Dihydroxy-Acid Dehydratases From Pathogenic Bacteria: Emerging Drug Targets to Combat Antibiotic Resistance.

There is an urgent global need for the development of novel therapeutics to combat the rise of various antibiotic-resistant superbugs. Enzymes of the branched-chain amino acid (BCAA) biosynthesis pathway are an attractive target for novel anti-microbial drug development. Dihydroxy-acid dehydratase (DHAD) is the third enzyme in the BCAA biosynthesis pathway. It relies on an Fe-S cluster for catalytic activity and has recently also gained attention as a catalyst in cell-free enzyme cascades. Two types of Fe-S clusters have been identified in DHADs, i.e. [2Fe-2S] and [4Fe-4S], with the latter being more prone to degradation in the presence of oxygen. Here, we characterise two DHADs from bacterial human pathogens, Staphylococcus aureus and Campylobacter jejuni (SaDHAD and CjDHAD). Purified SaDHAD and CjDHAD are virtually inactive, but activity could be reversibly reconstituted in vitro (up to ∼19,000-fold increase with kcat as high as ∼6.7 s-1 ). Inductively-coupled plasma-optical emission spectroscopy (ICP-OES) measurements are consistent with the presence of [4Fe-4S] clusters in both enzymes. N-isopropyloxalyl hydroxamate (IpOHA) and aspterric acid are both potent inhibitors for both SaDHAD (Ki =7.8 and 51.6 µM, respectively) and CjDHAD (Ki =32.9 and 35.1 µM, respectively). These compounds thus present suitable starting points for the development of novel anti-microbial chemotherapeutics.

Mechanistic Insights into the Thermal Decomposition of Ammonium Perchlorate: The Role of Amino-Functionalized Magnetic Nanoparticles.

This work reports the characterization and application of two promising nanocatalysts for the thermal decomposition of ammonium perchlorate (AP). To obtain these composite materials, magnetite nanoparticles (Fe3O4 NPs) were functionalized with two different amine derivative groups, tertiary amine (Fe3O4 NPs-A1) and quaternary amine. X-ray photoelectron spectroscopy and differential scanning calorimetry provided mechanistic insights into the thermal decomposition of AP. Furthermore, tertiary and quaternary amine groups play a critical role, where the presence of an extra proton could favor an electron-proton transfer as the rate-determining step. Moreover, Fe3O4 NPs-A1 causes a diminution of the high-temperature decomposition of AP positively to 335 °C, increasing the energy release by 278 J g-1 and consequently affording the lowest activation energy (102 kJ mol-1), indicating a low degree of thermal stability, and accelerating the thermal decomposition of AP.

Lanthanide sorbent based on magnetite nanoparticles functionalized with organophosphorus extractants.

In this work, an adsorbent was prepared based on the attachment of organophosphorus acid extractants, namely, D2EHPA, CYANEX 272, and CYANEX 301, to the surface of superparamagnetic magnetite (Fe3O4) nanoparticles. The synthesized nanoparticles were coated with oleic acid, first by a chemisorption mechanism and later by the respective extractant via physical adsorption. The obtained core-shell functionalized magnetite nanoparticle composites were characterized by dynamic light scattering, scanning electron microscopy, transmission electron microscopy, thermogravimetry, infrared absorption and vibrating sample magnetometry. All the prepared nanoparticles exhibited a high saturation magnetization capacity that varied between 72 and 46 emu g-1 and decreased as the magnetite nanoparticle was coated with oleic acid and functionalized. The scope of this study also included adsorption tests for lanthanum, cerium, praseodymium, and neodymium and the corresponding analysis of their results. Sorption tests indicated that the functionalized nanoparticles were able to extract the four studied lanthanide metal ions, although the best extraction performance was observed when the sorbent was functionalized with CYANEX 272, which resulted in a loading capacity of approximately 12-14 mgLa/gMNP. The magnetization of the synthesized nanoparticles was verified during the separation of the lanthanide-loaded sorbent from the raffinate by using a conventional magnet.

The effects of emotions on the disposition to normative and non-normative political action in the context of the Chilean post-social outburst.

This article analyzes the role of Chileans' emotions as predictors of normative and non-normative political action in the context of the post-social outbreak and the constituent process. We carried out three descriptive studies: first, a study conducted 1 year after the social outburst (n = 607), a second one carried out before the constitutional referendum (n = 320), and a third study conducted after the constitutional referendum (n = 210). The results indicated that participants present a higher disposition to normative over non-normative political action, although both lose strength as the studies temporally move away from the social outburst. Also, our research established that emotions directed towards different events related to the Chilean political process play a conspicuous role in predicting the disposition to mobilize in a normative and non-normative way.

Evaluation of Mono and Bimetallic Ferrocene-Based 1,2,3-Triazolyl Compounds as Burning Rate Catalysts for Solid Rocket Motor.

We reported mono and bimetallic ferrocene-based 1,2,3-triazolyl compounds as potential burning rate catalysts in their neutral and ionic forms. All complexes reported here were characterized using 1H and 13C NMR, elemental analysis, and Mössbauer spectroscopy, which was performed for neutral and oxide compounds. The complexes present quasireversible redox potentials with higher oxidative ability than ferrocene and catocene under the same conditions. The complexes were tested as catalysts on the thermal decomposition of ammonium perchlorate (AP) and examined by a differential scanning calorimetry technique to gain further knowledge about their catalytic behavior. Compound 1 causes a decrease of the high-temperature decomposition (HTD) of AP positively, decreasing the decomposition temperature of AP to 345 °C and consequently increasing the energy release to 1939 J·g-1. We took the residues from the pans after testing from the DSC to elucidate the underlying reaction pathways. We obtained the size of the nanostructures formed after thermal decomposition of AP determined by the TEM technique. The diameter and size distribution of iron oxide nanoparticles formed depend on the alkyl sidechain of the triazolium ring, which induces the formation of nanoparticles with a double diameter and size distribution compared to their neutral analogues, suggesting that the possible intermediate for the mechanism degradation of AP by ferrocene derivatives is nanoscale Fe2O3 or similar oxides.

Cluster of Hexamolybdenum [Mo6Cl14]2- for Sensing Nitroaromatic Compounds.

This contribution describes a novel method for the detection of trace amounts of trinitrotoluene (TNT) using a cluster of hexamolybdenum with general formula [Mo6Cl14]2-. The molybdenum cluster was characterized by UV-visible, FT-IR, and fluorescence techniques, and the synthesis was efficient and reproducible. The evaluation of the molybdenum cluster by TNT detection was perfomed by fluoresecent measurements, and the results were interpreted by the Stern-Volmer equation, obtaining K SV values of 2.9 × 105 and 1.6 × 104 M-1 in different concentration ranges. Further, the results suggest that at TNT concentrations higher than 4 × 10-5 mM (0.01 mg L-1) it is possible to measure the quenching of the cluster fluorescence. The DFT calculations indicate that the contribution of the TNT in the active lowest unoccupied molecular orbitals that are involved in the higher intensity transitions in the complex cluster-TNT are significant. This situation differs from all the luminescent [M6X8L6]2- clusters (M = Mo; X = facial bridging ligand, and L = labile axial ligands), where most of the closely spaced excited states are located in the {M6X8} q+ core. Thus, the TNT switches off the cluster luminescence. The approach using a [Mo6Cl14]2--based fluorescence sensor has the potential to be a sensing technology for the detection of nitroaromatic explosives.