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

Single-Shot Aspect Ratio and Orientation Imaging of Nanoparticles

Plasmonic nanoparticles with surface plasmon resonance (SPR) and scattering response dependent on their geometry and surrounding environment are predestinated to be used as optical probes for sensing and imaging. Optical microscopy is capable of observing nanoparticles in various media, but their geometry remains hidden below the diffraction limit. Here, a wide-field optical imaging technique is demonstrated, restoring the aspect ratio and orientation of individual nanoparticles via the polarization anisotropy (PA) measurement of the scattered light. The PA is mapped into a single nanoparticle image, formed by decomposing the scattered light into longitudinal and transverse SPR modes and manipulating their angular momentum. The wide-field images provide the aspect ratio and orientation of many deposited nanoparticles allowing their assessment in heterogeneous suspensions or time-resolved measurements. In calibration experiments, orientation measurement accuracy and excellent sensitivity to nanoparticles with specific aspect ratios are demonstrated. Subsequently, the method is deployed in the automatic shape-dependent categorization of hundreds of nanoparticles in a heterogeneous mixture. The single-shot capability is demonstrated in the time-resolved imaging of the electrophoretic deposition process