ABSTRACT
A one-pot cascade chlorination/heterocyclization strategy has been developed for the synthesis of 2,4-dichloro-substituted quinolines from acylated anilines using triphosgene and triphenylphosphine oxide. Obviating the conventional harsh conditions of chlorination, synthetic useful quinolines with moderate to good yields were obtained through this reaction. The mechanism study exhibited that the formation of a ß-enamine intermediate plays a vital role in the generation of the final product.
ABSTRACT
The stalling development of antibiotics, especially against intrinsically resistant Gram-negative pathogens associated with outer membranes, leads to an emerging antibiotic crisis across the globe. To breathe life into existing drugs, we herein report a hypoxia-responsive nanoparticle (NP) that encapsulates a hydrophobic antibiotic, rifampicin, and a cationic potentiator, polysulfonium. The simultaneous release of antibiotics and potentiators can be promoted and inhibited in response to the severity of bacterial-induced hypoxia, leading to antimicrobial dosing in a precision manner. Under the synergism of polysulfoniums with membrane-disruption capability, the NPs can intensively decrease the antibiotic dose by up to 66-95% in eliminating planktonic Gram-negative P. aeruginosa bacteria and achieve an 8-log reduction of bacteria in mature biofilms at rifampicin MIC. The NP formulation demonstrates that precision dosing of antibiotics and potentiators regulated by hypoxia provides a promising strategy to maximize efficacy and minimize toxicity in treating Gram-negative bacterial infection.
Subject(s)
Anti-Bacterial Agents , Nanoparticles , Humans , Anti-Bacterial Agents/pharmacology , Rifampin , Gram-Negative Bacteria , Drug Resistance, Microbial , Hypoxia/drug therapyABSTRACT
Polyaniline (PANI) has been studied as soft electronic materials, which is still subject to performance obstacles such as low thermal conductivity and undesirable electrical conductivity. Herein, we report thein situpreparation of an atomically thin hydroxylated boron nitride (HO-BNNS)@PANI actiniae-like layered composite. HO-BNNS@PANI composite obtains brilliant electrical and thermal conductivity without destroying the pH sensitivity of PANI. In this case, the test results show that when the HO-BNNS content is 15 wt%, the conductivity of the HO-BNNS@PANI composite is 10.8 S cm-1, and the thermal conductivity is 1.21 W m-1·K-1(≈520% that of pure PANI). More strikingly, the HO-BNNS@PANI composite maintains the pH responsiveness of the intrinsic PANI. This greatly improves the application range of composite materials. Meanwhile, since actiniae-like structural factors simultaneously improve ion diffusion capability and optimize reaction area, after five times of doping and dedoping, the conductivity of the HO-BNNS@PANI composite can still be maintained above 60%.
ABSTRACT
Sepsis is an inflammatory disease with exacerbated inflammation at early stages. Inflammatory cytokines play critical roles in the pathophysiology of sepsis. Ubiquitin-specific peptidase 18 (USP18), a deubiquitinating enzyme, has been shown to modulate transforming growth factor-ß-activated kinase 1 (TAK1) activity. However, the precise role of USP18 in sepsis is not clear. Here, we investigated the potential effect of USP18 on inflammation in sepsis. We generated mice with USP18 or/and TAK1 deficiency in macrophages (USP18MKO mice, TAK1MKO mice and USP18MKO-TAK1MKO mice) and established a lipopolysaccharide (LPS)-induced sepsis model in mice. Bone marrow-derived macrophages were isolated from wild-type (WT), USP18MKO or TAK1MKO mice and treated with LPS or CpG, and the expression of cytokines including IL-6, IL-10, IL-1ß and tumor necrosis factor α (TNF-α) was measured. The activation of NF-κB, ERK and p38 signaling pathways and ubiquitination of TAK1 were detected. We induced sepsis in WT, USP18MKO, TAK1MKO or USP18MKO-TAK1MKO mice and evaluated the survival rate, lung pathology and inflammatory cytokine levels in serum. Macrophages deficient in USP18 produced significantly increased IL-6, IL-1ß and TNF-α post-LPS or -CpG stimulation. Macrophages deficient in USP18 had promoted activation of NF-κB, p38 and ERK, and increased ubiquitination of TAK1. Mice with TAK1 deficiency in macrophages had increased survival rates, decreased immune cell infiltration in lung and decreased pro-inflammatory cytokines in serum. In contrast, mice with USP18 deficiency in macrophages had decreased survival rates, increased cell infiltration in lung and increased pro-inflammatory cytokines in serum. USP18 alleviated LPS-induced sepsis by inhibiting TAK1 activity.
Subject(s)
MAP Kinase Kinase Kinases/metabolism , Sepsis/metabolism , Ubiquitin Thiolesterase/metabolism , Animals , Cytokines/metabolism , Inflammation/metabolism , Lipopolysaccharides/pharmacology , Macrophages/metabolism , Mice , Mice, Inbred C57BL , NF-kappa B/metabolism , Sepsis/chemically induced , Signal Transduction/physiology , Tumor Necrosis Factor-alpha/metabolism , Ubiquitination/physiologyABSTRACT
Signal amplification for electrochemiluminescence (ECL) plays a significant role in ultrasensitive detection of disease biomarkers. We report herein a new signal amplification strategy-quasi-photonic crystal nanomembrane-based light scattering enhancement for ECL signal amplification, via fabricating a novel close-packed monolayered SiO2-nanomembrane as solid-state ECL electrodes. In the system, the quasi-photonic crystal structure of the monolayered SiO2-nanomembrane led to intense light scattering within the nanofilm, which significantly increases the photon flux and then definitely improves the excitation number of the luminescent molecules (Ru(bpy)32+). Reinforced by the nanostructured electrode surface of the nanomembrane, the as-prepared ECL electrode exhibited significant ECL enhancement, â¼77-fold enhancement in the classic Ru(bpy)32+-TPrA system. We further constructed a sandwich-type SiO2-nanomembrane based solid-state ECL immunobiosensor for ultrasensitive detection of cardiac troponin I (cTnI). Under optimal conditions, the immunobiosensor exhibited a very low limit of detection (LOD) of 5.6 fg mL-1 for cTnI. Due to the cheap and easy availability of the materials, this study and findings not only provide an efficient way to improve the ECL intensity but also benefit the design of novel ECL electrodes for various biomarker detections.
Subject(s)
Electrochemical Techniques/methods , Nanostructures/chemistry , Silicon Dioxide/chemistry , Troponin I/blood , Electrodes , Humans , Limit of Detection , Luminescence , Luminescent Measurements/methods , Nanostructures/ultrastructureABSTRACT
The structural, fluorescence properties and binding interaction of benzazaborole derivatives 1-hydroxy-2-(α-methyl) benzyl-1,2-benzo boron nitrogen heterocyclic-3-phosphate diethyl ester (PADE) and 1-hydroxy-2-(2-chloro) benzyl-1,2-benzo boron nitrogen heterocyclic-3-phosphate diethyl ester (PADC) with iodide ion have been investigated utilizing density functional theory (DFT) and Time-dependent density functional theory (TD-DFT) method, in which the PADE and PADC showed strong emission in aqueous solution and fluorescence quenching was observed upon addition of iodide ion. The theoretical study indicates that the strong hydrogen-bond (O-H I) between benzazaborole derivatives and iodide ion leads to the formation of the benzazaborole-iodide ion complexes. The excited state properties have been explored by theoretical calculation to understand the fluorescent quenching upon introduction of iodide ion. The strong fluorescent emission is originated by the electron transfer from benzyl and phosphate moieties to benzo boron nitrogen fused heterocycle moiety, while the fluorescence quenching is attributed to the electron transfer between the PADE (PADC) and iodide ion. The density difference (EDD) maps and the frontier molecular orbitals diagrams during excitation and de-excitation process demonstrate that the photoinduced electron transfer process between PADE (PADC) and iodide ion leads to fluorescence quenching after a significant internal conversion.
Subject(s)
Fluorescent Dyes/chemistry , Iodides/chemistry , Ions/chemistry , Models, Theoretical , Density Functional Theory , Electron Transport , Fluorescence , Hydrogen Bonding , Models, Molecular , Molecular Conformation , Molecular StructureABSTRACT
Electrochemiluminescence (ECL) has emerged as one of the most important methods for in vitro diagnosis and detection, but it is still limited in sensitivity for ultrasensitive biodetections. Fast and ultrasensitive detection of biomolecules is critical, especially for the clinical detection of cardiac troponin I (cTnI) for cardiac infarction diagnosis. In this study, an effective tactic was developed to enhance ECL efficiency of the luminol system, by combined use of Co2+-based metal organic frameworks (MOF), zeolitic imidazolate frameworks (ZIF-67), and luminol-capped Ag nanoparticles (luminol-AgNPs). The integration leads to a pronounced â¼115-fold enhancement in luminol ECL. On the basis of this fascinating sensing platform, a robust label-free ECL immunosensor was constructed for ultrasensitive detection of cTnI, the main marker of myocardial infarction, with good stability and a detection limit as low as 0.58 fg mL-1 (S/N = 3).
Subject(s)
Biosensing Techniques , Electrochemical Techniques , Luminescent Measurements , Luminol/chemistry , Metal-Organic Frameworks/chemistry , Troponin I/analysis , Biosensing Techniques/instrumentation , Cobalt/chemistry , Electrochemical Techniques/instrumentation , Humans , Luminescent Measurements/instrumentation , Metal Nanoparticles/chemistry , Particle Size , Silver/chemistry , Surface PropertiesABSTRACT
In the paper, hydrothermal carbon spheres (HTCs) are functionalized by the 3-aminobenzeneboronic acid (3-APBA) as a fluorescence sensor. The modification carbon spheres (3-APBA-HTCs) have shown excellent selectivity and sensitivity for efficient determination of L-tryptophan (L-Trp). The fluorescence sensor can selectively achieve the "On-Off" switchable functionality for L-Trp at an extremely low detection limit of 0.50 × 10- 5 mol/L.
Subject(s)
Biosensing Techniques/methods , Boronic Acids/chemistry , Carbon/chemistry , Fluorescence , Quantum Dots/chemistry , Spectrometry, Fluorescence/methods , Tryptophan/analysis , Limit of DetectionABSTRACT
4ZnO·B2O3·H2O:Ln3+ (Ln=Eu, Tb) phosphors with different morphologies have been successfully synthesized via one-step hydrothermal method through regulating the molar amount of Eu3+ and Tb3+. Comprehensive scanning electron microscopy (SEM), X-ray diffraction (XRD) Fourier transform infrared spectrum (FT-IR) and inductively coupled plasma atomic emission spectrometer (ICP-AES) characterizations all confirm that obtained products are 4ZnO·B2O3·H2O:Ln3+ (Ln=Eu, Tb). The experimental results displayed that the morphology and photoluminescence of compounds is regularly changed with increased the molar amount of rare earth ions. For the Eu3+-doped, Tb3+-doped and Eu3+/Tb3+ co-doped 4ZnO·B2O3·H2O phosphors of morphologies, the rod-like structures gradually changed to flower-like structures, fine wire-like structure and hybrid structure, respectively. To their photoluminescence, the Eu3+ shows a red emission (615nm); the Tb3+ shows a green emission (545nm); for the Eu3+/Tb3+ co-doped 4ZnO·B2O3·H2O phosphors, a combination of blue (5d-4f of Eu2+), green (5D4-7F5 of Tb3+) and red (5D0-7F2 of Eu3+) emissions emerges to achieve white emission. In addition, the energy transfer among Eu3+, Eu2+ and Tb3+ ions was also discussed.
ABSTRACT
Organic phosphonic acids and organic phosphonic acid esters have been of much interest due to their applications in the fields of medicine, agriculture and industrial chemistry. Boronic acids can act as synthetic intermediates and building blocks and are used in sensing, protein manipulation, therapeutics, biological labelling and separation. The additional introduction of an aminophosphonic acid group into a boronic acid may give new opportunities for application. To study the structure of such multifunctional compounds, we prepared two new derivatives which can be easily converted to the corresponding phosphonic acids. In the title compounds, {4-[(butylamino)(diethoxyphosphoryl)methyl]phenyl}boronic acid monohydrate, C15H27BNO5P·H2O, (I), and {4-[(diethoxyphosphoryl)(4-nitroanilino)methyl]phenyl}boronic acid, C17H22BN2O7P, (II), three different substituents are attached to a central C-H group, namely 4-boronophenyl, diethoxyphosphoryl and amine. Compound (I) crystallizes as a monohydrate and OB-H...N hydrogen bonds link neighbouring molecules into chains along the [001] direction. The solvent water molecule connects two such chains running in opposite directions. Compound (II) crystallizes as an ansolvate and classical hydrogen bonds result in a layer structure in the (001) plane.
ABSTRACT
A paramagnetic Sc(3)NC@C(80) anion radical was obtained by chemical reduction. ESR spectrometry and theoretical calculations disclosed that the core NC moiety takes possession of the unpaired electron and stabilizes the paramagnetic species. It is the first time a paramagnetic metal cyanide metallofullerene has been obtained.
ABSTRACT
In the anion of the title molecular salt, C(6)H(9)BNO(2) (+)·C(7)H(4)NO(4) (-), the dihedral angles between the -COO(2-) and -CO(2)H groups and their attached ring are 4.02â (13) and 21.41â (10)°, respectively. The B atom in the cation adopts a syn-syn geometry and the dihedral angle between the -B(OH)(2) group and its attached ring is 11.06â (5)°. In the crystal, O-Hâ¯O, N-Hâ¯O and N-Hâ¯N hydrogen bonds link the components into a three-dimensional network.
ABSTRACT
In the title compound, C(14)H(16)N(2)O(8)·2H(2)O, the complete organic molecule is generated by crystallographic inversion symmetry. The dihedral angles between the aniline ring and the acetic acid groups are almost identical, viz. 82.61â (7) and 80.33â (7)°. In the crystal, O-Hâ¯O hydrogen bonds link the organic mol-ecules and water mol-ecules, forming zigzag chains the c axis. An intra-molecular O-Hâ¯O hydrogen bond is also observed.
ABSTRACT
In the title mol-ecule, C(12)H(10)N(2)O(2), the benzene and pyridine rings form a dihedral angle of 5.01â (8)°. The amide group is twisted by 33.54â (7)° from the plane of the pyridine ring. In the crystal, mol-ecules are linked into centrosymmetric dimers via pairs of O-Hâ¯N hydrogen bonds. N-Hâ¯O hydrogen bonds further link dimers related into chains along the b axis.
ABSTRACT
The title compound, C(12)H(14)N(2)O(4), crystallizes as a zwitterion. A negative charge is delocalized in the deprotonated carboxyl group attached to the pyridine ring. The piperidine N atom accepts a proton and the ring is transformed into a piperidinium cation. There is an intra-molecular N-Hâ¯O hydrogen bond between the protonated NH and a carboxyl-ate O atom. In the crystal, an O-Hâ¯O hydrogen bond between the carboxyl group and the carboxyl-ate O atom of another mol-ecule generates a helix along the b axis.
ABSTRACT
In the title compound, C17H22ClNO·0.5H2O, the water mol-ecule O atom resides on a twofold rotation axis. In the organic mol-ecule, the phenol group forms an intra-molecular O-Hâ¯N hydrogen bond. In the crystal, pairs of organic mol-ecules are hydrogen bonded through bridging solvent water mol-ecules, forming chains along the b-axis direction.
ABSTRACT
In the title compound, C(20)H(22)N(2)O(2), the cyclo-hexane ring adopts a chair conformation and the two N atoms bonded to salicyl-idene groups are in cis positions. Both hy-droxy groups are involved in intra-molecular O-Hâ¯N hydrogen bonding and the two benzene rings form a dihedral angle of 60.5â (1)°.
ABSTRACT
The title compound, C(16)H(20)NO(4)P, crystallizes as a zwitterion. In the mol-ecule, the two aromatic rings form a dihedral angle of 55.2â (1)°. In the crystal, inter-molecular N-Hâ¯O and O-Hâ¯O hydrogen bonds link the mol-ecules into columns propagating in [010].
ABSTRACT
The asymmetric unit of the title co-crystal, C(20)H(16)N(2)·C(18)H(20)O(2), contains one mol-ecule of 4,4'-(cyclo-hexane-1,1-di-yl)diphenol (in which the cyclo-hexane ring adopts a chair conformation) and one mol-ecule of 1-benzyl-2-phenyl-1H-benzimidazole, which are paired through an O-Hâ¯N hydrogen bond. These pairs are further linked by inter-molecular O-Hâ¯O hydrogen bonds into chains along [010]. Weak inter-molecular C-Hâ¯O and C-Hâ¯π inter-actions further consolidate the crystal packing. The dihedral angles between the pendant phenyl rings and the benzimidazole ring are 86.9â (2) and 43.1â (2)°.
ABSTRACT
The Schiff base (E)-4-chloro-2-[(pyridin-2-yl-imino)-meth-yl]phenol was reacted with InCl(3)·4H(2)O, generating the title molecular salt, (C(5)H(7)N(2))(3)[InCl(6)]. The octa-hedral hexa-chlorido-indate(III) anion is located on an inversion centre, and one half of the anion and two crystallographically independent cations form the asymmetric unit. One of the cations is located on a twofold rotation axis and its intra-ring C and N atoms simulate this symmetry by exchanging their positions in statistical disorder. In the crystal, weak N-Hâ¯Cl hydrogen bonds and two types of π-π interactions with centroid-centroid separations of 4.047â (3) and 4.202â (3)â Å are observed.