Ligands involved in organometallic chemistry have been functionalised at locations somewhat removed from the binding site for diverse reasons, including modification of electronic and steric characteristics, improving solubility, to confer chirality, to add a spectroscopic "handle", to facilitate electron-transfer processes or for spin-labelling. Here, the focus is specifically on catalytically active metal complexes in which a charged or highly polar group has been appended to the periphery of one or more of the ligands. For the most part, the motivation has been to alter the solubility properties of the catalytic metal complex to which it is attached, for the purposes of immobilisation in another phase (water, ionic liquids, etc.) and improvement of the green credentials of the process. However, other uses are also becoming recognised, for example to aid in situ analysis of catalysts by electrospray ionisation mass spectrometry.

New triruthenium-carbonyl clusters derivatized with glucose-modified bicyclophosphite ligands have been synthesized. These compounds were found to have cytostatic and cytotoxic activity and depending on the number of bicyclophosphite ligands, and could be tuned for either anti-cancer or specific anti-angiogenic activity. While some compounds had a broad cellular toxicity profile in several cell types others showed endothelial cell specific dose-dependent anti-proliferative and anti-migratory efficacy. A profound inhibition of angiogenesis was also observed in the in vivo chicken chorioallantoic membrane (CAM) model, and consequently, these new compounds have considerable potential in drug design, e.g. for the treatment of cancer.T he development of metal-based anti-cancer compounds has traditionally focused on cytotoxic platinumbased compounds, several of which are widely applied in the clinic [1][2][3] . In recent years, however, there has been increasing interest in the development of ruthenium-based anticancer compounds that appear to operate via very different mechanisms, as compared to the clinically used platinum drugs [4][5][6] . Indeed, ruthenium complexes tend to be less cytotoxic towards cancer cells in vitro and their propensity to bind DNA is lower. Two ruthenium compounds, indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)]), termed KP1019 7 , and imidazolium trans-[tetrachloro(dimethylsulfoxide)(1H-imidazole)ruthenate(III)]), termed NAMI-A 8 , are presently in phase II clinical trials, the latter compound showing both anti-metastatic and anti-angiogenic activity in preclinical models. We recently found that a very different type of ruthenium compound, organometallic ruthenium(II) complexes, [Ru(g 6 -arene)Cl 2 (PTA)] (arene 5 toluene and pcymene, PTA 5 1,3,5-triaza-7-phosphaadamantane), also exhibit anti-metastatic 9 and anti-angiogenic 10 properties. Indeed, the effect of these small molecules was at least equivalent to that of sunitinib/SutentH or sorafenib/NaxavarH, clinically used tyrosine kinase inhibitors with anti-angiogenic properties 11 . The promising activities of the ruthenium compounds dictate the need for information on their biomolecular targets and suggests a clinical relevance. In this respect a large number of ruthenium compounds have been evaluated in vitro although classical in vitro cytotoxicity screens have proven, in the past, not to be particularly informative of in vivo activity 4,12 . While most ruthenium-based compounds that have been evaluated as putative anti-cancer agents are mononuclear species with the central ruthenium ion in the 21 or 31 oxidation states, a few studies describing the in vitro activity of ruthenium(0) and osmium (0) clusters have been published 13,14 . Many of these cluster compounds contain carbon monoxide (CO) and/or other ligands, and notably, the biological importance of CO as an essential mediator of numerous effects, including anti-inflammatory-and anti-proliferative activity, has recently been reported 15 . Indeed, a number of CO rel...

Bisphosphines Ph(2)P(CH(2))(n)PPh(2) (n = 1, 2, 4, 6) may be easily monobenzylated to generate cationic phosphine/phosphonium ligands [Ph(2)P(CH(2))(n)PPh(2)CH(2)Ph](+). These ligands may be doped into a catalytic reaction involving neutral complexes with labile phosphine ligands, and replacement of a neutral phosphine with a charged analogue renders the resulting complex amenable to electrospray ionisation mass spectrometry (ESI-MS). Examination of olefin hydrogenation with Wilkinson's catalyst, RhCl(PPh(3))(3), revealed that this approach yielded rapid identification of all off-cycle solution species as well as catalyst poisons. Reactive intermediates could be generated using collision-induced dissociation (CID) of a triphenylphosphine ligand to make three-coordinate RhClP(2) species, and these react with alkenes in the gas phase to form RhClP(2)(alkene). The solution speciation and gas phase behaviour revealed by ESI-MS match closely to what is already known about the system from kinetic and NMR studies.

A series of thioether-functionalised imidazolium salts have been prepared and characterized. Subsequent reaction of the thioether-functionalised imidazolium salts with iodomethane affords imidazolium-sulfonium salts composed of doubly charged cations and two different anions. Imidazolium-sulfonium salts containing a single anion type are obtained either by a solvent extraction method or by anion exchange. The imidazolium-sulfonium salts undergo a methyl-transfer reaction on exposure to water, giving rise to a new, singly charged imidazolium salt with iodide introduced at the 2-position of the imidazolium ring. Crystal structures of some of the imidazolium-sulfonium salts were determined by X-ray crystallography providing the topology of the interactions between the dications and the anions. Electrospray ionization mass spectrometry and quantum-chemical calculations were used to rationalise the relative strength of these interactions.

The reaction of Wilkinson's catalyst Rh(PPh3)3Cl (1) with 1–2 equiv. of di‐n‐hexylsilane gives rise to a complex mixture of products, which has been analyzed by 31P{1H} NMR and shown to include the hydrido complex Rh(PPh3)3H (3). Continuous sampling of the 1:1 reaction mixture by ESI‐MS provided time‐dependent speciation that tracks the formation of 3 at the expense of the initial silane oxidative addition product [Rh(PPh3)2(Cl)(H){Si(nHex)2H}] (2), the subsequent 1st order disappearance of 3, and the formation of other, minor side‐products. Our results provide insight into established activity of 1 for catalytic dehydrocoupling of di‐n‐hexylsilane, and implicate complex 3 as the active species in this catalysis.