Homochiral Ketals in Organic Synthesis. Enantioselective Synthesis of (4S, 5S)-4,5-Dihydroxycyclopent-2-En-1-One Isopropylidine Ketal

The title compound has been synthesized in 17% yield over six steps from 2-cyclopenten-1-one. The key step is catalytic osmylation of 4-bromo-2-cyclopenten-1-one 1,4-di-O-benzyl-D-threitol ketal to produce a chromatographically separable mixture of diastereomeric diols.     

Facile and convenient synthesis of aryl hydrazines via copper-catalyzed C–N cross-coupling of aryl halides and hydrazine hydrate

An efficient and convenient method for the synthesis of aryl hydrazines has been developed via copper-catalyzed cross-coupling of aryl bromides and hydrazine with a readily accessible ligand and water as a solvent. The multigram scale procedure is applicable to aryl bromides bearing both moderately electron-donating and electron-withdrawing substituents in the aromatic nucleus. No column chromatography is required to obtain aryl hydrazine hydrochlorides in good yields.     

Characterization of hydromedusan Ca2+-regulated photoproteins as a tool for measurement of Ca2+concentration

Calcium ion is a ubiquitous intracellular messenger, performing this function in many eukaryotic cells. To understand calcium regulation mechanisms and how disturbances of these mechanisms are associated with disease states, it is necessary to measure calcium inside cells. Ca²⁺-regulated photoproteins have been successfully used for this purpose for many years. Here we report the results of comparative studies on the properties of recombinant aequorin from Aequorea victoria, recombinant obelins from Obelia geniculata and Obelia longissima, recombinant mitrocomin from Mitrocoma cellularia, and recombinant clytin from Clytia gregaria as intracellular calcium indicators in a set of identical in vitro and in vivo experiments. Although photoproteins reveal a high degree of identity of amino acid sequences and spatial structures, and, apparently, have a common mechanism for the bioluminescence reaction, they were found to differ in the Ca²⁺ concentration detection limit, the sensitivity of bioluminescence to Mg²⁺, and the rates of the rise of the luminescence signal with a sudden change of Ca²⁺ concentration. In addition, the bioluminescence activities of Chinese hamster ovary cells expressing wild-type photoproteins also differed. The light signals of cells expressing mitrocomin, for example, slightly exceeded the background, suggesting that mitrocomin may be hardly used to detect intracellular Ca²⁺ without modifications improving its properties. On the basis of experiments on the activation of endogenous P2Y₂ receptor in Chinese hamster ovary cells by ATP, we suggest that wild-type aequorin and obelin from O. longissima are more suitable for calcium detection in cytoplasm, whereas clytin and obelin from O. geniculata can be used for calcium measurement in cell compartments with high Ca²⁺ concentration. Figure

Hydromedusan photoproteins differ in Ca²⁺ concentration detection limit, sensitivity of bioluminescence to Mg²⁺, and rates of rise of luminescence signal with a sudden change of [Ca²⁺] despite a high degree of identity of their amino acid sequences and spatial structures, and, apparently, a common mechanism for the bioluminescence reaction.     

Enumeration of non-labile oxygen atoms in dissolved organic matter by use of 16O/18O exchange and Fourier transform ion-cyclotron resonance mass spectrometry

We report a simple approach for enumeration of non-labile oxygen atoms in individual molecules of dissolved organic matter (DOM), using acid-catalyzed ¹⁶O/¹⁸O exchange and ultrahigh-resolution Fourier-transform ion-cyclotron-resonance mass spectrometry (FTICR-MS). We found that by dissolving DOM in H₂ ¹⁸O at 95 °C for 20 days it is possible to replace all oxygen atoms of DOM molecules (excluding oxygen from ether groups) with ¹⁸O. The number of exchanges in each molecule can be determined using high-resolution FTICR. Using the proposed method we identified the number of non-labile oxygen atoms in 231 molecules composing DOM. Also, using a previously developed hydrogen–deuterium (H/D)-exchange approach we identified the number of labile hydrogen atoms in 450 individual molecular formulas. In addition, we observed that several backbone hydrogen atoms can be exchanged for deuterium under acidic conditions. The method can be used for structural and chemical characterization of individual DOM molecules, comparing different DOM samples, and investigation of biological pathways of DOM in the environment.     

xMAP-based analysis of three most prevalent staphylococcal toxins in Staphylococcus aureus cultures

Detection of staphylococcal toxins presents a great interest for medical diagnostics. Screening of clinical samples for the presence of several types of staphylococcal toxins using traditional methods—biological tests on animals or cell cultures as well as ELISA—is laborious. Multiplex detection methods would simplify testing. We have designed an xMAP-based assay to detect three staphylococcal toxins—enterotoxins A and B (SEA and SEB) and toxic shock syndrome toxin (TSST)—in cultural supernatants obtained from different strains of Staphylococcus aureus. The limits of detection of SEA, SEB, and TSST multiplex detection in S. aureus growth medium were 10, 1,000, and 5 pg/mL, respectively. Fifty-nine samples of S. aureus cultural supernatants were tested with the xMAP assay. The developed assay has proved highly effective detection of the natural toxins in the samples obtained due to bacterial cells cultivation. In prospect, the developed test system can be used in clinical diagnostics and in monitoring of foodstuffs and environmental objects.     

Computational Insights into the Catalytic Mechanism of Is-PETase: An Enzyme Capable of Degrading Poly(ethylene) Terephthalate

Is-PETase has become an enzyme of significant interest due to its ability to catalyse the degradation of polyethylene terephthalate (PET) at mesophilic temperatures. We performed hybrid quantum mechanics and molecular mechanics (QM/MM) at the DSD-PBEP86-D3/ma-def2-TZVP/CHARMM27//rev-PBE-D3/dev2-SVP/CHARMM level to calculate the energy profile for the degradation of a suitable PET model by this enzyme. Very low overall barriers are computed for serine protease-type hydrolysis steps (as low as 34.1 kJ mol⁻¹). Spontaneous deprotonation of the final product, terephthalic acid, with a high computed driving force indicates that product release could be rate limiting.     

Development of Magnesium Anode-Based Transient Primary Batteries

Biodegradable primary batteries, also known as transient batteries, are essential to realize autonomous biodegradable electronic devices with high performance and advanced functionality. In this work, magnesium, copper, iron, and zinc – metals that exist as trace elements in the human body – were tested as materials for biomedical transient electronic devices. Different full cell combinations of Mg and X (where X = Cu, Fe, and Zn and the anodized form of the metals) with phosphate buffered saline (PBS) as electrolyte were studied. To form the cathodes, metal foils were anodized galvanostatically at a current density of 2.0 mA cm⁻² for 30 mins. Electrochemical measurements were then conducted for each electrode combination to evaluate full cell battery performance. Results showed that the Mg−Cu_anodized chemistry has the highest power density at 0.99 mW/cm². Nominal operating voltages of 1.26 V for the first 0.50 h and 0.63 V for the next 3.7 h were observed for Mg−Cu_anodized which was discharged at a current density of 0.70 mA cm⁻². Among the materials tested, Mg−Cu_anodized exhibited the best discharge performance with an average specific capacity of 2.94 mAh cm⁻², which is comparable to previous reports on transient batteries.     

Are bosonic replicas faulty?

Motivated by the ongoing discussion about a seeming asymmetry in the performance of fermionic and bosonic replicas, we present an exact, nonperturbative approach to both fermionic and bosonic zero-dimensional replica field theories belonging to the broadly interpreted beta=2 Dyson symmetry class. We then utilize the formalism developed to demonstrate that the bosonic replicas do correctly reproduce the microscopic spectral density in the QCD-inspired chiral Gaussian unitary ensemble. This disproves the myth that the bosonic replica field theories are intrinsically faulty.     

Multivalent Recognition of Concanavalin A by {Mo132} Glyconanocapsules—Toward Biomimetic Hybrid Multilayers

Herein, we consider Müller’s spherical, porous, anionic, molybdenum oxide based capsule, (NH₄)₄₂‐ [{(Mo^VI)Mo^VI₅O₂₁(H₂O)₆}₁₂{Mo^V₂O₄(CH₃COO)}₃₀]?10 CH₃COONH₄? 300 H₂O≡(NH₄)₄₂? 1 a ?crystal ingredients≡ 1 , {Mo₁₃₂}, as an effective sugar‐decorated nanoplatform for multivalent lectin recognition. The ion‐exchange of NH₄⁺ ions of 1 with cationic‐sugars, D ‐mannose‐ammonium chloride ( 2 ) or D ‐glucose‐ammonium chloride ( 3 ) results in the formation of glyconanocapsules (NH₄)_42?n 2 _n? 1 a and (NH₄)_42?m 3 _m? 1 a . The Mannose (NH₄)_42?n 2 _n? 1 a capsules bind selectively Concanavalin A (Con A) in aqueous solution, giving an association avidity constant of ${K{{{\rm multi}\hfill \atop {\rm a}\hfill}}}$ =4.6×10⁴ M ^?1 and an enhancement factor of β=K${{{{\rm multi}\hfill \atop {\rm a}\hfill}}}$ /K${{{{\rm mono}\hfill \atop {\rm ass}\hfill}}}$ =21.9, reminiscent of the formation of “glycoside clusters” on the external surface of glyconanocapsule. The glyconanocapsules (NH₄)_42?n 2 _n? 1 a and (NH₄)_42?m 3 _m? 1 a self‐assemble in “hybrid multilayers” by successive layer‐by‐layer deposition of (NH₄)_42?n 2 _n? 1 a or (NH₄)_42?m 3 _m? 1 a and Con A. These architectures, reminiscent of versatile mimics of artificial tissues, can be easily prepared and quantified by using quartz crystal microgravimetry (QCM). The “biomimetic hybrid multilayers” described here are stable under a continual water flow and they may serve as artificial networks for a greater depth of understanding of various biological mechanisms, which can directly benefit the fields of chemical separations, sensors or storage‐delivery devices.     

PET Imaging of Bacterial Infections with Fluorine‐18‐Labeled Maltohexaose

A positron emission tomography (PET) tracer composed of ¹⁸F‐labeled maltohexaose (MH¹⁸F) can image bacteria in vivo with a sensitivity and specificity that are orders of magnitude higher than those of fluorodeoxyglucose (¹⁸FDG). MH¹⁸F can detect early‐stage infections composed of as few as 10⁵ E. coli colony‐forming units (CFUs), and can identify drug resistance in bacteria in vivo. MH¹⁸F has the potential to improve the diagnosis of bacterial infections given its unique combination of high specificity and sensitivity for bacteria.