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Molecules (Basel, Switzerland) Nov 2022Self-assembled monolayers (SAMs) of terpyridine-based transition metal (ruthenium and osmium) complexes, anchored to gold substrate via tripodal anchoring groups, have...
Self-assembled monolayers (SAMs) of terpyridine-based transition metal (ruthenium and osmium) complexes, anchored to gold substrate via tripodal anchoring groups, have been investigated as possible redox switching elements for molecular electronics. An electrochemical study was complemented by atomic force microscopy (AFM) and scanning tunneling microscopy (STM) methods. STM was used for determination of the SAM conductance values, and computation of the attenuation factor β from tunneling current-distance curves. We have shown that SAMs of molecules contain larger adlayer structures compared with SAMs of molecules, which are characterized by a large number of almost evenly distributed small islands. Furthermore, upon cyclic voltammetric experimentation, films rearrange to form a smaller number of even larger islands, reminiscent of the Ostwald ripening process. SAMs displayed a higher surface concentration of molecules and lower conductance compared with SAMs. The attenuation factor of films changed dramatically, upon electrochemical cycling, to a higher value. These observations are in accordance with previously reported electron transfer kinetics studies.
Topics: Microscopy, Scanning Tunneling; Microscopy, Atomic Force; Surface Properties; Gold; Oxidation-Reduction
PubMed: 36500413
DOI: 10.3390/molecules27238320 -
Photochemistry and Photobiology Mar 2023Osmium (Os) based photosensitizers (PSs) are a unique class of nontetrapyrrolic metal-containing PSs that absorb red light. We recently reported a highly potent Os(II)...
Osmium (Os) based photosensitizers (PSs) are a unique class of nontetrapyrrolic metal-containing PSs that absorb red light. We recently reported a highly potent Os(II) PS, rac-[Os(phen) (IP-4T)](Cl) , referred to as ML18J03 herein, with light EC values as low as 20 pm. ML18J03 also exhibits low dark toxicity and submicromolar light EC values in hypoxia in some cell lines. However, owing to its longer oligothiophene chain, ML18J03 is not completely water soluble and forms 1-2 μm sized aggregates in PBS containing 1% DMSO. This aggregation causes variability in PDT efficacy between assays and thus unreliable and irreproducible reports of in vitro activity. To that end, we utilized PEG-modified DPPC liposomes (138 nm diameter) and DSPE-mPEG micelles (10.2 nm diameter) as lipid nanoformulation vehicles to mitigate aggregation of ML18J03 and found that the spectroscopic properties important to biological activity were maintained or improved. Importantly, the lipid formulations decreased the interassay variance between the EC values by almost 20-fold, with respect to the unformulated ML18J03 when using broadband visible light excitation (P = 0.0276). Herein, lipid formulations are presented as reliable platforms for more accurate in vitro photocytotoxicity quantification for PSs prone to aggregation (such as ML18J03) and will be useful for assessing their in vivo PDT effects.
Topics: Photosensitizing Agents; Osmium; Light; Liposomes; Lipids; Photochemotherapy
PubMed: 36481983
DOI: 10.1111/php.13756 -
Inorganic Chemistry Dec 2022The search for new scaffolds of medicinal significance combined with molecular shape enhances their innovative potential and continues to attract the attention of...
The search for new scaffolds of medicinal significance combined with molecular shape enhances their innovative potential and continues to attract the attention of researchers. Herein, we report the synthesis, spectroscopic characterization (H and C NMR, UV-vis, IR), ESI-mass spectrometry, and single-crystal X-ray diffraction analysis of a new ring system of medicinal significance, 5,6,7,9-tetrahydro-8-indolo[3,2-]benzazocin-8-one, and a series of derived potential ligands (), as well as ruthenium(II), osmium(II), and copper(II) complexes (, , and ). The stability of compounds in 1% DMSO aqueous solutions has been confirmed by H NMR and UV-vis spectroscopy measurements. The antiproliferative activity of and , , and was evaluated by in vitro cytotoxicity tests against four cancer cell lines (LS-174, HCT116, MDA-MB-361, and A549) and one non-cancer cell line (MRC-5). The lead compounds and its copper(II) complex were 15× and 17×, respectively, more cytotoxic than cisplatin against human colon cancer cell line HCT116. Annexin V-FITC apoptosis assay showed dominant apoptosis inducing potential of both compounds after prolonged treatment (48 h) in HCT116 cells. and were found to induce a concentration- and time-dependent arrest of cell cycle in colon cancer cell lines. Antiproliferative activity of in 3D multicellular tumor spheroid model of cancer cells (HCT116, LS-174) superior to that of cisplatin was found. Moreover, and showed notable inhibition potency against glycogen synthase kinases (GSK-3α and GSK-3β), tyrosine-protein kinase (Src), lymphocyte-specific protein-tyrosine kinase (Lck), and cyclin-dependent kinases (Cdk2 and Cdk5) (IC = 1.4-6.1 μM), suggesting their multitargeted mode of action as potential anticancer drugs.
Topics: Humans; Coordination Complexes; Copper; Cisplatin; Cell Line, Tumor; Glycogen Synthase Kinase 3 beta; Antineoplastic Agents; Heterocyclic Compounds; Colonic Neoplasms; Cell Proliferation
PubMed: 36473464
DOI: 10.1021/acs.inorgchem.2c03134 -
Materials (Basel, Switzerland) Nov 2022The sintering of osmium is critical for the preparation of raw material targets for film coating, which is the main application area of osmium. In order to get a better...
The sintering of osmium is critical for the preparation of raw material targets for film coating, which is the main application area of osmium. In order to get a better understanding of the intrinsic mechanism of densification of osmium, a serial study on the sintering behavior of osmium has been made in this study. By the master sintering curve (MSC) and constant heating rate (CHR) method, the sintering activation energy of nanosized osmium is evaluated to be about 340 kJ/mol, which is higher than most other metals. The density-functional theory calculation indicates the higher energy barrier of the surface atom and vacancy migration and lacking migration tunnel of inner point vacancies. For example, the diffusion of osmium atoms on the surface of particles is mainly limited by Os (1010), which has an energy barrier as high as 1.14 eV, that is higher than the W atom on W (110) of 0.99 eV. The vacancy migration energy barrier inside osmium's grains is higher than 3.0 eV, while that of W is only 1.7 eV. This means that it is more difficult for osmium to achieve a high density compared with W, which is consistent with the experimental results. Accordingly, the proposed strategy provides a new opportunity to design a sintering process for target fabrication with excellent properties for various applications.
PubMed: 36431497
DOI: 10.3390/ma15228011 -
Histochemistry and Cell Biology Mar 2023Since epigenetic modifications differ from cell to cell, detecting the DNA methylation status of individual cells is requisite. Therefore, it is important to conduct...
Since epigenetic modifications differ from cell to cell, detecting the DNA methylation status of individual cells is requisite. Therefore, it is important to conduct "morphology-based epigenetics research", in which the sequence-specific DNA methylation status is observed while maintaining tissue architecture. Here we demonstrate a novel histochemical technique that efficiently shows the presence of a single methylated cytosine in a sequence-dependent manner by applying ICON (interstrand complexation with osmium for nucleic acids) probes. By optimizing the concentration and duration of potassium osmate treatment, ICON probes selectively hybridize to methylated cytosine on tissue sections. Since the elongation process by rolling-circle amplification through the padlock probe and synchronous amplification by the hyperbranching reaction at a constant temperature efficiently amplifies the reaction, it is possible to specifically detect the presence of a single methylated cytosine. Since the ICON probe is cross-linked to the nuclear or mitochondrial DNA of the target cell, subsequent elongation and multiplication reactions proceed like a tree growing in soil with its roots firmly planted, thus facilitating the demonstration of methylated cytosine in situ. Using this novel ICON-mediated histochemical method, detection of the methylation of DNA in the regulatory region of the RANK gene in cultured cells and of mitochondrial DNA in paraffin sections of mouse cerebellar tissue was achievable. This combined ICON and rolling-circle amplification method is the first that shows evidence of the presence of a single methylated cytosine in a sequence-specific manner in paraffin sections, and is foreseen as applicable to a wide range of epigenetic studies.
Topics: Animals; Mice; Cytosine; Paraffin; DNA Methylation; Epigenesis, Genetic; DNA, Mitochondrial
PubMed: 36418613
DOI: 10.1007/s00418-022-02165-2 -
Pharmaceutics Nov 2022Osmium (Os)-based photosensitizers (PSs) exhibit unique broad, red-shifted absorption, favoring PDT activity at greater tissue depths. We recently reported on a potent...
Osmium (Os)-based photosensitizers (PSs) exhibit unique broad, red-shifted absorption, favoring PDT activity at greater tissue depths. We recently reported on a potent Os(II) PS, [Os(phen)(IP-4T)](Cl) (ML18J03) with submicromolar hypoxia activity. ML18J03 exhibits a low luminescence quantum yield of 9.8 × 10 in PBS, which limits its capacity for in vivo luminescence imaging. We recently showed that formulating ML18J03 into 10.2 nm DSPE-mPEG micelles (Mic-ML18J03) increases its luminescence quantum yield by two orders of magnitude. Here, we demonstrate that Mic-ML18J03 exhibits 47-fold improved accumulative luminescence signals in orthotopic AT-84 head and neck tumors. We show, for the first time, that micellar formulation provides up to 11.7-fold tumor selectivity for ML18J03. Furthermore, Mic-ML18J03 does not experience the concentration-dependent quenching observed with unformulated ML18J03 in PBS, and formulation reduces spectral shifting of the emission maxima during PDT (variance = 6.5 and 27.3, respectively). The Mic-ML18J03 formulation also increases the production of reactive molecular species 2-3-fold. These findings demonstrate that micellar formulation is a versatile and effective approach to enable in vivo luminescence imaging options for an otherwise quenched, yet promising, PS.
PubMed: 36365244
DOI: 10.3390/pharmaceutics14112426 -
International Journal of Molecular... Oct 2022Interest in the third-row transition metal osmium and its compounds as potential anticancer agents has grown in recent years. Here, we synthesized the osmium(VI) nitrido...
Interest in the third-row transition metal osmium and its compounds as potential anticancer agents has grown in recent years. Here, we synthesized the osmium(VI) nitrido complex (tpm = [5-(Thien-2-yl)-1H-pyrazol-3-yl]methanol), which exhibited a greater inhibitory effect on the cell viabilities of the cervical, ovarian, and breast cancer cell lines compared with cisplatin. Proteomics analysis revealed that modulates the expression of protein-transportation-associated, DNA-metabolism-associated, and oxidative-stress-associated proteins in HepG2 cells. Perturbation of protein expression activity by the complex in cancer cells affects the functions of the mitochondria, resulting in high levels of cellular oxidative stress and low rates of cell survival. Moreover, it caused G2/M phase cell cycle arrest and caspase-mediated apoptosis of HepG2 cells. This study reveals a new high-valent osmium complex as an anticancer agent candidate modulating protein homeostasis.
Topics: Humans; Osmium; Hep G2 Cells; Proteostasis; Antineoplastic Agents; Apoptosis; Cell Line, Tumor
PubMed: 36361570
DOI: 10.3390/ijms232112779 -
Nature Methods Dec 2022We report the rational engineering of a remarkably stable yellow fluorescent protein (YFP), 'hyperfolder YFP' (hfYFP), that withstands chaotropic conditions that...
We report the rational engineering of a remarkably stable yellow fluorescent protein (YFP), 'hyperfolder YFP' (hfYFP), that withstands chaotropic conditions that denature most biological structures within seconds, including superfolder green fluorescent protein (GFP). hfYFP contains no cysteines, is chloride insensitive and tolerates aldehyde and osmium tetroxide fixation better than common fluorescent proteins, enabling its use in expansion and electron microscopies. We solved crystal structures of hfYFP (to 1.7-Å resolution), a monomeric variant, monomeric hyperfolder YFP (1.6 Å) and an mGreenLantern mutant (1.2 Å), and then rationally engineered highly stable 405-nm-excitable GFPs, large Stokes shift (LSS) monomeric GFP (LSSmGFP) and LSSA12 from these structures. Lastly, we directly exploited the chemical stability of hfYFP and LSSmGFP by devising a fluorescence-assisted protein purification strategy enabling all steps of denaturing affinity chromatography to be visualized using ultraviolet or blue light. hfYFP and LSSmGFP represent a new generation of robustly stable fluorescent proteins developed for advanced biotechnological applications.
Topics: Luminescent Proteins; Microscopy; Green Fluorescent Proteins; Fluorescence Resonance Energy Transfer; Light
PubMed: 36344833
DOI: 10.1038/s41592-022-01660-7 -
Inorganic Chemistry Frontiers Jun 2022We disclose novel amphiphilic ruthenium and osmium complexes that auto-assemble into nanomedicines with potent antiproliferative activity by inhibition of mitochondrial...
We disclose novel amphiphilic ruthenium and osmium complexes that auto-assemble into nanomedicines with potent antiproliferative activity by inhibition of mitochondrial respiration. The self-assembling units were rationally designed from the [M(-cymene)(1,10-phenanthroline)Cl]PF motif (where M is either Ru or Os) with an appended C fatty chain to achieve high cellular activity, nano-assembling and mitochondrial targeting. These amphiphilic complexes block cell proliferation at the sub-micromolar range and are particularly potent towards glioblastoma neurospheres made from patient-derived cancer stem cells. A subcutaneous mouse model using these glioblastoma stem cells highlights one of our C Os nanomedicines as highly successful . Mechanistically, we show that they act as metabolic poisons, strongly impairing mitochondrial respiration, corroborated by morphological changes and damage to the mitochondria. A genetic strategy based on RNAi gave further insight on the potential involvement of microtubules as part of the induced cell death. In parallel, we examined the structural properties of these new amphiphilic metal-based constructs, their reactivity and mechanism.
PubMed: 36311556
DOI: 10.1039/d2qi00423b -
Membranes Oct 2022Liquid membranes based on nanoparticles follow a continuous development, both from obtaining methods and characterization of techniques points of view. Lately, osmium...
Liquid membranes based on nanoparticles follow a continuous development, both from obtaining methods and characterization of techniques points of view. Lately, osmium nanoparticles have been deposited either on flat membranes, with the aim of initiating some reaction processes, or on hollow fiber membranes, with the aim of increasing the contact surface with the phases of the membrane system. This paper presents the obtainment and characterization of a liquid membrane based on osmium nanoparticles (Os-NP) dispersed in decanol (Dol) for the realization of a membrane system with a large contact surface between the phases, but without using a liquid membrane support. The dispersion of osmium nanoparticles in -decanol is carried out by the method of reducing osmium tetroxide with 1-undecenoic acid (UDA). The resulting membrane was characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive spectroscopy analysis (EDAX), thermoanalysis (TG, DSC), Fourier transform infra-red (FTIR) spectroscopy and dynamic light scattering (DLS). In order to increase the mass transfer surface, a design for the membrane system was realized with the dispersion of the membrane through the receiving phase and the dispersion of the source phase through the membrane (DBLM-dispersion bulk liquid membrane). The process performance was tested for the reduction of -nitrophenol (pNP) from the source phase, using sodium tetra-borohydride (NaBH), to -aminophenol (pAP), which was transported and collected in the receiving phase. The obtained results show that membranes based on the dispersion of osmium nanoparticles in -decanol can be used with an efficiency of over 90% for the reduction of -nitrophenol and the separation of -aminophenol.
PubMed: 36295782
DOI: 10.3390/membranes12101024