查看更多>>摘要：? 2022 Elsevier Inc.Resistant bacteria represent an urgent worldwide threat. NDM-1-producing strains are rendering the last line antibiotics less effective. Six bismuth complexes of general formula BiLCl2, where L is a thiosemicarbazone bearing a quinoline moiety, have been synthesized and fully characterized, including their X-ray crystal structures. The synergistic relationship between the compounds and meropenem have been tested in a combination therapy in carbapenem-resistant Klebsiella pneumoniae (NTCT14331) carrying the NDM-1 gene. Quinoline-2-carboxaldehyde-N4-phenyl-3-thiosemicarbazone bismuth dichloride and carbapenem showed synergism in a dose dependent manner with negligible antibacterial activity when used in a monotherapy and could restore antibiotic sensitivity in the strain producing NDM-1 enzyme. The minimum inhibitory concentration (MIC) of meropenem lowered down 128 folds up to 2 μgmL?1, a concentration lower to the sensitivity level. The IC50 of the compound against A549 human lung carcinoma cells and HuDe human epithelial tissue was 46.96 ± 16.66 μM and 54.26 ± 9.89 μM respectively. The cytotoxicity against human cells was higher than the effective concentration needed for the synergistic effect in bacterial cells, indicating that a structural optimization of the compounds is needed.
查看更多>>摘要：? 2022 Elsevier Inc.In this work, we report on the development of fluorescent half-sandwich iridium complexes using a fluorophore attachment strategy. These constructs consist of pentamethylcyclopentadienyl (Cp*) iridium units ligated by picolinamidate donors conjugated to green-emitting boron-dipyrromethene (bodipy) dyes. Reaction studies in H2O/THF mixtures showed that the fluorescent Ir complexes were active as catalysts for transfer hydrogenation, with activities similar to that of their non-fluorescent counterparts. The iridium complexes were taken up by NIH-3T3 mouse fibroblast cells, with 50% inhibition concentrations ranging from ~20–70 μM after exposure for 3 h. Visualization of the bodipy-functionalized Ir complexes in cells using fluorescence microscopy revealed that they were localized in the mitochondria and lysosome but not the nucleus. These results indicate that our fluorescent iridium complexes could be useful for future biological studies requiring intracellular catalyst tracking.
查看更多>>摘要：? 2022 Elsevier Inc.The N-terminus of nickel-dependent superoxide dismutase (NiSOD) forms a structural motif known as the “Ni-hook,” where the peptide wraps around the metal to bring cysteine-2 and cysteine-6 into spatial proximity, allowing these residues to coordinate in a cis-geometry. A highly conserved proline-5 residue in the Ni-hook adopts a cis-conformation that is widely considered important for its formation. Herein, we investigate this role by point mutation of Pro5 to alanine. The results obtained show that the variant exhibits wild-type-like redox catalysis and features a Ni(III) center very similar to that found in enzyme. Structural analysis using X-ray absorption spectroscopy of the nickel sites in as-isolated P5A-NiSOD reveals changes in the variant and are consistent with a six-coordinate Ni site with (N/O)4S2 coordination. These changes are attributed to changes in the Ni(II) site structure. Nickel-binding studies using isothermal titration calorimetry reveal two binding events with Kd = 25(20) nM, and 250(60) nM. These events are attributed to i) Ni(II) binding to a preformed Ni-hook containing cis-Pro5 and ii) the combination of trans- to cis- isomerization upon Ni(II) binding, respectively. The higher-affinity binding event is absent in P5A-NiSOD, an observation attributed to the low abundance of the cis-Ala5 isomer in the apo-protein.
查看更多>>摘要：? 2022 Elsevier Inc.The enzyme, Formate Dehydrogenase, is biological catalyst responsible for the hydrogenation of carbon dioxide to formic acid. The present research has discovered CO2 reduction activities and their application using certain metal containing (Mo- or W-)/ NAD + -linked Formate Dehydrogenases. However, the enzyme must be immobilized for easy separation, increased stability and reusability. The shortcomings associated with conventional immobilization method include leaching, mass transfer limitation and low activity. We here present a perspective, wherein, we assess the efficacy of soft-oxometalates and macrocycles as a promising alternative to Formate Dehydrogenase immobilization. The mechanistic pathway and stability of Formate Dehydrogenase from different sources are discussed and compared with their tailored ‘chemical counterparts’ soft-oxometalates and macrocycles based systems such as {Mo132}, {Mo154}, {MoV9}, Co and Mn based Corroles. The structure, properties and mechanism of CO2 reduction by different Soft-oxometalates and metal based macrocycles were found to be synonymous with that of metal based Formate Dehydrogenase. We comprehensively summarize different reported approaches to valorize CO2 to C1 and C2 products such as photochemical, electrochemical and systems chemistry to showcase our efforts in the ongoing pursuit of CO2 valorization, inspired by the workings of such enzymes, alongside the efforts of several other leading groups. The revelatory insights in the perspective could be used not only for developing bio-inspired CO2 Reduction Reaction but also constructing artificial cell automata for artificial life like system.
查看更多>>摘要：? 2022 Elsevier Inc.Cadmium (Cd) is a widely used heavy metal which is reported to exert extensive harm to the environment and human health. Owing to Cd being an element it is continuously enriched in the environment. The mechanism of splenic toxicity by Cd, however, is not yet clear. In order to explore the toxic mechanism of Cd exposure to the spleen, we added 0, 35, 70 and 140 mg/kg of Cd to the diet of chicken and fed them this diet for 90 days. Analysis of histopathological sections showed that Cd exposure damaged the spleen structure, the spleen red pulp, the white pulp boundary disappeared and the number of lymphocytes decreased significantly, suggesting that Cd exposure leads to organ injury to the spleen. Particularly, Cd-induced anoikis - a special form of programmed cell death caused by the loss of contact between cells and extracellular matrix and other cells - is associated with integrin-related cell detachment and activation of apoptotic signaling pathways. Moreover, Cd exposure leads to an increase in free radicals content and affects the activity of antioxidant enzymes resulting in oxidative stress. Simultaneously, Cd activated the body's antioxidant defense system mediated by the Nuclear factor related factor 2 (Nrf2) signaling pathway. Based on our results Cd-induced splenic lymphocytes anoikis is not mitigated by Nrf2-mediated antioxidative defense response.
Black C.M.Chu A.J.Routledge A.Duhme-Klair A.-K....
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查看更多>>摘要：? 2022 The AuthorsA novel Trojan Horse conjugate consisting of an SO2-releasing 2,4-dinitrobenzenesulfonamide group attached to the monocatecholate siderophore aminochelin was synthesized to examine whether a bidentate catecholate siderophore unit could help potentiate the antimicrobial activity of SO2-releasing prodrugs. The conjugate obtained displays rapid SO2 release on reaction with glutathione, and proved more active against Staphylococcus aureus than a comparable SO2-releasing prodrug lacking the siderophore unit, although activity required micromolar concentrations. The conjugate was inactive against wild-type Escherichia coli, but activity was observed against an entA mutant strain that is unable to produce its major siderophores. Hence, the poor activity of the conjugate in wild-type E. coli may be due to the production of native siderophores that can compete with the conjugate for iron binding and uptake.
查看更多>>摘要：? 2022 Elsevier Inc.The SARS-CoV-2 main protease (Mpro) is responsible for cleaving twelve nonstructural proteins from the viral polyprotein. Mpro, a cysteine protease, is characterized by a large number of noncatalytic cysteine (Cys) residues, none involved in disulfide bonds. In the absence of a tertiary-structure stabilizing role for these residues, a possible alternative is that they are involved in redox processes. We report experimental work in support of a proposal that surface cysteines on Mpro can protect the active-site Cys145 from oxidation by reactive oxygen species (ROS). In investigations of enzyme kinetics, we found that mutating three surface cysteines to serines did not greatly affect activity, which in turn indicates that these cysteines could protect Cys145 from oxidative damage.
查看更多>>摘要：? 2021In this study, a new tetra-substituted phthalonitrile (diethyl 2-(2-chloro-4,5-dicyano-3,6-bis(hexyloxy)phenyl)malonate) bearing three different substituents was synthesized and characterized. Due to the basic medium, transesterification occurred during the synthesis of the target phthalocyanines [M = Zn (II), Cu (II), Co (II), In (III), Lu (III)] in n-pentanol and the ethyl groups were replaced with pentyl groups. The biological features of the resultant compounds were studied for the first time in this study. All the compounds exhibited high antioxidant, antimicrobial, and DNA cleavage activities. The highest antioxidant activity was obtained 90.39% for lutetium phthalocyanine at 100 mg/L. The most effective MIC value was obtained 8 mg/L against Candida parapisilosis. The most effective microbial cell viability inhibition was obtained 100% for cobalt and lutetium phthalocyanines. They exhibited excellent biofilm inhibiton activities. Higher biofilm inhibition was achieved using light irradiation. The compounds exhibited higher biofilm inhibition activities with photodynamic against Staphylococcus aureus compared with Pseudo aureginosa.
查看更多>>摘要：? 2022 Elsevier Inc.A sensitive and selective photoluminescent sensor based on the highly charged monoruthenium(II) complex was designed to detect dopamine (DA) in aqueous samples. Two novel highly charged cationic ruthenium(II) complexes [Ru(bpy)2(bpy-N)]X4 (bpy = 2,2′-bipyridine, bpy-N = 4,4′-bis[N,N,N-triethyl-(methylamino)]-2,2′-bipyridine, X? = [PF6]? (1a) or Cl? (1b) and [Ru(bpy)(bpy-N)2]X6 (X? = [PF6]? (2a) or Cl?(2b)) can be assembled with anionic surfactant sodium dodecylbenzene sulfonate (SDBS), leading to an enhancement of photoluminescence intensity. Upon addition of DA to the system, the photoluminescence intensity of the assembled system was quenched due to the energy transfer effect. It exhibited a wide linear range (0.1–50 μM) and low detection limit (10 nM). The sensor demonstrated a high selectivity toward DA, especially in the presence of adrenaline (Adr) and norepinephrine (NE), whose structures are similar to DA in biological systems. With the merits of simple operation, obvious phenomenon and fast response speed, the sensor had a potential application prospect in human urine sample.
查看更多>>摘要：? 2022 Elsevier Inc.We examine Hofmeister specific ion effects of electrolytes added to protein solution under conditions minimizing electrostatic attraction between cations and positively charged protein. Hemoglobin (Hb) in aqueous solution at the denaturing pH = 2.7 is investigated in the presence of several metal chlorides, along with sodium and potassium bromides, iodides and thiocyanates, using electrospray ionization mass spectrometry (ESI-MS). Salt concentration was varied to maximize peak intensity and bell-shaped profile in the ESI-MS spectrum. The α-chain of myoglobin is identified as the main pattern of the ESI-MS spectra in all Hb-salt systems. Both peak intensity and quality of the bell-shaped profile of the protein spectrum decrease in the cation order: K+ > > Mg2+ > Li+ > > Na+ > Ca2+ ≈ Cs+ > Rb+ for Hb-Metal Chloride systems, and decrease in the anion order: Cl? > Br? > I? > SCN? for systems of both Hb-NaX and Hb-KX salts. To quantify salt addition effects two Hofmeister specific electrolyte parameters HS, and PS are proposed. HS is the mean (Hb-salt)/Hb peak intensity ratio, measured for the nine peaks used for ESI-MS spectra deconvolution, taken at the same m/z values of the Hb profile. PS is the ratio between HS standard deviation and HS, and provides a specific perturbation parameter measuring the loss of protein structure. These two Hofmeister parameters give clear evidence of the effects induced either by KCl, MgCl2 and LiCl that enhance protein peak intensity, or by NaBr, NaI, NaSCN and KSCN that induce the protein fragmentation, due to electrolyte-mediated dissociation.
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