Anticancer Potential of Diruthenium Complexes with Bridging Hydrocarbyl Ligands from Bioactive Alkynols

Diruthenacyclopentenone complexes of the general composition [Ru2Cp2(CO)2{μ-η1:η3-CH═C(C(OH)(R))C(═O)}] (2a-c; Cp = η5-C5H5) were synthesized in 94-96% yields from the reactions of [Ru2Cp2(CO)2{μ-η1:η3-C(Ph)═C(Ph)C(═O)}] (1) with 1-ethynylcyclopentanol, 17α-ethynylestradiol, and 17-ethynyltestosterone, respectively, in toluene at reflux. Protonation of 2a-c by HBF4 afforded the corresponding allenyl derivatives [Ru2Cp2(CO)3{μ-η1:η2-CH═C═R}]BF4 (3a-c) in 85-93% yields. All products were thoroughly characterized by elemental analysis, mass spectrometry, and IR, UV-vis, and nuclear magnetic resonance spectroscopy. Additionally, 2a and 3a were investigated by cyclic voltammetry, and the single-crystal diffraction method was employed to establish the X-ray structures of 2b and 3a. The cytotoxicity in vitro of 2b and 3a-c was evaluated against nine human cancer cell lines (A2780, A2780R, MCF-7, HOS, A549, PANC-1, Caco-2, PC-3, and HeLa), while the selectivity was assessed on normal human lung fibroblast (MRC-5). Overall, complexes exert stronger cytotoxicity than cisplatin, and 3b (comprising 17α-estradiol derived ligand) emerged as the best-performing complex. Inductively coupled plasma mass spectrometry cellular uptake studies in A2780 cells revealed a higher level of internalization for 3b and 3c compared to 2b, 3a, and the reference compound RAPTA-C. Experiments conducted on A2780 cells demonstrated a noteworthy impact of 3a and 3b on the cell cycle, leading to the majority of the cells being arrested in the G0/G1 phase. Moreover, 3a moderately induced apoptosis and oxidative stress, while 3b triggered autophagy and mitochondrial membrane potential depletion

Synthesis and studies of aqueous-stable diruthenium aminocarbyne complexes uncovered an N-indolyl derivative as a prospective anticancer agent

We conducted a systematic study on the reactivity of [Ru2Cp2(CO)(4)] (Cp = eta(5)-C5H5) with isocyanides and the subsequent methylation reaction to produce [Ru2Cp2(CO)(2)(mu-CO){mu-CNMe(R)}]+ complexes as CF3SO3- salts, [2a-h]+ [R = Me, cyclohexyl (Cy), 2,6-C6H3Me2 (Xyl), 1H-indol-5-yl, 2-naphthyl, 4-C6H4OMe, (S)-CHMe(Ph), CH2Ph (Bn)]. The resulting products, including five novel ones, underwent structural characterization by IR and multinuclear NMR spectroscopy, with five of them further confirmed via single crystal X-ray diffraction. Compounds [2a-e,h]CF(3)SO(3 )exhibit appreciable water solubility, substantial amphiphilic character and outstanding stability in physiological-like solutions (negligible degradation after 72 hours in DMEM at 37(degrees)C). Representative complexes [2b](+) and [2c](+ )were additionally characterized through cyclic voltammetry in CH2Cl2 and in aqueous phosphate buffer solution. Compounds [2a-d]CF3SO3 were assessed for in vitro cytotoxicity against A2780, A2080R and MCF-7 human cancer cell lines, and [2a-c]CF3SO3 revealed significant-to-moderate cytotoxicity, outperforming cisplatin in several cases. The most favourable IC50 values were observed for [2d]CF3SO3, ranging from 3.7 to 13.0 mu M. Experiments on the noncancerous human cell line MRC-5 highlighted a reasonable selectivity for [2b-d]CF3SO3, with the highest selectivity indexes (SI) calculated as 10.1 (ratio of IC(50 )on MRC-5/IC50 on A2780) and 8.5 (ratio of IC50 on MRC-5/IC(50 )on A2780R) for [2d]CF3SO3. Subsequently, [2d]CF3SO3 was tested across a panel of HOS, A549, PANC1, CaCo2, PC3 and HeLa cancer cells, showing variable cytotoxicity with IC50 values in the range of 9.7 to 20.3 mu M. The cellular effects of [2d](+ )on A2780 cells were investigated using flow cytometry assays, focusing on the cell cycle modification, time-resolved cellular uptake, intracellular ROS production, mitochondrial membrane depolarization, induction of cell death through apoptosis, activation of caspases 3/7 and induction of autophagy. Overall, the results suggest a diphasic mechanism of action for [2d]+, inducing metabolic stress and arresting proliferation in the first/fast phase, followed by the induction of apoptosis and autophagy in the second/slower phase

Carboranedithiols: Building Blocks for Self-Assembled Monolayers on Copper Surfaces

Two different positional isomers of 1,2-dicarba-<i>closo</i>-dodecaboranedithiols, 1,2-(HS)₂-1,2-C₂B₁₀H₁₀ (<b>1</b>) and 9,12-(HS)₂-1,2-C₂B₁₀H₁₀ (<b>2</b>), have been investigated as cluster building blocks for self-assembled monolayers (SAMs) on copper surfaces. These two isomers represent a convenient system in which the attachment of SH groups at different positions on the skeleton affects their acidic character and thus also determines their reactivity with a copper surface. Isomer <b>1</b> exhibited etching of polycrystalline Cu films, and a detailed investigation of the experimental conditions showed that both the acidic character of SH groups and the presence of oxygen at the copper surface play crucial roles in how the surface reaction proceeds: whether toward a self-assembled monolayer or toward copper film etching. We found that each positional isomer requires completely different conditions for the preparation of a SAM on copper surfaces. Optimized conditions for the former isomer required the exposure of a freshly prepared Cu surface to vapor of <b>1</b> in vacuum, which avoided the presence of oxygen and moisture. Adsorption from a dichloromethane solution afforded a sparsely covered Cu(0) surface; isomer <b>1</b> effectively removes the surface copper­(I) oxide, forming a soluble product, but apparently binds only weakly to the clean Cu(0) surface. In contrast, adsorption of the latter, less volatile isomer proceeded better from a dichloromethane solution than from the vapor phase. Isomer <b>2</b> was even able to densely cover the copper surface cleaned up by the dichloromethane solution of <b>1</b>. Both isomers exhibited high capacity to remove oxygen atoms from the surface copper­(I) oxide that forms immediately after the exposure of freshly prepared copper films to ambient atmosphere. Isomer <b>2</b> showed suppression of Cu film oxidation. A number of methods including X-ray photoelectron spectroscopy (XPS), X-ray Rutherford back scattering (RBS), proton-induced X-ray emission (PIXE) analysis, atomic force microscopy (AFM), cyclic voltammetry, and contact angle measurements were used to investigate the experimental conditions for the preparation of SAMs of both positional isomers on copper surfaces and to shed light on the interaction between these molecules and a polycrystalline copper surface