Mucin-Triggered Osmium Nanoclusters as Protein-Corona-Like Nanozymes with Photothermal-Enhanced Peroxidase-Like Activity for Tumor-Specific Therapy.

Nanomaterials with peroxidase-like activity and photothermal conversion efficiency have garnered significant attention for their ability to generate cytotoxic hydroxyl radicals and provide synergistic therapeutic effects. Selecting nanozymes with suitable properties and carriers is crucial for maximizing efficacy. While the mucin family is known for its mucoadhesive, glycosylated structures that enhance drug bioavailability and targeting, its potential in nanozymes remains underexplored. Here, we utilize mucin-2 to facilitate osmium nanoclusters (Os@Mucin), creating protein-corona-like nanozymes. This configuration bestows Os@Mucin with excellent peroxidase-like activity (769 U/mg) and photothermal conversion efficiency (22.83%, 808 nm). Mucin-2 promotes Os uptake by cells, allowing Os@Mucin to exhibit tumor environment-responsive peroxidase-like activity, further enhanced under photothermal conditions for targeted cytotoxicity and synergistic effects. In vivo experiments demonstrate that this integration effectively treats triple-negative breast cancer. This study innovatively highlights the potential of the mucin family and underscores the promising role of Os nanozymes in tumor therapy.

Ab initio multireference calculation of electronic spectra of the osmium complexes, [Os(bpy) 3 ] 2 + and [Os(phen) 3 ] 2 + .

The spin-orbit coupling corrected absorption spectra of osmium complexes, [Os(bpy) 3 ] 2 + and [Os(phen) 3 ] 2 + , were calculated by using ab initio multireference perturbation method (NEVPT2) with relativistic effects taken into account throughout ZORA approximation and corresponding all-electron basis sets. For the same purpose, the time-dependent DFT techniques were used. A very good agreement between NEVPT2 and experimental spectra should be highlighted, especially for the MLCT transitions that occur in visible and near-UV regions ( 16 , 000 - 33 , 000 cm - 1 ). Moreover, the present study offers description of excited states of titled osmium complexes and their spectra interpretation using molecular orbitals.

OsO2 as the Contrast-Generating Chemical Species of Osmium-Stained Biological Tissues in Electron Microscopy.

Electron imaging of biological samples stained with heavy metals has enabled visualization of subcellular structures critical in chemical-, structural-, and neuro-biology. In particular, osmium tetroxide (OsO4) has been widely adopted for selective lipid imaging. Despite the ubiquity of its use, the osmium speciation in lipid membranes and the process for contrast generation in electron microscopy (EM) have continued to be open questions, limiting efforts to improve staining protocols and therefore high-resolution nanoscale imaging of biological samples. Following our recent success using photoemission electron microscopy (PEEM) to image mouse brain tissues with synaptic resolution, we have used PEEM to determine the nanoscale electronic structure of Os-stained biological samples. Os(IV), in the form of OsO2, generates nanoaggregates in lipid membranes, leading to a strong spatial variation in the electronic structure and electron density of states. OsO2 has a metallic electronic structure that drastically increases the electron density of states near the Fermi level. Depositing metallic OsO2 in lipid membranes allows for strongly enhanced EM signals and conductivity of biological materials. The identification of the chemical species and understanding of the membrane contrast mechanism of Os-stained biological specimens provides a new opportunity for the development of staining protocols for high-resolution, high-contrast EM imaging.

In-cell Catalysis by Tethered Organo-Osmium Complexes Generates Selectivity for Breast Cancer Cells.

Anticancer agents that exhibit catalytic mechanisms of action offer a unique multi-targeting strategy to overcome drug resistance. Nonetheless, many in-cell catalysts in development are hindered by deactivation by endogenous nucleophiles. We have synthesised a highly potent, stable Os-based 16-electron half-sandwich ('piano stool') catalyst by introducing a permanent covalent tether between the arene and chelated diamine ligand. This catalyst exhibits antiproliferative activity comparable to the clinical drug cisplatin towards triple-negative breast cancer cells and can overcome tamoxifen resistance. Speciation experiments revealed Os to be almost exclusively albumin-bound in the extracellular medium, while cellular accumulation studies identified an energy-dependent, protein-mediated Os accumulation pathway, consistent with albumin-mediated uptake. Importantly, the tethered Os complex was active for in-cell transfer hydrogenation catalysis, initiated by co-administration of a non-toxic dose of sodium formate as a source of hydride, indicating that the Os catalyst is delivered to the cytosol of cancer cells intact. The mechanism of action involves the generation of reactive oxygen species (ROS), thus exploiting the inherent redox vulnerability of cancer cells, accompanied by selectivity for cancerous cells over non-tumorigenic cells.

A brief history of the Feulgen reaction.

One hundred years ago, Robert Feulgen published a landmark paper in which he described the first method to stain DNA in cells and tissues. Although a century has passed since the discovery by Feulgen and Rossenbeck, the chemical reaction still exerts an important influence in current histochemical studies. Its contribution in diverse fields, spanning from biomedicine to plant biology, has paved the way for the most significant studies that constitute our current knowledge. The possibility to specifically explore the DNA in cell nuclei while quantifying its content makes it a contemporary and timeless method. Indeed, many histocytochemical studies following the 1924 paper have led to a deep understanding of genome organization in general as well as several specific mechanisms (e.g. DNA duplication or tumour pathology) that, nowadays, constitute some of the most fundamental pillars in biological investigations. In this review, we discuss the chemistry and application of the Feulgen reaction to both light and electron microscopy.

Facile Method to Obtain Functionalised η6-Bound Arenes in Ru(II) and Os(II) Half-Sandwich Complexes.

Half-sandwich Ru(II)- and Os(II)-arene complexes have great potential for catalytic and biological applications. The possibility of fine-tuning their chemical reactivity by including modifications in the ligands around the metal adds to their many advantages. However, structural modifications at the η6-bound arene have had significant synthetic limitations, particularly in the design of Os(II)-tethered complexes. For the first time, we have employed a practical C(sp3)-C(sp2) coupling to obtain 28 new Ru(II) and Os(II) η6-arene half-sandwich complexes with a wide variety of arene functionalities, including those that enable the formation of tether rings, such as quinoline, and coumarin. The introduction of novel functional groups at the arene in Ru(II)- and Os(II) half-sandwich complexes can broaden the synthetic scope of this type of organometallic complexes, and help to take full advantage of their structural diversity, for example, in intracellular catalysis.

Synthesis and Spectroscopic Study of a Homogenous Bimetallic Os(II) Complex as a New Gastric Cancer Photosensitizer.

A homogenous dinuclear Os(II) complex bisOs was synthesized and fully characterized. The electrochemical cyclic voltammetry study, and density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations were performed to investigate the electronic property. bisOs showed an obvious interaction with lipase and BSA, and can generate singlet oxygen under blue and red LED light irradiation, with a singlet oxygen quantum yield (ΦΔ) of 0.36 in comparison to that of [Ru(bpy)3]Cl2 in acetonitrile. bisOs exhibited moderate to great photocytotoxicity against HGC-27 human gastric cancer cells under blue LED light irradiation, giving the IC50 value as low as 1.83 µM (PI value is 9.7), while was almost non-cytotoxic in the dark. The cellular singlet oxygen detection in HGC-27 cancer cells exhibited a concentration-dependent manner, and cell uptake of bisOs in A549 cells was as high as 120 ng/106 cells, subcellular colocalization study indicated that bisOs was not accumulated in nucleus, and less likely to target mitochondria. This work provides a new example of dinuclear osmium complex as potential photosensitizer candidate for gastric treatment.

Laminarin-modulated osmium nanozymes with high substrate-affinity and selective peroxidase-like behavior engineered colorimetric assay for hydroxyl radical scavenging capacity estimation.

Hydroxyl radical (·OH) scavenging capacity (HOSC) estimation is essential for evaluating antioxidants, natural extracts, or drugs against clinical diseases. While nanozymes offer advantages in related applications, they still face limitations in activity and selectivity. In response, this work showcases the fabrication of laminarin-modulated osmium (laminarin-Os) nanoclusters (1.45 ± 0.05 nm), functioning as peroxidase-like nanozymes within a colorimetric assay tailored for rational HOSC estimation. This study validates both the characterization and remarkable stability of laminarin-Os. By leveraging the abundant surface negative charges of laminarin-Os and the surface hydroxyls of laminarin, oxidation reactions are facilitated, augmenting laminarin-Os's affinity for 3,3',5,5'-tetramethylbenzidine (TMB) (KM = 0.04 mM). This enables the laminarin-Os-based colorimetric assay to respond to ·OH more effectively than citrate-, albumin-, or other polysaccharides-based Os. In addition, experimental results also validate the selective peroxidase-like behavior of laminarin-Os under acidic conditions. Antioxidants like ascorbic acid, glutathione, tannic acid, and cysteine inhibit absorbance at 652 nm in the colorimetric platform using laminarin-Os's peroxidase-like activity. Compared with commercial kits, this assay demonstrates superior sensitivity (e.g., responds to ascorbic acid 0.01-0.075 mM, glutathione 1-15 µg/mL, tannic acid 0.5-5 µM, and monoammonium glycyrrhizinate cysteine 1.06-10.63 µM) and HOSC testing for glutathione, tannic acid, and monoammonium glycyrrhizinate cysteine. Overall, this study introduces a novel Os nanozyme with exceptional TMB affinity and ·OH selectivity, paving the way for HOSC estimation in biomedical research, pharmaceutical analysis, drug quality control, and beyond.

Emulsion Liquid Membranes Based on Os-NP/n-Decanol or n-Dodecanol Nanodispersions for p-Nitrophenol Reduction.

Membrane materials with osmium nanoparticles have been recently reported for bulk membranes and supported composite membrane systems. In the present paper, a catalytic material based on osmium dispersed in n-decanol (nD) or n-dodecanol (nDD) is presented, which also works as an emulsion membrane. The hydrogenation of p-nitrophenol (PNP) is carried out in a reaction and separation column in which an emulsion in the acid-receiving phase is dispersed in an osmium nanodispersion in n-alcohols. The variables of the PNP conversion process and p-aminophenol (PAP) transport are as follows: the nature of the membrane alcohol, the flow regime, the pH difference between the source and receiving phases and the number of operating cycles. The conversion results are in all cases better for nD than nDD. The counter-current flow regime is superior to the co-current flow. Increasing the pH difference between the source and receiving phases amplifies the process. The number of operating cycles is limited to five, after which the regeneration of the membrane dispersion is required. The apparent catalytic rate constant (kapp) of the new catalytic material based on the emulsion membrane with the nanodispersion of osmium nanoparticles (0.1 × 10-3 s-1 for n-dodecanol and 0.9 × 10-3 s-1 for n-decanol) is lower by an order of magnitude compared to those based on adsorption on catalysts from the platinum metal group. The advantage of the tested membrane catalytic material is that it extracts p-aminophenol in the acid-receiving phase.

Chemotherapeutic Activities of New η6-p-Cymene Ruthenium(II) and Osmium(II) Complexes with Chelating SS and Tridentate SNS Ligands.

A series of new chelating bidentate (SS) alkylimidazole-2-thione-Ru(II)/Os(II) complexes (3ai, 3aii, 3aiii, 3bii/4aiii, 4bi, 4bii), and the tridentate (SNS) pyridine-2,6-diylimidazole-2-thione-Ru(II)/Os(II) complexes (5bi, 5civ/6bi, 6ci, 6civ) in the forms [MII(cym)(L)Cl]PF6 and [MII(cym)(L)]PF6 (M = Ru or Os, cym = η6-p-cymene, and L = heterocyclic derivatives of thiourea) respectively, were successfully synthesized. Spectroscopic and analytical methods were used to characterize the complexes and their ligands. Solid-state single-crystal X-ray diffraction analyses revealed a "piano-stool" geometry around the Ru(II) or Os(II) centers in the respective complexes. The complexes were investigated for in vitro chemotherapeutic activities against human cervical carcinoma (HeLa) and the non-cancerous cell line (Hek293) using the MTT assay. The compounds 3aii, 5civ, 5bi, 4aiii, 6ci, 6civ, and the reference drug, 5-fluorouracil were found to be selective toward the tumor cells; the compounds 3ai, 3aiii, 3bii, 4bi, 4bii, and 6bi, which were found not to be selective between normal and tumor cell lines. The IC50 value of the tridentate half-sandwich complex 5bi (86 ± 9 µM) showed comparable anti-proliferative activity with the referenced commercial anti-cancer drug, 5-fluorouracil (87 ± 15 µM). The pincer (SNS) osmium complexes 6ci (36 ± 10 µM) and 6civ (40 ± 4 µM) were twice as effective as the reference drug 5-fluorouracil at the respective dose concentrations. However, the analogous pincer (SNS) ruthenium complex 5civ was ineffective and did not show anti-proliferative activity, even at a higher concentration of 147 ± 1 µM. These findings imply that the higher stability of the chelating (SS) and the pincer (SNS) ligand architectures in the complexes improves the biological (anti-proliferative) activity of the complexes by reducing the chance of ligand dissociation under physiological conditions. In general, the pincer (SNS) osmium complexes were found to be more cytotoxic than their ruthenium analogues, suggesting that the anti-proliferative activity of the imidazole-2-thione-Ru/Os complexes depends on the ligand's spatial coordination, the nature of the metal center, and the charge of the metal complex ions.

Photocatalytic CO2 Reduction Using an Osmium Complex as a Panchromatic Self-Photosensitized Catalyst: Utilization of Blue, Green, and Red Light.

The photocatalytic reduction of carbon dioxide (CO2) represents an attractive approach for solar-energy storage and leads to the production of renewable fuels and valuable chemicals. Although some osmium (Os) photosensitizers absorb long wavelengths in the visible-light region, a self-photosensitized, mononuclear Os catalyst for red-light-driven CO2 reduction has not yet been exploited. Here, we discovered that the introduction of an Os metal to a PNNP-type tetradentate ligand resulted in the absorption of light with longer-wavelength (350-700 nm) and that can be applied to a panchromatic self-photosensitized catalyst for CO2 reduction to give mainly carbon monoxide (CO) with a total turnover number (TON) of 625 under photoirradiation (λ≥400 nm). CO2 photoreduction also proceeded under irradiation with blue (λ0=405 nm), green (λ0=525 nm), or red (λ0=630 nm) light to give CO with >90 % selectivity. The quantum efficiency using red light was determined to be 12 % for the generation of CO. A catalytic mechanism is proposed based on the detection of intermediates using various spectroscopic techniques, including transient absorption, electron paramagnetic resonance, and UV/Vis spectroscopy.

Targeting cancer lactate metabolism with synergistic combinations of synthetic catalysts and monocarboxylate transporter inhibitors.

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.

Cyclization, Decyclization, and Metallacyclization of Pyridine-Substituted Homopropargylic Alcohols on Ruthenium(II) and Osmium(II) Centers.

Systematic investigations on the reactions between cis-[M(dppm)2 Cl2 ] (M=Ru/Os; dppm=1,1-bis(diphenylphosphino)methane) and pyridine/quinoline substituted homopropargylic alcohols uncovered the diverse Ru(II)/Os(II)-induced alkyne activation pathways. The alkynes underwent cyclization on M via a "non-vinylidene" pathway at lower temperatures, resulting in alkenyl intermediates which might further metallacyclize to give metallapyrroloindolizines. Conversely, reactions at higher temperatures induced alkyne cyclization on M via a "vinylidene" pathway, affording cyclic oxacarbene complexes. Additionally, a rare decyclization mechanism was observed during the transformation of a metallacyclization-resistant alkenyl complex into a cyclic oxacarbene complex. DFT calculations were employed to validate the experimental findings. Overall, these results not only provide insights into controlling alkyne activation pathways, but also offer new strategies for preparing metalated heterocyclic and metallacyclic complexes.

G-Quadruplex Binding of an NIR Emitting Osmium Polypyridyl Probe Revealed by Solution NMR and Time-Resolved Infrared Studies.

G-quadruplexes are emerging targets in cancer research and understanding how diagnostic probes bind to DNA G-quadruplexes in solution is critical to the development of new molecular tools. In this study the binding of an enantiopure NIR emitting [Os(TAP)2 (dppz)]2+ complex to different G-quadruplex structures formed by human telomer (hTel) and cMYC sequences in solution is reported. The combination of NMR and time-resolved infrared spectroscopic techniques reveals the sensitivity of the emission response to subtle changes in the binding environment of the complex. Similar behaviour is also observed for the related complex [Os(TAP)2 (dppp2)]2+ upon quadruplex binding.

Metal-rich organic matter and hot continental passive margin: drivers for Devonian copper-cobalt-germanium mineralization in dolomitized reef-bearing carbonate platform.

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 (δ98/95Mo = +2.04 to +5.48‰ and δ34S = -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 [n = 4]; Re-Os isochron age of bornite at 378 ± 15 Ma [n = 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.

An Insight into the Impact of Serum Tellurium, Thallium, Osmium and Antimony on the Antioxidant/Redox Status of PCOS Patients: A Comprehensive Study.

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 (n = 50) compared to healthy non-PCOS controls (n = 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 (p < 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 (p < 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.

Interplay of Anisotropic Exchange Interactions and Single-Ion Anisotropy in Single-Chain Magnets Built from Ru/Os Cyanidometallates(III) and Mn(III) Complex.

Two novel 1D heterobimetallic compounds {[MnIII(SB2+)MIII(CN)6]·4H2O}n (SB2+ = N,N'-ethylenebis(5-trimethylammoniomethylsalicylideneiminate) based on orbitally degenerate cyanidometallates [OsIII(CN)6]3- (1) and [RuIII(CN)6]3- (2) and MnIII Schiff base complex were synthesized and characterized structurally and magnetically. Their crystal structures consist of electrically neutral, well-isolated chains composed of alternating [MIII(CN)6]3- anions and square planar [MnIII(SB2+)]3+ cations bridged by cyanide groups. These -ion magnetic anisotropy of MnIII centers. These results indicate that the presence of compounds exhibit single-chain magnet (SCM) behavior with the energy barriers of Δτ1/kB = 73 K, Δτ2/kB = 41.5 K (1) and Δτ1/kB = 51 K, Δτ2 = 27 K (2). Blocking temperatures of TB = 2.8, 2.1 K and magnetic hysteresis with coercive fields (at 1.8 K) of 8000, 1600 Oe were found for 1 and 2, 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 MIII(4d/5d)-CN-MnIII fragments: -JxSMxSMnx-JySMySMny-JzSMzSMnz, with opposite sign of exchange parameters Jx = -22, Jy = +28, Jz = -26 cm-1 and Jx = -18, Jy = +20, Jz = -18 cm-1 in 1 and 2, respectively) and single orbitally degenerate [OsIII(CN)6]3- and [RuIII(CN)6]3- spin units with unquenched orbital angular momentum in the chain compounds 1 and 2 leads to a peculiar regime of slow magnetic relaxation, which is beyond the scope of the conventional Glaubers's 1D Ising model and anisotropic Heisenberg model.

Half-Sandwich Type Platinum-Group Metal Complexes of C-Glucosaminyl Azines: Synthesis and Antineoplastic and Antimicrobial Activities.

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 C-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 O-perbenzylated 2-nitro-glucal. Reduction of the adducts and, where necessary, subsequent protecting group manipulations furnished the above C-glucosaminyl heterocycles in their O-perbenzylated, O-perbenzoylated and O-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 p-cymene and iridium complexes with Cp* had the best performance in ovarian cancer cells, followed by osmium complexes with p-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, O-benzyl groups were superior to O-benzoyl groups. The IC50 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 Staphylococcus aureus and Enterococcus clinical isolates in the low micromolar range.

Structurally Simple Osmium(II) Polypyridyl Complexes as Photosensitizers for Photodynamic Therapy in the Near Infrared.

Five osmium(II) polypyridyl complexes of the general formula [Os(4,7-diphenyl-1,10-phenanthroline)2 L]2+ were synthesized as photosensitizers for photodynamic therapy by varying the nature of the ligand L. Thanks to the pronounced π-extended structure of the ligands and the heavy atom effect provided by the osmium center, these complexes exhibit a high absorption in the near-infrared (NIR) region (up to 740 nm), unlike related ruthenium complexes. This led to a promising phototoxicity in vitro against cancer cells cultured as 2D cell layers but also in multicellular tumor spheroids upon irradiation at 740 nm. The complex [Os(4,7-diphenyl-1,10-phenanthroline)2 (2,2'-bipyridine)]2+ was found to be the most efficient against various cancer cell lines, with high phototoxicity indexes. Experiments on CT26 tumor-bearing BALB/c mice also indicate that the OsII complexes could significantly reduce tumor growth following 740 nm laser irradiation. The high phototoxicity in the biological window of this structurally simple complex makes it a promising photosensitizer for cancer treatment.

Potassium permanganate is an excellent alternative to osmium tetroxide in freeze-substitution.

High-pressure freezing followed by freeze-substitution is a valuable method for ultrastructural analyses of resin-embedded biological samples. The visualization of lipid membranes is one of the most critical aspects of any ultrastructural study and can be especially challenging in high-pressure frozen specimens. Historically, osmium tetroxide has been the preferred fixative and staining agent for lipid-containing structures in freeze-substitution solutions. However, osmium tetroxide is not only a rare and expensive material, but also volatile and toxic. Here, we introduce the use of a combination of potassium permanganate, uranyl acetate, and water in acetone as complementing reagents during the freeze-substitution process. This mix imparts an intense en bloc stain to cellular ultrastructure and membranes, which makes poststaining superfluous and is well suited for block-face imaging. Thus, potassium permanganate can effectively replace osmium tetroxide in the freeze-substitution solution without sacrificing the quality of ultrastructural preservation.