study, we assessed the cytotoxic and cytostatic properties of a set of osmium(II), ruthenium(II), iridium(III) and rhodium(III) half-sandwich-type complexes with bidentate monosaccharide ligands. We identified 5 compounds with moderate to negligible acute cytotoxicity but with potent long-term cytostatic activity. These structure-activity relationship studies revealed that: (1) osmium(II) p-cymene complexes were active in all models, while rhodium(III) and iridium(III) Cp* complexes proved largely inactive; (2) the biological effect was influenced by the nature of the central azole ring of the ligands—1,2,3-triazole was the most effective, followed by 1,3,4-oxadiazole, while the isomeric 1,2,4-oxadiazole abolished the cytostatic activity; (3) we found a correlation between the hydrophobic character of the complexes and their cytostatic activity: compounds with O-benzoyl protective groups on the carbohydrate moiety were active, compared to O-deprotected ones. The best compound, an osmium(II) complex, had an IC₅₀ value of 0.70 µM. Furthermore, the steepness of the inhibitory curve of the active complexes suggested cooperative binding; cooperative molecules were better inhibitors than non-cooperative ones. The cytostatic activity of the active complexes was abolished by a lipid-soluble antioxidant, vitamin E, suggesting that oxidative stress plays a major role in the biological activity of the complexes. The complexes were active on ovarian cancer, pancreatic adenocarcinoma, osteosarcoma and Hodgkin’s lymphoma cells, but were inactive on primary, non-transformed human fibroblasts, indicating their applicability as potential anticancer agents.

Novel water soluble half-sandwich complexes of the general formulae [M(η⁶-p-cym)(ha)]₂(CF₃SO₃)₂, [M(η⁶-p-cym)(ha)Cl] or [M(η⁶-p-cym)(ha)(py)]X (M = Os, Ru; ha = hydroxamate; py = pyridine; X = Cl⁻ or CF₃SO₃ ⁻), incorporating metal-containing entities and hydroxamates both with potential anti-proliferative features, were prepared and characterized by elemental analysis, spectroscopy (NMR, IR) and ESI mass spectrometry. The X-ray crystal structure of [Ru(η⁶-p-cym)(μ-meaha)]₂(CF₃SO₃)₂ (5), [Os(η⁶-p-cym)(meaha)Cl] (6), [Ru(η⁶-p-cym)(phebha)Cl], (9), [Ru(η⁶-p-cym)(bha)(py)](CF₃SO₃) (12) and [Ru(η⁶-p-cym)(phebha)(py)](CF₃SO₃) (14), 6 is the first published structure of an organometallic Os(II)-hydroxamate reported. The effect of size differences of the metal ions, the steric demand of the R_C and R_N substituents at the hydroxamate group and the type of the monodentate ligand co-present in the stoichiometry, along with the binding architecture of the half-sandwich metal(II) hydroxamate complexes are discussed. A novel dinuclear, dihydroxo bridged complex [Os(η⁶-p-cym)(py)(μ-OH)]₂(CF₃SO₃)₂ (16) is prepared and characterized by X-ray crystallography. Unexpected formation of a dinuclear oxo bridged Os^II/Os^VI complex [{Os(η⁶-p-cym)(meaha)}(μ-O){Os(O)(meaha)₂}]Cl (17) occurs, and the crystal and molecular structure has been determined by X-ray method. Complexes 1, 5–8, 10 and 14 were tested for their in vitro cytotoxicity, using human-derived ovarian cancer cell lines (A2780 and A2780 cisR), and showed no anti-proliferative effect in the concentration range (0–200 μM) studied.

Hypoxia activated Co(III) complexes as prodrugs may provide with a selective delivery of cytotoxic or antibacterial compounds. Whithin this field sixteen novel Co(III) ternary complexes with the general formula [Co(4N)(flav)](ClO4)2, where 4N = tris(2-aminoethyl)amine (tren) or tris(2-pyridylmethyl)amine (tpa) and flav = deprotonated form of differently substituted flavonols have been synthesized, characterized, and their cytotoxicity assayed under both normoxic and hypoxic conditions. Molecular structures of two free flavonols and seven complexes are also reported. In all the complexes the bioligands exhibited the expected (O,O) coordination mode and the complexes showed a slightly distorted octahedral geometry. Cyclic voltammetric studies revealed that both the substituents of the flavonoles and the type of 4N donor ligands had an impact on the reduction potential of the complex. The ones containing tren demonstrated significantly higher stability than the tpa analogues, making these former compounds promising candidates for the development of hypoxia-activated prodrug complexes. Tpa complexes showed higher activity against both selected human cancer cell lines (A549, A431) than their free ligand flavonols, indicating that the anticancer activity of the bioligand can be enhanced upon complexation. However, slight hypoxia-selectivity was found only for a tren complex (11) with moderate cytotoxicity.

The copper(II)-directed condensation of amino acids with formaldehyde and nitroethane has produced new open-chain quadridentate ligands stereoselectively and in generally high yield. The free ligands with pendant amine substituents may be isolated by zinc reduction of the copper(II) complexes. The reactions studied employed optically pure L-amino acids with non-co-ordinating side chains, racemic amino acids with non-co-ordinating side chains, amino acid mixtures and β-amino acids. The quadri- and quinquedentate ligands form very stable complexes with transition-metal ions, with their copper(II) complexes being generally stable down to pH ≈ 1. The isolation and spectroscopic properties (UV/VIS, IR, NMR and EPR) of cobalt(III) and copper(II) complexes of some of the amino acid-based ligands are reported. Condensation of racemic and mixed amino acids led to one out of three possible quadridentate ligands, and this stereoselectivity is interpreted based on a model involving the co-ordination of an organic nitro group. This mechanism is supported by qualitative molecular mechanics calculations. The crystal structures of the condensation products with β-alanine, ([Cu(mnp-β-ala)]·5H₂O (mnp-β-ala = 6-methyl-6-nitro-4,8-diazaundecanedioate), and the Zn–HCl reduction product of the condensation with glycine [Cu(Hampgly)Cl]·2H₂O (ampgly = 5-amino-5-methyl-3,7-diazanonanedioate), have been determined. In the former structure the Cu^II is in a distorted trigonal-bipyramidal environment with the fifth site being a co-ordinated carboxylate oxygen from an adjacent molecule, while in the latter Cu^II has a square-pyramidal co-ordination with an apical chloride ligand.