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Microscopy (Oxford, England) Nov 2023Biological nanoparticles, such as bacterial outer membrane vesicles (OMVs), are routinely characterized through transmission electron microscopy (TEM). In this study, we...
Biological nanoparticles, such as bacterial outer membrane vesicles (OMVs), are routinely characterized through transmission electron microscopy (TEM). In this study, we report a novel method to prepare OMVs for TEM imaging. To preserve vesicular shape and structure, we developed a dual fixation protocol involving osmium tetroxide incubation prior to negative staining with uranyl acetate. Combining osmium tetroxide with uranyl acetate resulted in preservation of sub-50 nm vesicles and improved morphological stability, enhancing characterization of lipid-based nanoparticles by TEM.
Topics: Microscopy, Electron; Coloring Agents; Osmium Tetroxide; Bacterial Outer Membrane; Microscopy, Electron, Transmission; Staining and Labeling; Osmium
PubMed: 37148329
DOI: 10.1093/jmicro/dfad027 -
Coordination Chemistry Reviews Jun 2023The catalytic addition of water to unsaturated C-C or C-N π bonds represent one of the most important and environmentally sustainable methods to form C-O bonds for the...
The catalytic addition of water to unsaturated C-C or C-N π bonds represent one of the most important and environmentally sustainable methods to form C-O bonds for the production of synthetic intermediates, medicinal agents and natural products. The traditional acid-catalyzed hydration of unsaturated compounds typically requires strong acids or toxic mercury salts, which limits practical applications and presents safety and environmental concerns. Today, transition-metal-catalyzed hydration supported by NHC (NHC = N-heterocyclic carbene) ligands has attracted major attention. By rational design of ligands, choice of metals and counterions as well as mechanistic studies and the development of heterogeneous systems, major progress has been achieved for a broad range of hydration processes. In particular, the combination of NHC ligands with gold shows excellent reactivity compared with other catalytic systems; however, other systems based on silver, ruthenium, osmium, platinum, rhodium and nickel have also been discovered. Ancillary NHC ligands provide stabilization of transition metals and ensure high catalytic activity in hydration owing to their unique electronic and steric properties. NHC-Au(I) complexes are particularly favored for hydration of unsaturated hydrocarbons due to soft and carbophilic properties of gold. In this review, we present a comprehensive overview of hydration reactions catalyzed by transition metal-NHC complexes and their applications in catalytic hydration of different classes of π-substrates with a focus on the role of NHC ligands, types of metals and counterions.
PubMed: 37064328
DOI: 10.1016/j.ccr.2023.215110 -
National Science Review Mar 2023Aromatic metallacycles are of considerable current interest. Reported aromatic metallacycles are mainly those with carbon, nitrogen, oxygen and sulfur. In this work, we...
Aromatic metallacycles are of considerable current interest. Reported aromatic metallacycles are mainly those with carbon, nitrogen, oxygen and sulfur. In this work, we report the synthesis and characterization of aromatic chloroosmacyclopentatrienes, which represent the first structurally confirmed metallaaromatic with a chlorine atom in its framework. Single-crystal X-ray diffraction studies show that these planar chloroosmacyclopentatrienes possess a very short Os-ClC distance suggesting M=ClC bond character.
PubMed: 37063704
DOI: 10.1093/nsr/nwac237 -
Molecules (Basel, Switzerland) Mar 2023While platinum-based compounds such as cisplatin form the backbone of chemotherapy, the use of these compounds is limited by resistance and toxicity, driving the...
While platinum-based compounds such as cisplatin form the backbone of chemotherapy, the use of these compounds is limited by resistance and toxicity, driving the development of novel complexes with cytostatic properties. In this study, we synthesized a set of half-sandwich complexes of platinum-group metal ions (Ru(II), Os(II), Ir(III) and Rh(III)) with an N,N-bidentate ligand comprising a -glucosaminyl group and a heterocycle, such as pyridine, pyridazine, pyrimidine, pyrazine or quinoline. The sugar-containing ligands themselves are unknown compounds and were obtained by nucleophilic additions of lithiated heterocycles to -perbenzylated 2-nitro-glucal. Reduction of the adducts and, where necessary, subsequent protecting group manipulations furnished the above -glucosaminyl heterocycles in their -perbenzylated, -perbenzoylated and -unprotected forms. The derived complexes were tested on A2780 ovarian cancer cells. Pyridine, pyrazine and pyridazine-containing complexes proved to be cytostatic and cytotoxic on A2780 cells, while pyrimidine and quinoline derivatives were inactive. The best complexes contained pyridine as the heterocycle. The metal ion with polyhapto arene/arenyl moiety also impacted on the biological activity of the complexes. Ruthenium complexes with -cymene and iridium complexes with Cp* had the best performance in ovarian cancer cells, followed by osmium complexes with -cymene and rhodium complexes with Cp*. Finally, the chemical nature of the protective groups on the hydroxyl groups of the carbohydrate moiety were also key determinants of bioactivity; in particular, -benzyl groups were superior to -benzoyl groups. The IC values of the complexes were in the low micromolar range, and, importantly, the complexes were less active against primary, untransformed human dermal fibroblasts; however, the anticipated therapeutic window is narrow. The bioactive complexes exerted cytostasis on a set of carcinomas such as cell models of glioblastoma, as well as breast and pancreatic cancers. Furthermore, the same complexes exhibited bacteriostatic properties against multiresistant Gram-positive and clinical isolates in the low micromolar range.
Topics: Humans; Female; Coordination Complexes; Cytostatic Agents; Cell Line, Tumor; Ovarian Neoplasms; Antineoplastic Agents; Metals; Azo Compounds; Quinolines; Pyridines; Anti-Infective Agents; Ruthenium
PubMed: 37049820
DOI: 10.3390/molecules28073058 -
Inorganic Chemistry Apr 2023We present the synthesis and characterization of six new heteroleptic osmium(II) complexes of the type [Os(C^N)(N^N)]OTf (N^N = 2,2'-bipyridine and...
We present the synthesis and characterization of six new heteroleptic osmium(II) complexes of the type [Os(C^N)(N^N)]OTf (N^N = 2,2'-bipyridine and dipyrido[3,2-:2',3'-]quinoxaline; C^N = deprotonated methyl 1-butyl-2aryl-benzimidazolecarboxylate) with varying substituents in the R3 position of the phenyl ring of the cyclometalating C^N ligand. The new compounds are highly kinetically inert and absorb a full-wavelength range of visible light. An investigation of the antiproliferative activity of the new compounds has been performed using a panel of human cancer and noncancerous 2D cell monolayer cultures under dark conditions and green light irradiation. The results demonstrate that the new Os(II) complexes are markedly more potent than conventional cisplatin. The promising antiproliferative activity of selected Os(II) complexes was also confirmed using 3D multicellular tumor spheroids, which have the characteristics of solid tumors and can mimic the tumor tissue microenvironment. The mechanism of antiproliferative action of complexes has also been investigated and revealed that the investigated Os(II) complexes activate the endoplasmic reticulum stress pathway in cancer cells and disrupt calcium homeostasis.
Topics: Humans; Structure-Activity Relationship; Osmium; Calcium; Cell Line, Tumor; Benzimidazoles; Homeostasis; Antineoplastic Agents; Coordination Complexes; Neoplasms
PubMed: 37040203
DOI: 10.1021/acs.inorgchem.3c00501 -
Molecules (Basel, Switzerland) Mar 2023Sharpless asymmetric dihydroxylation is an important reaction in the enantioselective synthesis of chiral vicinal diols that involves the treatment of alkene with osmium... (Review)
Review
Sharpless asymmetric dihydroxylation is an important reaction in the enantioselective synthesis of chiral vicinal diols that involves the treatment of alkene with osmium tetroxide along with optically active quinine ligand. Sharpless introduced this methodology after considering the importance of enantioselectivity in the total synthesis of medicinally important compounds. Vicinal diols, produced as a result of this reaction, act as intermediates in the synthesis of different naturally occurring compounds. Hence, Sharpless asymmetric dihydroxylation plays an important role in synthetic organic chemistry due to its undeniable contribution to the synthesis of biologically active organic compounds. This review emphasizes the significance of Sharpless asymmetric dihydroxylation in the total synthesis of various natural products, published since 2020.
Topics: Hydroxylation; Biological Products; Alkenes; Stereoisomerism
PubMed: 36985698
DOI: 10.3390/molecules28062722 -
Journal of Biological Inorganic... Apr 2023Synthetic anticancer catalysts offer potential for low-dose therapy and the targeting of biochemical pathways in novel ways. Chiral organo-osmium complexes, for example,...
Synthetic anticancer catalysts offer potential for low-dose therapy and the targeting of biochemical pathways in novel ways. Chiral organo-osmium complexes, for example, can catalyse the asymmetric transfer hydrogenation of pyruvate, a key substrate for energy generation, in cells. However, small-molecule synthetic catalysts are readily poisoned and there is a need to optimise their activity before this occurs, or to avoid this occurring. We show that the activity of the synthetic organometallic redox catalyst [Os(p-cymene)(TsDPEN)] (1), which can reduce pyruvate to un-natural D-lactate in MCF7 breast cancer cells using formate as a hydride source, is significantly increased in combination with the monocarboxylate transporter (MCT) inhibitor AZD3965. AZD3965, a drug currently in clinical trials, also significantly lowers the intracellular level of glutathione and increases mitochondrial metabolism. These synergistic mechanisms of reductive stress induced by 1, blockade of lactate efflux, and oxidative stress induced by AZD3965 provide a strategy for low-dose combination therapy with novel mechanisms of action.
Topics: Lactic Acid; Neoplasms; Pyruvates; Catalysis
PubMed: 36884092
DOI: 10.1007/s00775-023-01994-3 -
Journal of Nanobiotechnology Mar 2023Treatment of complete loss of skin thickness requires expensive cellular materials and limited skin grafts used as temporary coverage. This paper presents an acellular...
Accelular nanofibrous bilayer scaffold intrapenetrated with polydopamine network and implemented into a full-thickness wound of a white-pig model affects inflammation and healing process.
Treatment of complete loss of skin thickness requires expensive cellular materials and limited skin grafts used as temporary coverage. This paper presents an acellular bilayer scaffold modified with polydopamine (PDA), which is designed to mimic a missing dermis and a basement membrane (BM). The alternate dermis is made from freeze-dried collagen and chitosan (Coll/Chit) or collagen and a calcium salt of oxidized cellulose (Coll/CaOC). Alternate BM is made from electrospun gelatin (Gel), polycaprolactone (PCL), and CaOC. Morphological and mechanical analyzes have shown that PDA significantly improved the elasticity and strength of collagen microfibrils, which favorably affected swelling capacity and porosity. PDA significantly supported and maintained metabolic activity, proliferation, and viability of the murine fibroblast cell lines. The in vivo experiment carried out in a domestic Large white pig model resulted in the expression of pro-inflammatory cytokines in the first 1-2 weeks, giving the idea that PDA and/or CaOC trigger the early stages of inflammation. Otherwise, in later stages, PDA caused a reduction in inflammation with the expression of the anti-inflammatory molecule IL10 and the transforming growth factor β (TGFβ1), which could support the formation of fibroblasts. Similarities in treatment with native porcine skin suggested that the bilayer can be used as an implant for full-thickness skin wounds and thus eliminate the use of skin grafts.
Topics: Swine; Animals; Mice; Nanofibers; Osmium Compounds; Inflammation
PubMed: 36882867
DOI: 10.1186/s12951-023-01822-5 -
Organometallics Aug 2022Complex OsH{κ-,,-[xant(PPr)]} () activates the Si-H bond of triethylsilane, triphenylsilane, and 1,1,1,3,5,5,5-heptamethyltrisiloxane to give the...
Complex OsH{κ-,,-[xant(PPr)]} () activates the Si-H bond of triethylsilane, triphenylsilane, and 1,1,1,3,5,5,5-heptamethyltrisiloxane to give the silyl-osmium(IV)-trihydride derivatives OsH(SiR){κ-,,-[xant(PPr)]} [SiR = SiEt (), SiPh (), SiMe(OSiMe) ()] and H. The activation takes place via an unsaturated tetrahydride intermediate, resulting from the dissociation of the oxygen atom of the pincer ligand 9,9-dimethyl-4,5-bis(diisopropylphosphino)xanthene (xant(PPr)). This intermediate, which has been trapped to form OsH{κ-,-[xant(PPr)]}(PPr) (), coordinates the Si-H bond of the silanes to subsequently undergo a homolytic cleavage. Kinetics of the reaction along with the observed primary isotope effect demonstrates that the Si-H rupture is the rate-determining step of the activation. Complex reacts with 1,1-diphenyl-2-propyn-1-ol and 1-phenyl-1-propyne. The reaction with the former affords Os{C≡CC(OH)Ph}{=C=CHC(OH)Ph}{κ-,,-[xant(PPr)]} (), which catalyzes the conversion of the propargylic alcohol into ()-2-(5,5-diphenylfuran-2()-ylidene)-1,1-diphenylethan-1-ol, via ()-enynediol. In methanol, the hydroxyvinylidene ligand of dehydrates to allenylidene, generating Os{C≡CC(OH)Ph}{=C=C=CPh}{κ-,,-[xant(PPr)]} (). The reaction of with 1-phenyl-1-propyne leads to OsH{κ-C,η-[CHCHCH=CH]}{κ-,,-[xant(PPr)]} () and PhCHCH=CH(SiEt).
PubMed: 36866234
DOI: 10.1021/acs.organomet.2c00201 -
Organometallics Sep 2022Reactions of the hexahydride OsH(PPr) () with 2-butyne and 3-hexyne and the behavior of the resulting species toward pinacolborane (pinBH) have been investigated in the...
Reactions of the hexahydride OsH(PPr) () with 2-butyne and 3-hexyne and the behavior of the resulting species toward pinacolborane (pinBH) have been investigated in the search for new hydroboration processes. Complex reacts with 2-butyne to give 1-butene and the osmacyclopropene OsH(η-CMe)(PPr) (). In toluene, at 80 °C, the coordinated hydrocarbon isomerizes into a η-butenediyl form to afford OsH(η-CHCHCHCH)(PPr) (). Isotopic labeling experiments indicate that the isomerization involves Me-to-C hydrogen 1,2-shifts, which take place through the metal. The reaction of with 3-hexyne gives 1-hexene and OsH(η-CEt)(PPr) (). Similarly to , complex evolves to η-butenediyl derivatives OsH(η-CHCHCHCHEt)(PPr) () and OsH(η-MeCHCHCHCHMe)(PPr) (). In the presence of pinBH, complex generates 2-pinacolboryl-1-butene and OsH{κ-,-(HBpin)}(η-HBpin)(PPr) (). According to the formation of the borylated olefin, complex is a catalyst precursor for the migratory hydroboration of 2-butyne and 3-hexyne to 2-pinacolboryl-1-butene and 4-pinacolboryl-1-hexene. During the hydroboration, complex is the main osmium species. The hexahydride also acts as a catalyst precursor, but it requires an induction period that causes the loss of 2 equiv of alkyne per equiv of osmium.
PubMed: 36864948
DOI: 10.1021/acs.organomet.2c00338