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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 -
Frontiers in Chemistry 2023The toxicity of and resistance to platinum complexes as cisplatin, oxaliplatin or carboplatin calls for the replacement of these therapeutic agents in clinical settings....
Half sandwich-type osmium, ruthenium, iridium and rhodium complexes with bidentate glycosyl heterocyclic ligands induce cytostasis in platinum-resistant ovarian cancer cells and bacteriostasis in Gram-positive multiresistant bacteria.
The toxicity of and resistance to platinum complexes as cisplatin, oxaliplatin or carboplatin calls for the replacement of these therapeutic agents in clinical settings. We have previously identified a set of half sandwich-type osmium, ruthenium and iridium complexes with bidentate glycosyl heterocyclic ligands exerting specific cytostatic activity on cancer cells but not on non-transformed primary cells. The apolar nature of the complexes, conferred by large, apolar benzoyl protective groups on the hydroxyl groups of the carbohydrate moiety, was the main molecular feature to induce cytostasis. We exchanged the benzoyl protective groups to straight chain alkanoyl groups with varying length (3 to 7 carbon units) that increased the IC value as compared to the benzoyl-protected complexes and rendered the complexes toxic. These results suggest a need for aromatic groups in the molecule. The pyridine moiety of the bidentate ligand was exchanged for a quinoline group to enlarge the apolar surface of the molecule. This modification decreased the IC value of the complexes. The complexes containing [(η--cymene)Ru(II)], [(η--cymene)Os(II)] or [(η-Cp*)Ir(III)] were biologically active unlike the complex containing [(η-Cp*)Rh(III)]. The complexes with cytostatic activity were active on ovarian cancer (A2780, ID8), pancreatic adenocarcinoma (Capan2), sarcoma (Saos) and lymphoma cell lines (L428), but not on primary dermal fibroblasts and their activity was dependent on reactive oxygen species production. Importantly, these complexes were cytostatic on cisplatin-resistant A2780 ovarian cancer cells with similar IC values as on cisplatin-sensitive A2780 cells. In addition, the quinoline-containing Ru and Os complexes and the short chain alkanoyl-modified complexes (C3 and C4) proved to be bacteriostatic in multiresistant Gram-positive and isolates. Hereby, we identified a set of complexes with submicromolar to low micromolar inhibitory constants against a wide range of cancer cells, including platinum resistant cells and against multiresistant Gram-positive bacteria.
PubMed: 36793764
DOI: 10.3389/fchem.2023.1086267 -
Molecules (Basel, Switzerland) Feb 2023Two novel heterobimetallic compounds {[Mn(SB)M(CN)]·4HO} (SB = N,N'-ethylenebis(5-trimethylammoniomethylsalicylideneiminate) based on orbitally degenerate...
Two novel heterobimetallic compounds {[Mn(SB)M(CN)]·4HO} (SB = N,N'-ethylenebis(5-trimethylammoniomethylsalicylideneiminate) based on orbitally degenerate cyanidometallates [Os(CN)] () and [Ru(CN)] () and Mn Schiff base complex were synthesized and characterized structurally and magnetically. Their crystal structures consist of electrically neutral, well-isolated chains composed of alternating [M(CN)] anions and square planar [Mn(SB)] cations bridged by cyanide groups. These -ion magnetic anisotropy of Mn centers. These results indicate that the presence of compounds exhibit single-chain magnet (SCM) behavior with the energy barriers of Δ/ = 73 K, Δ/ = 41.5 K () and Δ/ = 51 K, Δ = 27 K (). Blocking temperatures of = 2.8, 2.1 K and magnetic hysteresis with coercive fields (at 1.8 K) of 8000, 1600 Oe were found for and , respectively. Theoretical analysis of the magnetic data reveals that their single-chain magnet behavior is a product of a complicated interplay of extremely anisotropic triaxial exchange interactions in M(4d/5d)-CN-Mn fragments: ---, with opposite sign of exchange parameters = -22, = +28, = -26 cm and = -18, = +20, = -18 cm in and , respectively) and single orbitally degenerate [Os(CN)] and [Ru(CN)] spin units with unquenched orbital angular momentum in the chain compounds and leads to a peculiar regime of slow magnetic relaxation, which is beyond the scope of the conventional Glaubers's Ising model and anisotropic Heisenberg model.
PubMed: 36771182
DOI: 10.3390/molecules28031516 -
International Journal of Molecular... Jan 2023Humans exploit heavy metals for various industrial and economic reasons. Although some heavy metals are essential for normal physiology, others such as Tellurium (Te),...
Humans exploit heavy metals for various industrial and economic reasons. Although some heavy metals are essential for normal physiology, others such as Tellurium (Te), Thallium (TI), antimony (Sb), and Osmium (Os) are highly toxic and can lead to Polycystic Ovarian Syndrome (PCOS), a common female factor of infertility. The current study was undertaken to determine levels of the heavy metals TI, Te, Sb and Os in serum of PCOS females ( = 50) compared to healthy non-PCOS controls ( = 56), and to relate such levels with Total Antioxidant Capacity (TAC), activity of key antioxidant enzymes, oxidative stress marker levels and redox status. PCOS serum samples demonstrated significantly higher levels of TI, Te, Sb and Os and diminished TAC compared to control ( < 0.001). Furthermore, there was significant inhibition of SOD, CAT and several glutathione-related enzyme activities in sera of PCOS patients with concurrent elevations in superoxide anions, hydrogen and lipid peroxides, and protein carbonyls, along with disrupted glutathione homeostasis compared to those of controls ( < 0.001 for all parameters). Additionally, a significant negative correlation was found between the elevated levels of heavy metals and TAC, indicative of the role of metal-induced oxidative stress as a prominent phenomenon associated with the pathophysiology of the underlying PCOS. Data obtained in the study suggest toxic metals as risk factors causing PCOS, and thus protective measures should be considered to minimize exposure to prevent such reproductive anomalies.
Topics: Humans; Female; Antioxidants; Polycystic Ovary Syndrome; Antimony; Tellurium; Thallium; Osmium; Oxidative Stress; Metals, Heavy; Oxidation-Reduction; Glutathione
PubMed: 36768916
DOI: 10.3390/ijms24032596 -
Laboratory Investigation; a Journal of... Jan 2023Immunohistochemical analysis of formalin-fixed paraffin-embedded (FFPE) tissue blocks is routinely used to identify virus-infected cells. However, detecting virus...
Immunohistochemical analysis of formalin-fixed paraffin-embedded (FFPE) tissue blocks is routinely used to identify virus-infected cells. However, detecting virus particles in FFPE sections using light microscopy is difficult because of the light diffraction resolution limitations of an optical microscope. In this study, light microscopy and field emission scanning electron microscopy were performed to observe 3-dimensional virus particles in FFPE sections in a nondestructive manner using NanoSuit or osmium conductive treatment methods. The virus particles in FFPE sections were immunostained with specific antibodies against the surface antigens of the viral particles and stained with 3,3'-diaminobenzidine. A metal solution (0.2% gold chloride or 2% osmium tetroxide) was applied to enhance the 3,3'-diaminobenzidine-stained area. This procedure is nondestructive for FFPE sections and is a simpler method than transmission electron microscopy. To validate the applicability of this technique, we performed 3-dimensional imaging of the virus particles of different sizes, such as human papillomavirus, cytomegalovirus, and varicella-zoster virus. Furthermore, ultrathin sections from the FFPE sections that were observed to harbor viral particles using field emission scanning electron microscopy were prepared and assessed using transmission electron microscopy. In the correlative areas, transmission electron microscopy confirmed the presence of large numbers of virus particles. These results indicated that the combination of marking viral particles with 3,3'-diaminobenzidine/metal staining and conductive treatment can identify active progeny virus particles in FFPE sections using scanning electron microscopy. This easy correlative imaging of field emission scanning electron microscopy of the identical area of FFPE in light microscopy may help elucidate new pathological mechanisms of virus-related diseases.
Topics: Humans; Microscopy, Electron, Scanning; Paraffin Embedding; 3,3'-Diaminobenzidine; Formaldehyde; Virion
PubMed: 36748195
DOI: 10.1016/j.labinv.2022.100020 -
RSC Chemical Biology Jan 2023Dysregulation of mitochondrial calcium uptake mediated by the mitochondrial calcium uniporter (MCU) is implicated in several pathophysiological conditions. Dinuclear...
Dysregulation of mitochondrial calcium uptake mediated by the mitochondrial calcium uniporter (MCU) is implicated in several pathophysiological conditions. Dinuclear ruthenium complexes are effective inhibitors of the MCU and have been leveraged as both tools to study mitochondrial calcium dynamics and potential therapeutic agents. In this study, we report the synthesis and characterization of Os245 ([Os(μ-N)(NH)Cl]) which is the osmium-containing analogue of our previously reported ruthenium-based inhibitor Ru265. This complex and its aqua-capped analogue Os245' ([Os(μ-N)(NH)(OH)]) are both effective inhibitors of the MCU in permeabilized and intact cells. In comparison to the ruthenium-based inhibitor Ru265 ( = 4.92 × 10 s), the axial ligand exchange kinetics of Os245 are two orders of magnitude slower ( = 1.63 × 10 s) at 37 °C. The MCU-inhibitory properties of Os245 and Os245' are different (Os245 IC for MCU inhibition = 103 nM; Os245' IC for MCU inhibition = 2.3 nM), indicating that the axial ligands play an important role in their interactions with this channel. We further show that inhibition of the MCU by these complexes protects primary cortical neurons against lethal oxygen-glucose deprivation. When administered to mice (10 mg kg), Os245 and Os245' induce seizure-like behaviors in a manner similar to the ruthenium-based inhibitors. However, the onset of these seizures is delayed, a possible consequence of the slower ligand substitution kinetics for these osmium complexes. These findings support previous studies that demonstrate inhibition of the MCU is a promising therapeutic strategy for the treatment of ischemic stroke, but also highlight the need for improved drug delivery strategies to mitigate the pro-convulsant effects of this class of complexes before they can be implemented as therapeutic agents. Furthermore, the slower ligand substitution kinetics of the osmium analogues may afford new strategies for the development and modification of this class of MCU inhibitors.
PubMed: 36685255
DOI: 10.1039/d2cb00189f -
Cancers Jan 2023Hydrodynamic transfection (HT) or hydrodynamic tail vein injection (HTVi) is among the leading technique that is used to deliver plasmid genes mainly into the liver of...
Hydrodynamic transfection (HT) or hydrodynamic tail vein injection (HTVi) is among the leading technique that is used to deliver plasmid genes mainly into the liver of live mice or rats. The DNA constructs are composed of coupled plasmids, while one contains the gene of interest that stably integrate into the hepatocyte genome with help of the other consisting sleeping beauty transposase system. The rapid injection of a large volume of DNA-solution through the tail vein induces an acute cardiac congestion that refluxed into the liver, mainly in acinus zone 3, also found through our EM study. Although, HT mediated hydrodynamic force can permeabilizes the fenestrated sinusoidal endothelium of liver, but the mechanism of plasmid incorporation into the hepatocytes remains unclear. Therefore, in the present study, we have hydrodynamically injected 2 mL volume of empty plasmid (transposon vector) or saline solution (control) into the tail vein of anesthetized C57BL/6J/129Sv mice. Liver tissue was resected at different time points from two animal group conditions, i.e., one time point per animal (1, 5, 10-20, 60 min or 24 and 48 hrs after HT) or multiple time points per animal (0, 1, 2, 5, 10, 20 min) and quickly fixed with buffered 4% osmium tetroxide. The tissues fed with only saline solution was also resected and fixed in the similar way. EM evaluation from the liver ultrathin sections reveals that swiftly after 1 min, the hepatocytes near to the central venule in the acinus zone 3 shows cytoplasmic membrane-bound vesicles. Such vesicles increased in both numbers and size to vacuoles and precisely often found in the proximity to the nucleus. Further, EM affirm these vacuoles are also optically empty and do not contain any electron dense material. Although, some of the other hepatocytes reveals sign of cell damage including swollen mitochondria, dilated endoplasmic reticulum, Golgi apparatus and disrupted plasma membrane, but most of the hepatocytes appeared normal. The ultrastructural findings in the mice injected with empty vector or saline injected control mice were similar. Therefore, we have interpreted the vacuole formation as nonspecific endocytosis without specific interactions at the plasma membrane.
PubMed: 36672277
DOI: 10.3390/cancers15020328 -
Mineralium Deposita 2023The abundance and types of reef-bearing carbonate platforms reflect the evolution of Devonian climate, with conspicuous microbial-algal reefs in the warm Early and Late...
UNLABELLED
The abundance and types of reef-bearing carbonate platforms reflect the evolution of Devonian climate, with conspicuous microbial-algal reefs in the warm Early and Late Devonian and sponge-coral reefs in the cooler Middle Devonian. A dolomitized Wenlock-Lower Devonian microbial-algal reef-bearing carbonate platform hosts epigenetic copper-cobalt-germanium (Cu-Co-Ge) sulfide mineralization at Ruby Creek-Bornite in the Brooks Range, Alaska. Here, we present rhenium-osmium (Re-Os) radiometric ages and molybdenum and sulfur (δMo = +2.04 to +5.48‰ and δS = -28.5 to -1.8‰) isotope variations for individual Cu-Co-Fe sulfide phases along the paragenetic sequence carrollite-bornite-pyrite. In the context of a hot, extensional passive margin, greenhouse conditions in the Early Devonian favored restriction of platform-top seawater circulation and episodic reflux of oxidized brines during growth of the carbonaceous carbonate platform. Molybdenum and sulfur isotope data signal the stepwise reduction of hot brines carrying Cu during latent reflux and geothermal circulation for at least ca. 15 million years from the Early Devonian until Cu-Co sulfide mineralization ca. 379-378 million years ago (Ma) in the Frasnian, Late Devonian (weighted mean of Re-Os model ages of carrollite at 379 ± 15 Ma [ = 4]; Re-Os isochron age of bornite at 378 ± 15 Ma [ = 6]). On the basis of petrographic relationships between sulfides and solid bitumen, and the Mo and S isotope data for sulfides, we imply that the endowment in critical metals (e.g., Co, Ge, Re) in the Ruby Creek-Bornite deposit is linked to the activity of primary producers that removed trace metals from the warm Early Devonian seawater and concentrated Co, Ge, and Re in algal-bacterial organic matter in carbonate sediments.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s00126-022-01123-1.
PubMed: 36644759
DOI: 10.1007/s00126-022-01123-1 -
Chemical Science Dec 2022By combining the energy input from two red photons, chemical reactions that would normally require blue or ultraviolet irradiation become accessible. Key advantages of...
By combining the energy input from two red photons, chemical reactions that would normally require blue or ultraviolet irradiation become accessible. Key advantages of this biphotonic excitation strategy are that red light usually penetrates deeper into complex reaction mixtures and causes less photo-damage than direct illumination in the blue or ultraviolet. Here, we demonstrate that the primary light-absorber of a dual photocatalytic system comprised of a transition metal-based photosensitizer and an organic co-catalyst can completely alter the reaction outcome. Photochemical reductions are achieved with a copper(i) complex in the presence of a sacrificial electron donor, whereas oxidative substrate activation occurs with an osmium(ii) photosensitizer. Based on time-resolved laser spectroscopy, this changeover in photochemical reactivity is due to different underlying biphotonic mechanisms. Following triplet energy transfer from the osmium(ii) photosensitizer to 9,10-dicyanoanthracene (DCA) and subsequent triplet-triplet annihilation upconversion, the fluorescent singlet excited state of DCA triggers oxidative substrate activation, which initiates the to isomerization of an olefin, a [2 + 2] cycloaddition, an aryl ether to ester rearrangement, and a Newman-Kwart rearrangement. This oxidative substrate activation stands in contrast to the reactivity with a copper(i) photosensitizer, where photoinduced electron transfer generates the DCA radical anion, which upon further excitation triggers reductive dehalogenations and detosylations. Our study provides the proof-of-concept for controlling the outcome of a red-light driven biphotonic reaction by altering the photosensitizer, and this seems relevant in the greater context of tailoring photochemical reactivities.
PubMed: 36605743
DOI: 10.1039/d2sc05229f -
Photochemistry and Photobiology Mar 2023Nanoformulation of an osmium photosensitizer within liposomes and micelles is used to improve the water-solubility of this highly lipophilic molecule. This highlight...
Nanoformulation of an osmium photosensitizer within liposomes and micelles is used to improve the water-solubility of this highly lipophilic molecule. This highlight report describes a recent paper by Cameron, Obaid and McFarland on this topic and discusses the context for this report. Nanoformulation has been explored as a strategy before, but this represents the first usage of this strategy with highly potent metal-based photosensitizers having phototherapeutic indices (PIs) in excess of 10 . The nanoformulation strategy is effective due to reducing aggregation and self-quenching of the photosensitizer molecules.
Topics: Liposomes; Micelles; Photosensitizing Agents; Osmium; Reproducibility of Results; Photochemotherapy
PubMed: 36588328
DOI: 10.1111/php.13776