Development of Solvent-Dispersible Coordination Polymer Nanocrystals and Application as Efficient Heterogeneous Catalysts

Nonporous coordination polymers (CPs) constructed from flexible bridging ligands have seldom been utilized in practical applications, owing to limited solubility and/or stability in most solvents. Here we have produced nanocrystal coordination polymers (NCPs) with identical crystalline structure to their macroscale counterparts, high solvent dispersibility, and large effective surface area for catalytic application. A microemulsion system has been developed for the mild synthesis of the Zn^II- and Cu^II-NCPs, resulting in control over the size, morphology, and reactivity. Both Zn^II- and Cu^II-NCPs demonstrated high catalytic activity in a ring opening reaction of cyclohexene oxide with aniline; furthermore, reduced Cu-NCPs were employed as efficient, reusable catalysts for an azide–alkyne cycloaddition “click” reaction in the nonpolar solvent heptane. In contrast, all macroscale CP equivalents, prepared by conventional methods, were catalytically inactive

Biochemical and Cellular Characterization of the Function of Fluorophosphonate-Binding Hydrolase H (FphH) in <i>Staphylococcus aureus</i> Support a Role in Bacterial Stress Response

The development of new treatment options for bacterial infections requires access to new targets for antibiotics and antivirulence strategies. Chemoproteomic approaches are powerful tools for profiling and identifying novel druggable target candidates, but their functions often remain uncharacterized. Previously, we used activity-based protein profiling in the opportunistic pathogen Staphylococcus aureus to identify active serine hydrolases termed fluorophosphonate-binding hydrolases (Fph). Here, we provide the first characterization of S. aureus FphH, a conserved, putative carboxylesterase (referred to as yvaK in Bacillus subtilis) at the molecular and cellular level. First, phenotypic characterization of fphH-deficient transposon mutants revealed phenotypes during growth under nutrient deprivation, biofilm formation, and intracellular survival. Biochemical and structural investigations revealed that FphH acts as an esterase and lipase based on a fold well suited to act on a small to long hydrophobic unbranched lipid group within its substrate and can be inhibited by active site-targeting oxadiazoles. Prompted by a previous observation that fphH expression was upregulated in response to fusidic acid, we found that FphH can deacetylate this ribosome-targeting antibiotic, but the lack of FphH function did not infer major changes in antibiotic susceptibility. In conclusion, our results indicate a functional role of this hydrolase in S. aureus stress responses, and hypothetical functions connecting FphH with components of the ribosome rescue system that are conserved in the same gene cluster across Bacillales are discussed. Our atomic characterization of FphH will facilitate the development of specific FphH inhibitors and probes to elucidate its physiological role and validity as a drug target