Electric Literature of 108-47-4, Catalysts function by providing an alternate reaction mechanism that has a lower activation energy than would be found in the absence of the catalyst. In some cases, the catalyzed mechanism may include additional steps.In a article, 108-47-4, molcular formula is C7H9N, introducing its new discovery.
Design, synthesis, and crystal structures of 6-alkylidene-2?- substituted penicillanic acid sulfones as potent inhibitors of acinetobacter baumannii OXA-24 carbapenemase
Class D beta-lactamases represent a growing and diverse class of penicillin-inactivating enzymes that are usually resistant to commercial beta-lactamase inhibitors. As many such enzymes are found in multi-drug resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa, novel beta-lactamase inhibitors are urgently needed. Five unique 6-alkylidene-2?-substituted penicillanic acid sulfones (1-5) were synthesized and tested against OXA-24, a clinically important beta-lactamase that inactivates carbapenems and is found in A. baumannii. Based upon the roles Tyr112 and Met223 play in the OXA-24 beta-lactamase, we also engineered two variants (Tyr112Ala and Tyr112Ala,Met223Ala) to test the hypothesis that the hydrophobic tunnel formed by these residues influences inhibitor recognition. IC50 values against OXA-24 and two OXA-24 beta-lactamase variants ranged from 10 ¡À 1 (4 vs WT) to 338 ¡À 20 nM (5 vs Tyr112Ala, Met223Ala). Compound 4 possessed the lowest Ki (500 ¡À 80 nM vs WT), and 1 possessed the highest inactivation efficiency (kinact/ Ki = 0.21 ¡À 0.02 muM-1 s-1). Electrospray ionization mass spectrometry revealed a single covalent adduct, suggesting the formation of an acyl-enzyme intermediate. X-ray structures of OXA-24 complexed to four inhibitors (2.0-2.6 A) reveal the formation of stable bicyclic aromatic intermediates with their carbonyl oxygen in the oxyanion hole. These data provide the first structural evidence that 6-alkylidene-2?-substituted penicillin sulfones are effective mechanism-based inactivators of class D beta-lactamases. Their unique chemistry makes them developmental candidates. Mechanisms for class D hydrolysis and inhibition are discussed, and a pathway for the evolution of the BlaR1 sensor of Staphylococcus aureus to the class D beta-lactamases is proposed.
The proportionality constant is the rate constant for the particular unimolecular reaction. the reaction rate is directly proportional to the concentration of the reactant. I hope my blog about 108-47-4 is helpful to your research. Electric Literature of 108-47-4
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Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis