448898-42-8Relevant articles and documents
Zn148 is a modular synthetic metallo-β-lactamase inhibitor that reverses carbapenem resistance in Gram-negative pathogens in vivo
Andresen, Adriana Magalhaes Santos,Bayer, Annette,Carlsen, Trine Josefine Olsen,Finke, Sarah,Heikal, Adam,Huber, Sandra,Kildahl-Andersen, Geir,Lauksund, Silje,Leiros, Hanna-Kirsti S.,Schnaars, Christian,Skagseth, Susann,?strand, Ove Alexander H?gmoen,?kstad, Ole Andreas,Fr?hlich, Christopher,Gj?en, Tor,Rongved, P?l,Samuelsen, ?rjan
, (2020)
Carbapenem-resistant Gram-negative pathogens are a critical public health threat and there is an urgent need for new treatments. Carbapenemases (β- lactamases able to inactivate carbapenems) have been identified in both serine β-lactamase (SBL) and metallo-β-lactamase (MBL) families. The recent introduction of SBL carbapenemase inhibitors has provided alternative therapeutic options. Unfortunately, there are no approved inhibitors of MBL-mediated carbapenem-resistance and treatment options for infections caused by MBL-producing Gram-negatives are limited. Here, we present ZN148, a zinc-chelating MBL-inhibitor capable of restoring the bactericidal effect of meropenem and in vitro clinical susceptibility to carbapenems in >98percent of a large international collection of MBL-producing clinical Enterobacterales strains (n = 234). Moreover, ZN148 was able to potentiate the effect of meropenem against NDM-1-producing Klebsiella pneumoniae in a murine neutropenic peritonitis model. ZN148 showed no inhibition of the human zinc-containing enzyme glyoxylase II at 500 μM, and no acute toxicity was observed in an in vivo mouse model with cumulative dosages up to 128 mg/kg. Biochemical analysis showed a time-dependent inhibition of MBLs by ZN148 and removal of zinc ions from the active site. Addition of exogenous zinc after ZN148 exposure only restored MBL activity by -30percent, suggesting an irreversible mechanism of inhibition. Mass-spectrometry and molecular modeling indicated potential oxidation of the active site Cys221 residue. Overall, these results demonstrate the therapeutic potential of a ZN148-carbapenem combination against MBL-producing Gram-negative pathogens and that ZN148 is a highly promising MBL inhibitor that is capable of operating in a functional space not presently filled by any clinically approved compound.
Wavelength conversion lanthanide(III)-cored complex for highly efficient dye-sensitized solar cells
Oh, Jung Hwan,Song, Hae Min,Eom, Yu Kyung,Ryu, Jung Ho,Ju, Myung Jong,Kim, Hwan Kyu
experimental part, p. 2743 - 2750 (2012/02/01)
Lanthanide(III)-cored complex as a wavelength conversion material has been successfully designed and synthesized for highly efficient dye-sensitized solar cells, for the first time, since light with a short wavelength has not been effectively used for generating electric power owing to the limited absorption of these DSSCs in the UV region. A black dye (BD) was chosen and used as a sensitizer, because BD has a relatively weak light absorption at shorter wavelengths. The overall conversion efficiency of the BD/WCM device was remarkably increased, even with the relatively small amount of WCM added to the device. The enhancement in Voc by WCM, like DCA, could be correlated with the suppression of electron recombination between the injected electrons and I3 - ions. Furthermore, the short-circuit current density was significantly increased by WCM with a strong UV light-harvesting effect. The energy transfer from the Eu(III)-cored complex to the TiO2 film occurred via the dye, so the number of electrons injected into the TiO2 surface increased, i.e., the short-circuit current density was increased. As a result, BD/WCM-sensitized solar cells exhibit superior device performance with the enhanced conversion efficiency by a factor of 1.22 under AM 1.5 sunlight: The photovoltaic performance of the BD/WCM-based DSSC exhibited remarkably high values, Jsc of 17.72 mA/cm2, Voc of 720 mV, and a conversion efficiency of 9.28% at 100 mW cm-2, compared to a standard DSSC with Jsc of 15.53 mA/cm2, Voc of 689 mV, and a conversion efficiency of 7.58% at 100 mW cm-2. Therefore, the Eu(III)-cored complex is a promising candidate as a new wavelength conversion coadsorbent for highly efficient dyesensitized solar cells to improve UV light harvesting through energy transfer processes. The abstract should be a single paragraph which summaries the content of the article.
Spectroscopic properties, electrochemistry, and reactivity of Mo0, MoI, and MoIIcomplexes with the [Mo(bpa)(CO)3] unit [bpa = bis(2-picolyl)aminel and their application for the labelling of peptides
Van Staveren, Dave R.,Bothe, Eberhard,Weyhermueller, Thomas,Metzler-Nolte, Nils
, p. 1518 - 1529 (2007/10/03)
The synthesis of the complexes [Mo(bpa)(CO)3] (1) and [Mo(Bz-bpa)(CO)3] (2) [bpa = bis(2-picolyl)amine; Bz-bp= N-benzylbis(2-picolyl)amine] is described. These compounds have been characterized by spectroscopic techniques including m
