Depolymerisation of the Klebsiella pneumoniae Capsular Polysaccharide K21 by Klebsiella Phage K5.

Klebsiella pneumoniae is a pathogen associated with various infection types, which often exhibits multiple antibiotic resistance. Phages, or bacterial viruses, have an ability to specifically target and destroy K. pneumoniae, offering a potential means of combatting multidrug-resistant infections. Phage enzymes are another promising therapeutic agent that can break down bacterial capsular polysaccharide, which shields K. pneumoniae from the immune response and external factors. In this study, Klebsiella phage K5 was isolated; this phage is active against Klebsiella pneumoniae with the capsular type K21. It was demonstrated that the phage can effectively lyse the host culture. The adsorption apparatus of the phage has revealed two receptor-binding proteins (RBPs) with predicted polysaccharide depolymerising activity. A recombinant form of both RBPs was obtained and experiments showed that one of them depolymerised the capsular polysaccharide K21. The structure of this polysaccharide and its degradation fragments were analysed. The second receptor-binding protein showed no activity on capsular polysaccharide of any of the 31 capsule types tested, so the substrate for this enzyme remains to be determined in the future. Klebsiella phage K5 may be considered a useful agent against Klebsiella infections.

Sn and Ge Complexes with Redox-Active Ligands as Efficient Interfacial Membrane-like Buffer Layers for p-i-n Perovskite Solar Cells.

Inverted perovskite solar cells with a p-i-n configuration have attracted considerable attention from the research community because of their simple design, insignificant hysteresis, improved operational stability, and low-temperature fabrication technology. However, this type of device is still lagging behind the classical n-i-p perovskite solar cells in terms of its power conversion efficiency. The performance of p-i-n perovskite solar cells can be increased using appropriate charge transport and buffer interlayers inserted between the main electron transport layer and top metal electrode. In this study, we addressed this challenge by designing a series of tin and germanium coordination complexes with redox-active ligands as promising interlayers for perovskite solar cells. The obtained compounds were characterized by X-ray single-crystal diffraction and/or NMR spectroscopy, and their optical and electrochemical properties were thoroughly studied. The efficiency of perovskite solar cells was improved from a reference value of 16.4% to 18.0-18.6%, using optimized interlayers of the tin complexes with salicylimine (1) or 2,3-dihydroxynaphthalene (2) ligands, and the germanium complex with the 2,3-dihydroxyphenazine ligand (4). The IR s-SNOM mapping revealed that the best-performing interlayers form uniform and pinhole-free coatings atop the PC61BM electron-transport layer, which improves the charge extraction to the top metal electrode. The obtained results feature the potential of using tin and germanium complexes as prospective materials for improving the performance of perovskite solar cells.

The Novel Gallium Aminobisphenolate Initiator of the Ring-Opening Copolymerization of L-Lactide and ε-Caprolactone: A Computational Study.

Density functional theory (DFT) simulations of ring-opening copolymerization of ε-caprolactone (CL) and L-lactide (LA) in presence of novel gallium complex on aminobis (phenolate) ligand are conducted. The initial steps of polymerization of CL and LA as well as the first steps of propagation which led to LGa-LA-LA-OMe, LGa-LA-CL-OMe, LGa-CL-LA-OMe, or LGa-CL-CL-OMe derivatives have been analyzed in detail. According to these data, the studied catalyst is a rare example of a catalyst in which, during copolymerization, the polymerization of CL should proceed faster than LA. Thus, we predict the formation of a mainly block copolymer poly(CL-block-LA) using this catalyst.

Gallium (III) Complexes Based on Aminobisphenolate Ligands: Extremely High Active ROP-Initiators from Well-Known and Easily Accessible Compounds.

We report herein the synthesis and full characterizations of the first examples of gallium complexes based on "privileged" aminobisphenolate ligands which are easily available. These complexes turned out to be extremely active in the ring-opening polymerization of ε-caprolactone even at room temperature and highly active in the ROP of L-lactide. The combination of factors such as the easy availability of these compounds and the supposedly low toxicity, together with the extremely high activity in ROP, allows us to consider these compounds as suitable for use on an industrial scale for the synthesis of biodegradable polymers for biomedical applications.

2-Imidazoline Nitroxide Derivatives of Cymantrene.

The 2-imidazoline nitroxide derivatives of cymantrene-2-(η5-cyclopentadienyl)tricarbonylmanganese(I)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (NNMn) and 2-(η5-cyclopentadienyl)tricarbonylmanganese(I)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-1-oxyl (INMn) were synthesized. It was shown that NNMn and INMn exhibit a sufficiently high kinetic stability both in solids and in solutions under normal conditions. Their structural characteristics, magnetic properties and electrochemical behavior are close to Re(I) analogs. This opens the prospect of using paramagnetic cymantrenes as prototypes in the design of Re(I) half-sandwiched derivatives for theranostics, where therapy is combined with diagnostics by magnetic resonance imaging due to the contrast properties of nitroxide radicals.

Remote Stereoelectronic Effects in Pyrrolidone- and Caprolactam-Substituted Phenols: Discrepancies in Antioxidant Properties Evaluated by Electrochemical Oxidation and H-Atom Transfer Reactivity.

New antioxidants are commonly evaluated via two main approaches, i.e., the ability to donate an electron and the ability to intercept free radicals. We compared these approaches by evaluating the properties of 11 compounds containing both antioxidant moieties (mono- and polyphenols) and auxiliary pharmacophores (pyrrolidone and caprolactam). Several common antioxidants, such as butylated hydroxytoluene (BHT), 2,3,5-trimethylphenol (TMP), quercetin, and dihydroquercetin, were added for comparison. The antioxidant properties of these compounds were determined by their rates of reaction with 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and their oxidation potentials from cyclic voltammetry. Although these methods test different chemical properties, their results correlate reasonably well. However, several exceptions exist where the two methods give opposite predictions! One of them is the different behavior of mono- and polyphenols: polyphenols can react with DPPH more than an order of magnitude faster than monophenols of a similar oxidation potential. The second exception stems from the size of a "bystander" lactam ring at the benzylic position. Although the phenols with a seven-membered lactam ring are harder to oxidize, the sterically nonhindered compounds react with DPPH about 2× faster than the analogous five-membered lactams. The limitations of computational methods, especially those based on a single parameter, are also evaluated and discussed.

Investigations into the structure-activity relationship in gemini QACs based on biphenyl and oxydiphenyl linker.

Eighteen novel gemini quaternary ammonium compounds were synthesized to examine the effect of linker nature, aliphatic chain length and their relative position on antibacterial and antifungal activity. The synthesized compounds showed strong bacteriostatic activity against a panel of both Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and two fungi. Some of these compounds exhibited a wider and more potent antimicrobial spectrum than commonly-used antiseptics, such as benzalkonium chloride (BAC), cetylpyridinium chloride (CPC), chlorhexidine digluconate (CHG) and octenidine dihydrochloride (OCT).

Supramolecular D⋯A-layered structures based on germanium complexes with 2,3-dihydroxynaphthalene and N,N'-bidentate ligands.

The concept of using redox-active ligands, which has become extremely widespread in organometallic chemistry, is often considered from 'their effect on the metal center properties' point of view and 'how to modify the ligands'. In this paper, we present the reverse side of this effective approach - a dramatic change of redox properties of ligands under the influence of a redox-inert metal. Germanium derivatives based on 2,3-dihydroxynaphthalene (1) and N,N'-bidentate ligands, namely 2,2'-bipyridine (2) and 1,10-phenanthroline (3), were obtained and characterized by CV, UV-vis spectroscopy, DFT calculations and in the case of 3 X-ray diffraction. It was shown that the HOMO of the complexes is almost completely located on the naphthalene fragment while the LUMO is on the N,N-ligands. At the same time, there are no boundary molecular orbitals on the germanium atom, but it forms the axial part of the molecule holding two opposite motifs together. Moreover, it sharply affects the level of HOMO and LUMO. Derivatives 2 and 3 are more easily oxidized compared to 2,3-dihydroxynaphthalene by 0.31-0.34 V (7-8 kcal mol-1) and are more easily reduced compared to N,N-donors by 1.08-1.15 V (25-26.5 kcal mol-1). All this together makes it possible to form a system with a narrow HOMO/LUMO gap (∼2 eV). The crystal structure of 3 consists of alternating monomolecular easily oxidizing and easily reducing layers formed due to intermolecular interactions, in particular π-stacking. In addition, in contrast to 1 that starts to decompose noticeably at the temperatures from 200 °C, 2 and 3 have an extremely high thermal stability. They remain stable with no signs of decomposition and melting up to 400 °Ð¡. We believe that this approach to the formation of the supramolecular structure may present prospects for obtaining new functional materials.

Re(i)-nitroxide complexes.

Spin-labeled cyrhetrenes [(NNCp)Re(CO)3] and [(INCp)Re(CO)3], where NNCp is nitronyl nitroxide 2-(η5-cyclopentadienyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl and INCp is the corresponding imino nitroxide, were synthesized and characterized by EPR, CV, XRD, magnetochemistry and quantum chemistry methods. The correlations between different arrangements of paramagnetic centers and the magnetic exchange interactions for three polymorphs of [(NNCp)Re(CO)3] were studied. It was concluded that high kinetic stability of nitroxide-substituted cyrhetrenes is a promising feature of compounds for the creation of multifunctional contrast agents.

Catalyst-Solvent System for PASE Approach to Hydroxyquinolinone-Substituted Chromeno[2,3-b]pyridines Its Quantum Chemical Study and Investigation of Reaction Mechanism.

The Pot, Atom, and Step Economy (PASE) approach is based on the Pot economy principle and unites it with the Atom and Step Economy strategies; it ensures high efficiency, simplicity and low waste formation. The PASE approach is widely used in multicomponent chemistry. This approach was adopted for the synthesis of previously unknown hydroxyquinolinone substituted chromeno[2,3-b]pyridines via reaction of salicylaldehydes, malononitrile dimer and hydroxyquinolinone. It was shown that an ethanol-pyridine combination is more beneficial than other inorganic or organic catalysts. Quantum chemical studies showed that chromeno[2,3-b]pyridines has potential for corrosion inhibition. Real time 1H NMR monitoring was used for the investigation of reaction mechanism and 2-((2H-chromen-3-yl)methylene)malononitrile was defined as a key intermediate in the reaction.

2-Carboxyethylgermanium Sesquioxide as A Promising Anode Material for Li-Ion Batteries.

Various forms of germanium and germanium-containing compounds and materials are actively investigated as energy-intensive alternatives to graphite as the anode of lithium-ion batteries. The most accessible form-germanium dioxide-has the structure of a 3D polymer, which accounts for its rapid destruction during cycling, and requires the development of further approaches to the production of nanomaterials and various composites based on it. For the first time, we propose here the strategy of using 2-carboxyethylgermanium sesquioxide ([O1.5 GeCH2 CH2 CO2 H]n , 2-CEGS), in lieu of GeO2 , as a promising, energy-intensive, and stable new source system for building lithium-ion anodes. Due to the presence of the organic substituent, the formed polymer has a 1D or a 2D space organization, which facilitates the reversible penetration of lithium into its structure. 2-CEGS is common and commercially available, completely safe and non-toxic, insoluble in organic solvents (which is important for battery use) but soluble in water (which is convenient for manufacturing diverse materials from it). This paper reports the preparation of micro- (flower-shaped agglomerates of ≈1 µm thick plates) and nanoformed (needle-shaped nanoparticles of ≈500×(50-80) nm) 2-CEGS using methods commonly available in laboratories and industry such as vacuum and freeze-drying of aqueous solutions of 2-CEGS. Lithium half-cell anodes based on 2-CEGS show a capacity of ≈400 mAh g-1 for microforms and up to ≈700 mAh g-1 for nanoforms, which is almost two times higher than the maximal theoretical capacity of graphite. These anodes are stable during the cycling at various rates. The results of DFT simulations suggest that Li atoms form the stable Li2 O with the oxygen atoms of 2-CEGS, and actual charge-discharge cycles involve deoxygenated GeC3 H5 molecules. Thus, C3 chains loosen the anode structure compared to pure Ge, improving its ability to accommodate Li ions.

Pot, atom and step economic (PASE) assembly of salicylaldehydes, malononitrile dimer and 4-hydroxypyridine-2(1H)-ones into medicinally relevant 5H-chromeno[2,3-b]pyridine scaffold.

The new multicomponent reaction (MCR) has been found: one-pot selective and efficient formation of the new 5-(4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl)-substituted 5H-chromeno[2,3-b]pyridines in 61-97% yields directly from simple and easily available salicylaldehydes, malononitrile dimer and 4-hydroxypyridine-2(1H)-ones in small amount of pyridine-ethanol catalyst/solvent system. This complex "domino" transformation includes Knoevenagel condensation of salicylaldehyde with malononitrile dimer, Michael addition of 4-hydroxypyridine-2(1H)-one, double Pinner-type reaction cyclization and isomerization with following protonation. This facile multicomponent process opens a new way to 5-(4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl)-substituted 5H-chromeno[2,3-b]pyridine systems, which are promising compounds for the treatment for human inflammatory TNFα-mediated diseases and different biomedical applications.

One-pot five-component high diastereoselective synthesis of polysubstituted 2-piperidinones from aromatic aldehydes, nitriles, dialkyl malonates and ammonium acetate.

A novel five-component diastereoselective synthesis of polysubstituted 2-piperidinones is reported. The Knoevenagel condensation-Michael addition-Mannich cascade of two equivalents of aromatic aldehydes, nitriles, dialkyl malonates and ammonium acetate or aqueous ammonia in alcohols provides convenient access to alkyl (3SR,4RS,6SR)-5,5-dicyano-2-oxo-4,6-diarylpiperidine-3-carboxylates with three stereocenters in 52-90% or dialkyl (2SR,3RS,4RS,5SR)-2,4-diaryl-3-cyano-6-oxopiperidine-3,5-dicarboxylates with four stereocenters in 38-88%. The formation of products was highly stereoselective, with only one diastereomer formed. Ammonium acetate or aqueous ammonia plays a role both as a catalyst and as a nitrogen source. 2,4,6-triaryl-3,3,5,5-tetracyanopiperidines were obtained as a side products in the reactions with nitro-substituted aldehydes or with ethyl and n-propyl cyanoacetates. A series of 14 2-piperidinones and piperidines was assessed for antimicrobial activity against a panel of five bacteria and two fungi; no significant activity was observed. Two side piperidines with nitro substituents in aromatic ring possess bacteriostatic action against S. aureus ATCC 43300 and A. baumannii ATCC 19606 at 32 ug/mL.

Infrared-Spectroscopic Study of (4-Methylpent-3-en-1-ynyl)methylthiocarbene, Its Photochemical Transformations, and Reactions in an Argon Matrix.

The first representative of singlet carbenes bearing both ethynyl and methylthio groups at the carbene center, (4-methylpent-3-en-1-ynyl)methylthiocarbene, has been generated in a low-temperature Ar matrix upon UV photolysis of 3,3-dimethyl-5-methylthioethynyl-3H-pyrazole and detected by FTIR spectroscopy. The generation of the carbene proceeds via intermediate (3-diazo-5-methylhex-4-en-1-ynyl)methylsulfane. The comparison of FTIR spectroscopy data with the results of quantum chemical calculations (B3LYP/aug-cc-pVTZ) and NRT analysis shows that (4-methylpent-3-en-1-ynyl)methylthiocarbene has a singlet ground state with the localization of the unpaired spins on the carbon atom in the α-position to methylthio moiety. Two major pathways of further phototransformation of the studied carbene have been found. One of them produces photochemically stable thioketone (S═CMe-C≡C-CH═CMe2) as a result of methyl group migration from sulfur to the neighboring carbon atom, and the other one leads to the formation of labile thioketene (S═C═C(Me)-CH═CH-CMe═CH2). Ability of (4-methylpent-3-en-1-ynyl)methylthiocarbene to insert into the H-Cl bond was established, which additionally confirms the singlet nature of this intermediate.

Novel non-toxic high efficient antibacterial azido chitosan derivatives with potential application in food coatings.

In this work, we developed a simple method for the preparation of N-(3-azido-2-hydroxypropyl)chitosan. We compared the antibacterial activity of N-(3-azido-2-hydroxypropyl)chitosans and previously synthesized N-(2-azidoethyl)chitosans. N-(3-azido-2-hydroxypropyl)chitosans possess higher antibacterial effect which is comparable with that of ampicillin and gentamicin. The effect is due to azido pharmacophore -CH2-CH(OH)-CH2-N3 (for N-(3-azido-2-hydroxypropyl)chitosan) or -CH2-CH2-N3 (for N-(2-azidoethyl)chitosan) introduced in chitosan chain, since the corresponding organic azides NH2-CH2-CH2-N3 and NH2-CH2-CH2-N3 are characterized by high antibacterial activity. However, high antibacterial organic azides NH2-CH2-CH2-N3 and NH2-CH2-CH2-N3 are characterized by high toxicity. Their conjugation to the chitosan chain saves their antibacterial effect, but strongly diminishes their toxicity, and the toxicity of the resulting derivatives is comparable with that of the starting chitosan. These findings are of interest to food science, since novel effective food coatings can be developed on basis of prepared derivatives.

Identification of CDC42 Effectors Operating in FGD1-Dependent Trafficking at the Golgi.

Loss of function mutations in the FGD1 gene cause a rare X-linked disease, faciogenital dysplasia (FGDY, also known as Aarskog-Skott syndrome), which is associated with bone and urogenital abnormalities. The FGD1 gene encodes à CDC42-specific guanine nucleotide exchange factor. The mutations are frequently located in the DH module of FGD1 preventing its transformation to the active form. We previously reported that Golgi-associated FGD1 regulates post-Golgi transport of some conventional and bone-specific proteins in a CDC42-dependent manner. However, the downstream targets of FGD1/CDC42 signaling that operate to support transport from the Golgi remain elusive. Here, we demonstrate that Golgi-localized CDC42 effectors might be involved in FGD1-mediated post-Golgi transport, probably through coordination of Golgi membrane and cytoskeleton dynamics. Overexpression of effector-specific CDC42 mutants (exhibiting preferential affinities for PAK1, IQGAP1, N-WASP, or PAR6) only partially rescue membrane trafficking in FGD1-deficient cells, indicating that the orchestrated activities of several downstream targets of CDC42 are required to support FGD1-mediated export from the Golgi. Our findings provide new insights into understanding the molecular mechanisms behind FGD1/CDC42-dependent transport events and uncover new targets whose potential might be explored for correction of membrane trafficking in FGDY.

Upconversion of Reductants.

The many applications of photon upconversion-conversion of low-energy photons into high-energy photons-raises the question of the possibility of "electron upconversion". In this Review, we illustrate how the reduction potential can be increased by using the free energy of exergonic chemical reactions. Electron (reductant) upconversion can produce up to 20-25 kcal mol-1 of additional redox potential, thus creating powerful reductants under mild conditions. We will present the two common types of electron-upconverting systems-dissociative (based on unimolecular fragmentations) and associative (based on the bimolecular formation of three-electron bonds). The possible utility of reductant upconversion encompasses redox chain reactions in electrocatalytic processes, photoredox cascades, design of peroxide-based medicines, firefly luminescence, and reductive repair of DNA photodamage.

Halogen-free GeO2 conversion: electrochemical reduction vs. complexation in (DTBC)2Ge[Py(CN)n] (n = 0 2) complexes.

3,5-di-tert-Butylcatecholate (DTBC) germanium complexes (DTBC)2Ge[Py(CN)n]2 (n = 0…2) have been synthesized from GeO2, 3,5-di-tert-butylcatechol and cyano-substituted pyridines Py(CN)n and characterized by elemental analysis, NMR, IR and UV-VIS spectroscopy. The structure of 1 (with 4-cyanopyridine) has been determined by X-ray single crystal analysis. UV-VIS spectra have shown that these complexes are stable in CH3CN, toluene and CH2Cl2 solutions; in contrast, they are rapidly decomposed by dimethylformamide and tetrahydrofuran. Complexes 1 and 2 (with 4-cyano and 3-cyanopyridine) are electrochemically reducible in toluene/1 M Bu4NPF6 at E = -1.3…-1.7 V vs. AgCl. The quantum-chemical study of these complexes is in accordance with the unsuccessful attempts to obtain analogous derivatives with 2-cyanopyridine and 2,6-dicyanopyridine.

High diastereoselective amine-catalyzed Knoevenagel-Michael-cyclization-ring-opening cascade between aldehydes, 3-arylisoxazol-5(4H)-ones and 3-aminocyclohex-2-en-1-ones.

A highly diastereoselective three-component cascade reaction among aromatic aldehydes, 3-arylisoxazol-5(4H)-ones and 3-aminocyclohex-2-en-1-ones takes place under the catalysis of triethylamine, providing (3SR,4SR)-4-aryl-3-[(E)-(hydroxyimino)(aryl)methyl]-4,6,7,8-tetrahydroquinoline-2,5(1H,3H)-diones in 45-85% yields. The transformation presumably proceeds through a sequential cascade of Knoevenagel/Michael-addition/cyclization/ring-opening reactions. This process was carried out in green media (EtOH/water, 1:1-1:3) at reflux. Products are crystallized directly from the reaction mixture and their isolation includes only filtration. The structure of (3SR,4SR)-3-[(E)-(hydroxyimino)(phenyl)methyl]-7,7-dimethyl-4-phenyl-4,6,7,8-tetrahydroquinoline-2,5(1H,3H)-dione was confirmed by X-ray diffraction analysis.

Correction: Subcellular Partitioning of Protein Tyrosine Phosphatase 1B to the Endoplasmic Reticulum and Mitochondria Depends Sensitively on the Composition of Its Tail Anchor.

[This corrects the article DOI: 10.1371/journal.pone.0139429.].