A Comparative Analysis of the In Vitro Anticancer Activity of Iridium(III) {η5-C5Me4R} Complexes with Variable R Groups.

Piano-stool iridium complexes based on the pentamethylcyclopentadienyl ligand (Cp*) have been intensively investigated as anticancer drug candidates and hold much promise in this setting. A systematic study aimed at outlining the effect of Cp* mono-derivatization on the antiproliferative activity is presented here. Thus, the dinuclear complexes [Ir(η5-C5Me4R)Cl(µ-Cl)]2 (R = Me, 1a; R = H, 1b; R = Pr, 1c; R = 4-C6H4F, 1d; R = 4-C6H4OH, 1e), their 2-phenylpyridyl mononuclear derivatives [Ir(η5-C5Me4R)(kN,kCPhPy)Cl] (2a-d), and the dimethylsulfoxide complex [Ir{η5-C5Me4(4-C6H4OH)}Cl2(κS-Me2S=O)] (3) were synthesized, structurally characterized, and assessed for their cytotoxicity towards a panel of six human and rodent cancer cell lines (mouse melanoma, B16; rat glioma, C6; breast adenocarcinoma, MCF-7; colorectal carcinoma, SW620 and HCT116; ovarian carcinoma, A2780) and one primary, human fetal lung fibroblast cell line (MRC5). Complexes 2b (R = H) and 2d (4-C6H4F) emerged as the most active ones and were selected for further investigation. They did not affect the viability of primary mouse peritoneal cells, and their tumoricidal action arises from the combined influence on cellular proliferation, apoptosis and senescence. The latter is triggered by mitochondrial failure and production of reactive oxygen and nitrogen species.

Ru(ii) water oxidation catalysts with 2,3-bis(2-pyridyl)pyrazine and tris(pyrazolyl)methane ligands: assembly of photo-active and catalytically active subunits in a dinuclear structure.

Two mononuclear Ru(ii) complexes, i.e. [RuCl(κ3N-terpy)(κ2N-dpp)]PF6 ([1]PF6; terpy = 2,2':6',2''-terpyridine; dpp = 2,3-bis(2'-pyridyl-pyrazine) and [RuCl(κ3N-tpm)(κ2N-dpp)]Cl ([2]Cl; tpm = tris(1-pyrazolyl)methane), and one dinuclear complex, i.e. [Ru2Cl(κ3N-tpm)(µ-κ2N:κ2N-dpp)Ru(κ2N-bpy)2][PF6]3 ([3][PF6]3; bpy = 2,2'-bipyridine), have been synthesized and their water oxidation catalytic properties have been investigated. A combined DFT and experimental (35Cl NMR and conductivity measurements) study aimed to elucidate the nature of [1]+ and [2]+ in aqueous solution has also been performed, indicating that one water molecule is allowed to enter the first coordination sphere of [2]+ in the ground state, replacing one tpm nitrogen. Conversely, in the case of [1]+, water coordination, assumed to be needed for the water oxidation process, presumably occurs following the oxidation of the metal. For all complexes, a catalytic wave has been detected in acetonitrile/water 1 : 1 (v/v) solution in the range 1.4-1.7 V vs. SCE. In all cases, water oxidation (investigated at pH < 8) takes place initially via a proton-coupled two-electron, two-proton process with the formation of an Ru(iv)[double bond, length as m-dash]O moiety, followed by one electron oxidation and water nucleophilic attack. The TON and TOF values (within the range of 16-33 and 1.3-2.2 h-1, respectively) of the complexes are higher than those of the benchmark [Ru(LLL)(LL)(OH2)]2+-type species (LLL and LL are tridentate and bidentate polypyridine ligands, respectively), which is [Ru(terpy)(bpm)(OH2)]2+.

A biotin-conjugated photo-activated CO-releasing molecule (biotinCORM): efficient CO-release from an avidin-biotinCORM protein adduct.

Biotinylated pharmaceuticals are of great interest due to the strong interactions between biotinyl-functionality and streptavidin/avidin, which opens up avenues for efficient targeting and localisation. Three new carbon monoxide-releasing molecules (CO-RMs) have been synthesised and characterised using chemical and biological analysis. An alkyne-containing CO-RM 2 was found to be toxic to RAW 264.7 murine macrophages; and thus therapeutically viable CO-RM 1 was employed as the alkyne precursor for [3 + 2] cycloaddition chemistry enabling a new acid-containing CO-RM 4 and biotin-bioconugate-CO-RM (BiotinCORM 5) to be prepared. CO-RM 4 showed significantly improved solubility and BiotinCORM 5 acts as a photo-CO-RM. We have found that an avidin-CORM adduct of 5 is a CO-releasing protein, releasing CO on irradiation with light (400 nm). The avidin-biotinCORM adduct of 5 was found to have a binding energy of 10 kcal mol-1.

A general strategy to add diversity to ruthenium arene complexes with bioactive organic compounds via a coordinated (4-hydroxyphenyl)diphenylphosphine ligand.

Esterification of (4-hydroxyphenyl)diphenylphosphine, coordinated to the [Ru(η6-p-cymene)Cl2] fragment, allows a series of bioactive carboxylic acids to be introduced directly into the organometallic molecule. Evaluation of the compounds on human ovarian cancer cells reveals synergistic enhancements in their antiproliferative activity relative to their bioactive organic and organometallic precursors.