128837-56-9Relevant articles and documents
Catalytic Hydrogenolysis of Substituted Diaryl Ethers by Using Ruthenium Nanoparticles on an Acidic Supported Ionic Liquid Phase (Ru@SILP-SO3H)
Rengshausen, Simon,Etscheidt, Fabian,Gro?kurth, Johannes,Luska, Kylie L.,Bordet, Alexis,Leitner, Walter
supporting information, p. 405 - 412 (2019/02/26)
Catalytic hydrogenolysis of diaryl ethers is achieved by using ruthenium nanoparticles immobilized on an acidic supported ionic liquid phase (Ru@SILP-SO 3 H) as a multifunctional catalyst. The catalyst components are assembled through a molecular approach ensuring synergistic action of the metal and acid functions. The resulting catalyst is highly active for the hydrogenolysis of various diaryl ethers. For symmetric substrates such as diphenyl ether, hydrogenolysis is followed by full hydrodeoxygenation producing the corresponding cycloalkanes as the main products. For unsymmetric substrates, the cleavage of the C-O bond is regioselective and occurs adjacent to the unsubstituted phenyl ring. As hydrogenation of benzene is faster than hydrodeoxygenation over the Ru@SILP-SO 3 H catalyst, controlled mixtures of cyclohexane and substituted phenols are accessible with good selectivity. Application of Ru@SILP-SO 3 H catalyst in continuous-flow hydrogenolysis of 2-methoxy-4-methylphenoxybenzene is demonstrated with use of commercial equipment.
Inhibition of the Bacterial Enoyl Reductase FabI by Triclosan: A Structure-Reactivity Analysis of FabI Inhibition by Triclosan Analogues
Sivaraman, Sharada,Sullivan, Todd J.,Johnson, Francis,Novichenok, Polina,Cui, Guanglei,Simmerling, Carlos,Tonge, Peter J.
, p. 509 - 518 (2007/10/03)
To explore the molecular basis for the picomolar affinity of triclosan for FabI, the enoyl reductase enzyme from the type II fatty acid biosynthesis pathway in Escherichia coli, an SAR study has been conducted using a series of triclosan analogues. Triclosan (1) is a slow, tight-binding inhibitor of FabI, interacting specifically with the E·NAD+ form of the enzyme with a K1 value of 7 pM. In contrast, 2-phenoxyphenol (2) binds with equal affinity to the E·NAD+ (K1 = 0.5 μM) and E·NADH (K2 = 0.4 μM) forms of the enzyme and lacks the slow-binding step observed for triclosan. Thus, removal of the three triclosan chlorine atoms reduces the affinity of the inhibitor for FabI by 70 000-fold and removes the preference for the E·NAD+ FabI complex. 5-Chloro-2-phenoxyphenol (3) is a slow, tight-binding inhibitor of FabI and binds to the E· NAD+ form of the enzyme (K1 = 1.1 pM) 7-fold more tightly than triclosan. Thus, while the two ring B chlorine atoms are not required for FabI inhibition, replacement of the ring A chlorine increases binding affinity by 450 000-fold. Given this remarkable observation, the SAR study was extended to the 5-fluoro-2-phenoxyphenol (4) and 5-methyl-2-phenoxyphenol (5) analogues to further explore the role of the ring A substituent. While both 4 and 5 are slow, tight-binding inhibitors, they bind substantially less tightly to FabI than triclosan. Compound 4 binds to both E·NAD+ and E·NADH forms of the enzyme with K 1 and K2 values of 3.2 and 240 nM, respectively, whereas compound 5 binds exclusively to the E·NADH enzyme complex with a K 2 value of 7.2 nM. Thus, the ring A substituent is absolutely required for slow, tight-binding inhibition. In addition, pKa measurements coupled with simple electrostatic calculations suggest that the interaction of the ring A substituent with F203 is a major factor in governing the affinity of analogues 3-5 for the FabI complex containing the oxidized form of the cofactor.
