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Molecules (Basel, Switzerland) Sep 2021Metal complexes have been used to treat cancer since the discovery of cisplatin and its interaction with DNA in the 1960's. Facing the resistance mechanisms against... (Review)
Review
Bypassing the Resistance Mechanisms of the Tumor Ecosystem by Targeting the Endoplasmic Reticulum Stress Pathway Using Ruthenium- and Osmium-Based Organometallic Compounds: An Exciting Long-Term Collaboration with Dr. Michel Pfeffer.
Metal complexes have been used to treat cancer since the discovery of cisplatin and its interaction with DNA in the 1960's. Facing the resistance mechanisms against platinum salts and their side effects, safer therapeutic approaches have been sought through other metals, including ruthenium. In the early 2000s, Michel Pfeffer and his collaborators started to investigate the biological activity of organo-ruthenium/osmium complexes, demonstrating their ability to interfere with the activity of purified redox enzymes. Then, they discovered that these organo-ruthenium/osmium complexes could act independently of DNA damage and bypass the requirement for the tumor suppressor gene to induce the endoplasmic reticulum (ER) stress pathway, which is an original cell death pathway. They showed that other types of ruthenium complexes-as well complexes with other metals (osmium, iron, platinum)-can induce this pathway as well. They also demonstrated that ruthenium complexes accumulate in the ER after entering the cell using passive and active mechanisms. These particular physico-chemical properties of the organometallic complexes designed by Dr. Pfeffer contribute to their ability to reduce tumor growth and angiogenesis. Taken together, the pioneering work of Dr. Michel Pfeffer over his career provides us with a legacy that we have yet to fully embrace.
Topics: Animals; Antineoplastic Agents; Drug Resistance, Neoplasm; Endoplasmic Reticulum Stress; Humans; Organometallic Compounds; Osmium; Ruthenium
PubMed: 34500819
DOI: 10.3390/molecules26175386 -
Analytical Chemistry Jan 2022Efficient simultaneous photochemical vapor generation (PVG) of ruthenium (Ru) and osmium (Os) in the medium of formic acid was demonstrated. A flow-through photoreactor...
Efficient simultaneous photochemical vapor generation (PVG) of ruthenium (Ru) and osmium (Os) in the medium of formic acid was demonstrated. A flow-through photoreactor hyphenated to an inductively coupled plasma-mass spectrometer (ICP-MS) was used for the PVG and subsequent detection of the two elements. A similar synergistic enhancement from cobalt and cadmium ions on the PVG efficiency of both Ru and Os was discovered. Following the critical evaluation of the impacts of various transition metal ions, the concentrations of formic acid, cobalt, and cadmium ions, the flow rate of carrier gas, and the UV irradiation time, impressive limits of detection (LODs) of 5 and 0.5 ng L were achieved for Ru and Os, respectively. The accuracy of the proposed PVG-ICP-MS method was validated by the analysis of several water samples with desirable spike recoveries obtained. Furthermore, the volatile compounds of Ru were directed and cryogenically trapped in acetonitrile and generation of carbonyls of Ru was verified by high-resolution electrospray ionization-mass spectra (ESI-MS).
Topics: Cobalt; Gases; Osmium; Ruthenium; Spectrometry, Mass, Electrospray Ionization
PubMed: 34931811
DOI: 10.1021/acs.analchem.1c03357 -
Angewandte Chemie (International Ed. in... Sep 2022Targeting metabolic reprogramming to treat cancer could increase overall survival and reduce side effects. Here, we put forward a strategy using...
Targeting metabolic reprogramming to treat cancer could increase overall survival and reduce side effects. Here, we put forward a strategy using arene-ruthenium(II)/osmium(II) complexes to potentiate the anticancer effect of metformin (Met.) via glucose metabolism reprogramming. Complexes 1-6 with oxoglaucine derivatives as ligands were synthesized and their anti-tumor activities were tested under hypoglycemia. Results indicated that 2 and 5 potentiated the anticancer effects of Met. under hypoglycemia, exhibiting lower toxicity, slower blood glucose decline and inhibition of early tumor liver metastasis. Combination of 5 with Met. could be used as a new strategy to treat cancer under hypoglycemia through glucose metabolism reprogramming.
Topics: Antineoplastic Agents; Cell Line, Tumor; Coordination Complexes; Glucose; Humans; Hypoglycemia; Metformin; Organometallic Compounds; Osmium; Ruthenium
PubMed: 35900359
DOI: 10.1002/anie.202208570 -
Angewandte Chemie (International Ed. in... Dec 2021Herein, we disclose osmaelectrocatalyzed C-H activations that set the stage for electrooxidative alkyne annulations by benzoic acids. The osmium electrocatalysis enables...
Herein, we disclose osmaelectrocatalyzed C-H activations that set the stage for electrooxidative alkyne annulations by benzoic acids. The osmium electrocatalysis enables site- and chemoselective electrooxidative C-H activations with unique levels of selectivity. The isolation of unprecedented osmium(0) and osmium(II) intermediates, along with crystallographic characterization and analyses by spectrometric and spectroscopic in operando techniques delineate a synergistic osmium redox catalyst regime. Detailed mechanistic studies revealed a facile C-H cleavage, which allows for an ample substrate scope, providing provide robust and user-friendly access to annulated heterocycles.
PubMed: 34665924
DOI: 10.1002/anie.202110616 -
International Journal of Molecular... Jun 2022(1) Background: Since the discovery of cisplatin’s cytotoxic properties, platinum(II) compounds have attracted much interest in the field of anticancer drug...
Novel Nickel(II), Palladium(II), and Platinum(II) Complexes with , Bidendate Cinnamic Acid Ester Derivatives: An In Vitro Cytotoxic Comparison to Ruthenium(II) and Osmium(II) Analogues.
(1) Background: Since the discovery of cisplatin’s cytotoxic properties, platinum(II) compounds have attracted much interest in the field of anticancer drug development. Over the last few years, classical structure−activity relationships (SAR) have been broken by some promising new compounds based on platinum or other metals. We focus on the synthesis and characterization of 17 different complexes with β-hydroxydithiocinnamic acid esters as O,S bidendate ligands for nickel(II), palladium(II), and platinum(II) complexes. (2) Methods: The bidendate compounds were synthesized and characterized using classical methods including NMR spectroscopy, MS spectrometry, elemental analysis, and X-ray crystallography, and their cytotoxic potential was assessed using in vitro cell culture assays. Data were compared with other recently reported platinum(II), ruthenium(II), and osmium(II) complexes based on the same main ligand system. (3) Results: SAR analyses regarding the metal ion (M), and the alkyl-chain position (P) and length (L), revealed the following order of the effect strength for in vitro activity: M > P > L. The highest activities have Pd complexes and ortho-substituted compounds. Specific palladium(II) complexes show lower IC50 values compared to cisplatin, are able to elude cisplatin resistance mechanisms, and show a higher cancer cell specificity. (4) Conclusion: A promising new palladium(II) candidate (Pd3) should be evaluated in further studies using in vivo model systems, and the identified SARs may help to target platinum-resistant tumors.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cinnamates; Cisplatin; Coordination Complexes; Esters; Ligands; Nickel; Osmium; Palladium; Platinum; Ruthenium
PubMed: 35743112
DOI: 10.3390/ijms23126669 -
Microscopy (Oxford, England) Oct 2023Correlative fluorescent and electron microscopic images of the same section of epoxy (or other polymer)-embedded samples, hereafter referred to as 'in-resin CLEM', have...
Correlative fluorescent and electron microscopic images of the same section of epoxy (or other polymer)-embedded samples, hereafter referred to as 'in-resin CLEM', have been developed to improve the positional accuracy and Z-axis resolution limitations of conventional correlative light and electron microscopy (CLEM). High-pressure freezing and quick-freezing substitution result in in-resin CLEM of acrylic-based resin-embedded cells expressing green fluorescent protein, yellow fluorescent protein, mVenus and mCherry, which are sensitive to osmium tetroxide. The identification of osmium-resistant fluorescent proteins leads to the development of in-resin CLEM of Epon-embedded cells. Using subtraction-based fluorescence microscopy with a photoconvertible fluorescent protein, mEosEM-E, its green fluorescence can be observed in thin sections of Epon-embedded cells, and two-color in-resin CLEM using mEosEM-E and mScarlet-H can be performed. Green fluorescent proteins, CoGFP variant 0 and mWasabi, and far-red fluorescent proteins, mCherry2 and mKate2, are available for in-resin CLEM of Epon-embedded cells using the standard procedure for Epon-embedding with additional incubation. Proximity labeling is applied to in-resin CLEM to overcome the limitations of fluorescent proteins in epoxy resin. These approaches will contribute significantly to the future of CLEM analysis.
Topics: Humans; Epoxy Resins; Microscopy, Electron; Microscopy, Fluorescence; Green Fluorescent Proteins; HeLa Cells
PubMed: 37217182
DOI: 10.1093/jmicro/dfad028 -
Macromolecular Rapid Communications Nov 2018This work presents the preparation of a series of novel Os(II)-based metallo-supramolecular polymers (polyOss: linear polyOsL1 and hyperbranched polyOsL1 L2 ) that show...
This work presents the preparation of a series of novel Os(II)-based metallo-supramolecular polymers (polyOss: linear polyOsL1 and hyperbranched polyOsL1 L2 ) that show a broad absorption spanning 312 to 677 nm and a low Os(II)/(III) redox potential of 0.94 V. The electrochromic properties of a polyOs film cast on an ITO substrate is investigated. The change in transmittance (ΔT) of polyOsL1 is 49.9%, and the switching times for coloration (t ) and bleaching (t ) are 0.70 and 0.82 s, respectively. The introduction of a 10% branching structure (polyOsL1 L2 ) further enhanced the electrochromic performance with ΔT = 59.4%, t = 0.41 s, and t = 0.54 s. The coloration efficiency (η) increased from 396.1 to 467.5 cm C upon branching. A solid-state electrochromic device with polyOsL1 is successfully fabricated to use the polymer for potential applications.
Topics: Electrochemical Techniques; Macromolecular Substances; Molecular Structure; Organometallic Compounds; Osmium Compounds; Particle Size; Polymers; Surface Properties
PubMed: 30062769
DOI: 10.1002/marc.201800415 -
Cytometry. Part a : the Journal of the... Feb 2017
Topics: Animals; Biomarkers; Flow Cytometry; Humans
PubMed: 28141893
DOI: 10.1002/cyto.a.23034 -
Biomedical Research (Tokyo, Japan) 2020The osmium maceration method is a powerful technique for observing the three-dimensional ultrastructure of cellular organelles by scanning electron microscopy. In the...
The osmium maceration method is a powerful technique for observing the three-dimensional ultrastructure of cellular organelles by scanning electron microscopy. In the conventional osmium maceration method, tissues are immersed in a diluted osmium tetroxide solution for several days at 20°C to remove soluble cytosolic proteins from the freeze-cracked surface of cells, and the optimal duration of this process is dependent on the cell type. To improve the efficiency of the osmium maceration procedure, we have examined systematically the relationship between the reaction temperature and time of the osmium maceration procedure. Treatment at temperatures higher than 20°C drastically shortened the time required to remove cytosolic proteins from the freeze-cracked surface of specimens with optimal durations for the osmium maceration of hepatocytes at 30, 40, 50 and 60°C being 30, 15, 5 and 1 h, respectively. Considering the stability and reproducibility of the macerated specimens, we concluded that the most appropriate temperature was 30 to 40°C. This rapid osmium maceration procedure was used successfully to observe the 3D ultrastructure of Purkinje cells in the cerebellum and proximal convoluted tubule cells in the kidney. This simple and reproducible rapid osmium maceration protocol should find wide appeal for the 3D analysis of cellular organelles in various cell types.
Topics: Animals; Cryopreservation; Cryoprotective Agents; Dimethyl Sulfoxide; Formaldehyde; Glutaral; Hepatocytes; Liver; Male; Microscopy, Electron, Scanning; Osmium Tetroxide; Polymers; Rats; Rats, Wistar; Temperature; Time Factors; Tissue Fixation
PubMed: 32801265
DOI: 10.2220/biomedres.41.161 -
Journal of the Electrochemical Society Jan 2022Electrochemical sensors that utilize enzymes are a sensitive, inexpensive means of detecting biologically relevant analytes. These sensors are categorized based on their...
Electrochemical sensors that utilize enzymes are a sensitive, inexpensive means of detecting biologically relevant analytes. These sensors are categorized based on their construction and method of signal transport. Type I sensors consist of a crosslinked enzyme on an electrode surface and are potentially subject to interference from byproducts and other biological analytes. However, type II sensors help alleviate this problem with the addition of a redox polymer layer that assists in signal transduction, thus minimizing interferences. An osmium-loaded poly(vinylimidazole) polymer (Os-PVI) is commonly used with successful results, and when combined with an enzyme yields a type II sensor. Our initial attempts at the synthesis of this polymer resulted in an unexpected osmium precursor, which had fluorescent and redox properties that did not match with the desired Os-PVI polymer. Careful exclusion of oxygen during the Os complex precursor synthesis was necessary to avoid this unexpected oxygen containing Os-precursor, which had been seen previously in mass spectrometry studies. All precursors and osmium polymers were characterized with H NMR, fluorescence, mass spectrometry, and cyclic voltammetry to provide a better understanding of these compounds and assist in the building of new sensors.
PubMed: 35692370
DOI: 10.1149/1945-7111/ac42a0