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Journal of the American Society For... Mar 2020The Os arene anticancer complex [(η-bip)Os(en)Cl] (Os1-Cl; where bip = biphenyl and en = ethylenediamine) binds strongly to DNA and biomolecules. Here we investigate...
The Os arene anticancer complex [(η-bip)Os(en)Cl] (Os1-Cl; where bip = biphenyl and en = ethylenediamine) binds strongly to DNA and biomolecules. Here we investigate the interaction between Os1-Cl and the model protein, BSA, using ultrahigh resolution Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS). The specific binding location of Os1 on BSA was investigated with the use of collisionally activated dissociation (CAD) and electron capture dissociation (ECD). CAD MS/MS was found to dissociate the osmium complex from the metallo-peptide complex readily producing unmodified fragments and losing location information. ECD MS/MS, however, successfully retains the osmium modification on the peptides upon fragmentation allowing localization of metallocomplex binding. This study reveals that lysine is a possible binding location for Os1-Cl, apart from the expected binding sites at methionine, histidine, and cysteine. Using a nano liquid chromatography (nLC)-FT-ICR ECD MS/MS study, multiple binding locations, including the N-terminus and C-terminus of digested peptides, glutamic acid, and lysine were also revealed. These results show the multitargeting binding ability of the organo-osmium compound and can be used as a standard workflow for more complex systems, e.g., metallocomplex-cell MS analysis, to evaluate their behavior toward commonly encountered biomolecules.
Topics: Amino Acid Sequence; Animals; Antineoplastic Agents; Binding Sites; Cattle; Coordination Complexes; Models, Molecular; Osmium; Peptides; Protein Binding; Serum Albumin, Bovine; Tandem Mass Spectrometry
PubMed: 31967804
DOI: 10.1021/jasms.9b00054 -
Analytical Methods : Advancing Methods... Aug 2020Electrochemical sensors are used by millions of patients and health care providers every year, yet these measurements are hindered by compounds that also exhibit...
Electrochemical sensors are used by millions of patients and health care providers every year, yet these measurements are hindered by compounds that also exhibit inherent redox activity. Acetaminophen (APAP) is one such interferent that falls into this extensive class. In this work, an osmium-based redox polymer was used for electrochemical detection in a sensor that was operated at a decreased voltage, allowing for decreased interference. These sensors demonstrated better selectivity (40-fold for glucose and 200-fold for lactate) for their respective analyte over APAP, possessed higher sensitivity (0.350 ± 0.006 μA mM for glucose and 2.00 ± 0.05 μA mM for lactate) over a broad range of analyte concentrations (50 μM-10 mM for glucose and 2-324 μM for lactate), and displayed similar operational stability (26% decrease for glucose and 29% decrease for lactate) over 7 days compared to first-generation sensors. To test this platform under biologically-relevant conditions, glucose metabolism was monitored in a model liver cell line, Alpha Mouse Liver 12 (AML12) after treatment with APAP and/or insulin. This work represents a high-resolution electrochemical biosensor for microphysiological monitoring of glucose and lactate in the presence of APAP.
Topics: Acetaminophen; Animals; Biosensing Techniques; Glucose; Humans; Lactic Acid; Mice; Oxidation-Reduction
PubMed: 32789376
DOI: 10.1039/d0ay00528b -
Metallomics : Integrated Biometal... Apr 2021The treatment of tuberculosis (TB) poses a major challenge as frontline therapeutic agents become increasingly ineffective with the emergence and spread of...
The treatment of tuberculosis (TB) poses a major challenge as frontline therapeutic agents become increasingly ineffective with the emergence and spread of drug-resistant strains of Mycobacterium tuberculosis (Mtb). To combat this global health problem, new antitubercular agents with novel modes of action are needed. We have screened a close family of 17 organometallic half-sandwich Os(II) complexes [(arene)Os(phenyl-azo/imino-pyridine)(Cl/I)]+Y- containing various arenes (p-cymene, biphenyl, or terphenyl), and NMe2, F, Cl, or Br phenyl or pyridyl substituents, for activity towards Mtb in comparison with normal human lung cells (MRC5). In general, complexes with a monodentate iodido ligand were more potent than chlorido complexes, and the five most potent iodido complexes (MIC 1.25-2.5 µM) have an electron-donating Me2N or OH substituent on the phenyl ring. As expected, the counter anion Y (PF6-, Cl-, I-) had little effect on the activity. The pattern of potency of the complexes towards Mtb is similar to that towards human cells, perhaps because in both cases intracellular thiols are likely to be involved in their activation and their redox mechanism of action. The most active complex against Mtb is the p-cymene Os(II) NMe2-phenyl-azopyridine iodido complex (2), a relatively inert complex that also exhibits potent activity towards cancer cells. The uptake of Os from complex 2 by Mtb is rapid and peaks after 6 h, with temperature-dependence studies suggesting a major role for active transport. Significance to Metallomics Antimicrobial resistance is a global health problem. New advances are urgently needed in the discovery of new antibiotics with novel mechanisms of action. Half-sandwich organometallic complexes offer a versatile platform for drug design. We show that with an appropriate choice of the arene, an N,N-chelated ligand, and monodentate ligand, half-sandwich organo-osmium(II) complexes can exhibit potent activity towards Mycobacterium tuberculosis (Mtb), the leading cause of death from a single infectious agent. The patterns of activity of the 17 azo- and imino-pyridine complexes studied here towards Mtb and normal lung cells suggest a common redox mechanism of action involving intracellular thiols.
Topics: Antineoplastic Agents; Antitubercular Agents; Cell Proliferation; Humans; Molecular Structure; Mycobacterium tuberculosis; Neoplasms; Organometallic Compounds; Osmium; Tuberculosis; Tumor Cells, Cultured
PubMed: 33693931
DOI: 10.1093/mtomcs/mfab007 -
Journal of the American Chemical Society Dec 2022Aryl amination is an essential transformation for medicinal, process, and materials chemistry. In addition to classic Buchwald-Hartwig amination conditions,...
Aryl amination is an essential transformation for medicinal, process, and materials chemistry. In addition to classic Buchwald-Hartwig amination conditions, blue-light-driven metallaphotoredox catalysis has emerged as a valuable tool for C-N cross-coupling. However, blue light suffers from low penetration through reaction media, limiting its scalability for industrial purposes. In addition, blue light enhances unwanted side-product formation in metallaphotoredox catalysis, namely hydrodehalogenation. Low-energy light, such as deep red (DR) or near-infrared (NIR), offers a solution to this problem as it can provide enhanced penetration through reaction media as compared to higher-energy wavelengths. Herein, we show that low-energy light can also enhance the desired reactivity in metallaphotoredox catalysis by suppressing unwanted hydrodehalogenation. We hypothesize that the reduced side product is formed by direct photolysis of the aryl-nickel bond by the high-energy light, leading to the generation of aryl radicals. Using deep-red or near-infrared light and an osmium photocatalyst, we demonstrate an enhanced scope of (hetero)aryl bromides and amine-based nucleophiles with minimal formation of hydrodehalogenation byproducts.
Topics: Catalysis; Amination; Light; Nickel; Bromides
PubMed: 36417474
DOI: 10.1021/jacs.2c09745 -
Biosensors & Bioelectronics Oct 2023Viruses have unique coat proteins that are genetically modifiable. Their surface can serve as a nano-template on which electroactive molecules are immobilized. In this...
Viruses have unique coat proteins that are genetically modifiable. Their surface can serve as a nano-template on which electroactive molecules are immobilized. In this study, we report filamentous bacteriophage as a backbone to which redox mediators are covalently and densely tethered, constructing redox nanowire, i.e. an electron conducting biomaterial. The highly ordered coat proteins of a filamentous bacteriophage provide flexible and biocompatible platform to constitute a biohybrid redox nanowire. Incorporating bacteriophage and redox molecules form an entangled assembly of nanowires enabling facile electron transfer. Electron transfer among the molecular mediators in the entangled assembly originates apparent electron diffusion of which the electron transfer rate is comparable to that observed in conventional redox polymers. Programming peptide terminals suggests further enhancement in electron mediation by increasing redox species mobility. In addition, the redox nanowire film functions as a favorable matrix for enzyme encapsulation. The stability of the enzymes entrapped in this unique matrix is substantially improved.
Topics: Nanowires; Biosensing Techniques; Oxidation-Reduction; Electron Transport; Bacteriophages; Electrodes
PubMed: 37442029
DOI: 10.1016/j.bios.2023.115518 -
Materials (Basel, Switzerland) Jun 2022Lead sludge from copper production is a source of rare metals, such as rhenium and osmium, whose content reaches 0.06-0.08% and 0.0025-0.0050%, respectively. The base of...
Lead sludge from copper production is a source of rare metals, such as rhenium and osmium, whose content reaches 0.06-0.08% and 0.0025-0.0050%, respectively. The base of the sludge consists of lead sulfate. A method of reductive smelting of lead sludge from copper smelting production at 1000-1100 °C has been developed. Coke was used as a reducing agent and sodium sulfate as a slag-forming material. Optimal conditions for selective extraction of rare metals in smelting products were found: osmium in the form of metallic form into raw lead and rhenium in the form of perrhenate compound NaReO into sodium-sulfate slag. The developed technology makes it possible to extract rhenium with a high degree of extraction in the form of water-soluble compounds for the subsequent production of commercial salts of rhenium by the known hydrometallurgical methods. The content of rhenium in the slag phase is 0.18-0.25%, with its initial content in the slime of 0.06-0.08%. The degree of rhenium concentration at the first stage of processing is 3-3.2 times in the form of water-soluble perrhenate. Osmium and lead do not form solid solutions; osmium in crude lead is mainly concentrated in the lower zones of lead. A method of obtaining a concentrate containing 53-67% osmium from raw lead with an initial content of 0.0025-0.0050% in the slurry and a concentration number of 13,000-21,000 times has been proposed.
PubMed: 35744129
DOI: 10.3390/ma15124071 -
Microscopy Research and Technique Apr 2021Lobomycosis is a skin infection produced by the fungus Lacazia loboi, which mainly affects some indigenous and afro-descendant populations in Tropical America. We...
Lobomycosis is a skin infection produced by the fungus Lacazia loboi, which mainly affects some indigenous and afro-descendant populations in Tropical America. We previously reported the comparative effect of osmium tetroxide (OsO ) and ruthenium tetroxide (RuO ) in the electron microscopy (EM) of other related microorganisms. The objective of this study is to compare the effect of postfixation with OsO and RuO in the ultrastructure of L. loboi yeasts. Skin biopsies on patients diagnosed with lobomycosis were fixed in glutaraldehyde at 3% and postfixed in the following solutions: (a) 1% OsO , (b) 0.2% RuO , and (c) OsO at 1% followed by RuO at 0.2%. They were then processed using the conventional method for EM. Unlike OsO the treatment with RuO revealed different shades of gray and electron dense bands in the cell wall and other cell components of L. loboi. The most notable finding was the presence of radial filamentous structures around the yeast, which made the image look like the sun. Postfixation with RuO revealed ultrastructural details that had not been previously reported for L loboi. The combined use of OsO and RuO in EM of microorganisms with cell walls can be useful to evaluate the effect of microbicide substances.
Topics: Humans; Lacazia; Microscopy, Electron; Osmium Tetroxide; Ruthenium Compounds
PubMed: 33176034
DOI: 10.1002/jemt.23638 -
Inorganic Chemistry Aug 2021Metal-coordination-driven C-C bond functionalization without involvement of the traditional route of oxidative addition, insertion, and reductive elimination has gained...
Metal-coordination-driven C-C bond functionalization without involvement of the traditional route of oxidative addition, insertion, and reductive elimination has gained immense importance. In this context, the present Communication highlights the facile ring contraction process of the deprotonated bis-lawsone (L) to functionalized L1 upon coordination to {Os(bpy)} or isomeric {Os(pap)} (bpy = 2,2'-bipyridine and pap = 2-phenylazopyridine) in -. Further, recognition of fractional redox noninnocence of L1 in - via experimental and theoretical events facilitated its inclusion in the redox noninnocent family.
PubMed: 34310111
DOI: 10.1021/acs.inorgchem.1c01680 -
Journal of Enzyme Inhibition and... Dec 2022A novel automated method based on sequential injection analysis (SIA), a non-segmented flow injection technique, was developed to evaluate glutathione S-transferase P1-1...
A novel automated method based on sequential injection analysis (SIA), a non-segmented flow injection technique, was developed to evaluate glutathione S-transferase P1-1 (GST P1-1) activity in the presence of organometallic complexes with putative anticancer activity. The assay is based on the reaction of L-glutathione (GSH) and 1-chloro-2,4-dinitrobenzene (CDNB) in the presence of GST P1-1 to afford the GS-DNB conjugate and the reaction may be monitored by an increase in absorbance at 340 nm. A series of ruthenium, iron, osmium and iridium complexes were evaluated as GST P1-1 inhibitors by evaluating their half-maximal inhibitory concentration (IC). An iridium compound displays the lowest IC value of 6.7 ± 0.7 µM and an iron compound displays the highest IC value of 275 ± 9 µM. The SIA method is simple to use, robust, reliable, and efficient and uses fewer reagents than batch methods and each analysis takes only 5 minutes.
Topics: Glutathione; Glutathione S-Transferase pi; Glutathione Transferase; Iridium; Organometallic Compounds
PubMed: 35635138
DOI: 10.1080/14756366.2022.2073443 -
Scientific Reports Oct 2022Characterization of brain infarct lesions in rodent models of stroke is crucial to assess stroke pathophysiology and therapy outcome. Until recently, the analysis of...
Characterization of brain infarct lesions in rodent models of stroke is crucial to assess stroke pathophysiology and therapy outcome. Until recently, the analysis of brain lesions was performed using two techniques: (1) histological methods, such as TTC (Triphenyltetrazolium chloride), a time-consuming and inaccurate process; or (2) MRI imaging, a faster, 3D imaging method, that comes at a high cost. In the last decade, high-resolution micro-CT for 3D sample analysis turned into a simple, fast, and cheaper solution. Here, we successfully describe the application of brain contrasting agents (Osmium tetroxide and inorganic iodine) for high-resolution micro-CT imaging for fine location and quantification of ischemic lesion and edema in mouse preclinical stroke models. We used the intraluminal transient MCAO (Middle Cerebral Artery Occlusion) mouse stroke model to identify and quantify ischemic lesion and edema, and segment core and penumbra regions at different time points after ischemia, by manual and automatic methods. In the transient-ischemic-attack (TIA) mouse model, we can quantify striatal myelinated fibers degeneration. Of note, whole brain 3D reconstructions allow brain atlas co-registration, to identify the affected brain areas, and correlate them with functional impairment. This methodology proves to be a breakthrough in the field, by providing a precise and detailed assessment of stroke outcomes in preclinical animal studies.
Topics: Animals; Mice; Osmium Tetroxide; X-Ray Microtomography; Stroke; Infarction, Middle Cerebral Artery; Disease Models, Animal; Iodine
PubMed: 36261475
DOI: 10.1038/s41598-022-21494-9