The development of multidrug resistant (MDR) and extensively drug resistant (XDR) forms of tuberculosis (TB) has stimulated research efforts globally to expand the new drug pipeline. Nitro aromatic compounds, including 1, 3-Benzothiazin-4-ones (BTZs) and related agents, are a promising new class for the treatment of TB. Research has shown that the nitroso intermediates of BTZs that are generated in vivo cause suicide inhibition of decaprenylphosphoryl-β-D-ribose 2′ oxidase (DprE1), which is responsible for cell wall arabinogalactan biosynthesis. We have designed and synthesized novel anti-TB agents inspired from BTZs and other nitroaromatic compounds. Computational studies indicated that the unsubstituted aromatic carbons of BTZ043 and related nitroaromatic compounds are the most electron deficient and might be prone to nucleophilic attack. Our chemical studies on BTZ043 and the additional nitro aromatic compounds synthesized by us and the others confirmed the postulated reactivity. The results indicate that nucleophiles such as thiolates, cyanide and hydride induce non-enzymatic reduction of the nitro groups present in these compounds to the corresponding nitroso intermediates by addition at the unsubstituted electron deficient aromatic carbon present in these compounds. Furthermore we demonstrate here that these compounds are good candidates for the classical von Richter reaction. These chemical studies offer an alternate hypotheses for the mechanism of action of nitro aromatic anti-TB agents in that the cysteine thiol(ate) or a hydride source at the active site of DprE1 may trigger the reduction of the nitro groups in a manner similar to the von Richter reaction to the nitroso intermediates, to initiate the inhibition of DprE1.
While paper is an excellent material for use in many
other portable
sensors, potentiometric paper-based sensors have been reported to
perform worse than conventional rod-shaped electrodes, in particular
in view of limits of detection (LODs). Reported here is an in-depth
study of the lower LOD for Cl– measurements with
paper-based devices comprising AgCl/Ag transducers. Contamination
by Cl– from two commonly used device materialsa
AgCl/Ag ink and so-called ashless filter paperwas found to
increase the concentration of Cl– in paper-contained
samples far above what is expected for the spontaneous dissolution
of the transducer’s AgCl, thereby worsening lower LODs. In
addition, for the case of Ag+, the commonly hypothesized
adsorption of metal cations onto filter paper was found not to significantly
affect the performance of AgCl/Ag transducers. We note that in the
context of chemical analysis, metal impurities of paper are often
mentioned in the literature, but Cl– contamination
of paper has been overlooked.
Responding to current limitations in paper‐based sensors and the increased interest in wearable sensors, we introduce here potentiometric sensors fully integrated into a knitted polyester fabric and their application in aqueous and biological samples. Single layer ion‐sensing devices requiring only 30 μL of sample were fabricated using wax patterning and Ag/AgCl paint. These devices give a Nernstian response to chloride over 4 orders of magnitude – an order of magnitude improvement from analogous paper‐based devices. We also report the penetration of polyester yarns with polymeric hydrophobic and hydrophilic ion‐sensing and reference membranes, all fully embedded within the fabric. These results demonstrate the promise of knitted fabrics as substrates for fully‐integrated potentiometric sensors with improved detection limits. They also elucidate the effect of pore structure on sensor fabrication and performance, thereby affecting how we understand both fabric‐ and paper‐based devices.
The cover feature shows the design of a novel textile‐based ion‐selective electrode platform to monitor ion concentrations in 30 μL samples of blood. This is the first report of a fully‐integrated textile‐based potentiometric sensor in which all sensing and reference components are embedded into the underlying support fabric. More information can be found in the Full Paper by P. Bühlmann and E. J. Herrero.
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