Since their discovery over five decades ago, quinolone antibiotics have found enormous success as broad spectrum agents that exert their activity through dual inhibition of bacterial DNA gyrase and topoisomerase IV. Increasing rates of resistance, driven largely by target-based mutations in the GyrA/ParC Quinolone Resistance Determining Region, have eroded the utility and threaten the future use of this vital class of antibiotics. Herein we describe the discovery and optimization of a series of 4-(aminomethyl)quinolin-2(1H)-ones, exemplified by 34, that inhibit bacterial DNA gyrase and topoisomerase IV and display potent activity against ciprofloxacin-resistant Gramnegative pathogens. X-ray crystallography reveals that 34 occupies the classical quinolone binding site in the topoisomerase IV-DNA cleavage complex, but does not form significant contacts with residues in the Quinolone Resistance Determining Region.
Protective fabrics with air-permeable and flexible features are crucial for practical application in the detoxification of chemical warfare agents (CWAs). Zr-based metal−organic frameworks (Zr-MOFs) are desirable to exhibit outstanding degradation toward CWAs. However, generally, MOFs with powders cannot afford the utilization as a protective layer directly; meanwhile, it is still a puzzling challenge to integrate MOFs with textiles efficiently. Herein, we develop a scalable and controllable strategy to fabricate UiO-66-NH 2 on electrospun polyacrylonitrile nanofibers (UiO-66-NH 2 fabrics) firmly and uniformly to capture and catalyze 2chloroethyl ethyl sulfide (CEES) effectively for self-detoxification. The obtained UiO-66-NH 2 fabrics are greatly capable of specific surface area, ample porosity, excellent crystallinity, and abundant catalytic active sites. Consequently, CEES can be removed efficiently up to 97.7% after 48 h by reaction and adsorption. The degradation products mainly including ethyl-2-hydroxyethyl sulfide, ether, bis [2-(ethylthio)ethyl], and 2-(2-(ethylthio)ethylamino) terephthalic acid are detected. Moreover, the obtained nanofibrous fabrics possess air-permeable, washable, and flexible as well as lightweight merits, totally ensuring their promising engineering applications for protective clothing.
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