108-02-1Relevant articles and documents
Delineation and decomposition of energies involved in quaternary ammonium binding in the active site of acetylcholinesterase
Quinn, Daniel M.,Feaster, Shawn R.,Nair, Haridasan K.,Baker, Nathan A.,Radic, Zoran,Taylor, Palmer
, p. 2975 - 2980 (2000)
The quaternary ammonium binding locus in the active site of mammalian acetylcholinesterase is subtended by the side chains of Trp86, Tyr133, Glu202, and Tyr337. Linear free-energy relationships define the interactions involved in molecular recognition by mouse acetylcholinesterase of the quaternary ammonium moiety of ligands. For substrates CH3C(=O)XCH2CH2Y [X = O, Y = CHMe2, or CH2CH3; X = S, Y = H, NH+Me2, or N+Me3] and trifluoroacetophenone transition state analogue inhibitors m-YC6H4C(=O)CF3 [Y = H, Me, Et, iPr, tBu, CF3, NH2, NO2, NMe2, or N+Me3], log(k(cat)/K(m)) and pK(i) depend linearly on the molar refractivity, but not the hydrophobicity, of the substituents Y. These correlations indicate that, in the acylation stage of catalysis, interactions in the quaternary ammonium binding locus stabilize the tetrahedral intermediate (as modeled by transition state analogue affinity) by (5 x 105)-fold (ΔΔG(TI) = -32.5 kJ mol-1) and the transition state by (2 x 104)-fold (ΔΔG(+) = -24.5 kJ mol-1). To evaluate the contribution of cation-π interactions, Trp86 was convened into Tyr, Phe, and Ala by site-specific mutagenesis. For this set of enzymes, a linear free-energy relationship is observed between the pK(i) values for inhibitions by the respective neutral and cationic transition state analogue inhibitors, m-tert-butyltrifluoroacetophenone and m-(N,N,N- trimethylammonio)-trifluoroacetophenone, which indicates that the free energy released on interaction of the quaternary, ammonium moiety with Trp86 arises about equally from cation-π and charge-independent interactions.
Lewis Acid Promoted Aerobic Oxidative Coupling of Thiols with Phosphonates by Simple Nickel(II) Catalyst: Substrate Scope and Mechanistic Studies
Xue, Jing-Wen,Zeng, Miao,Zhang, Sicheng,Chen, Zhuqi,Yin, Guochuan
supporting information, p. 4179 - 4190 (2019/04/30)
Exploring new catalysts for efficient organic synthesis is among the most attractive topics in chemistry. Here, using Ni(OAc)2/LA as catalyst (LA: Lewis acid), a novel catalyst strategy was developed for oxidative coupling of thiols and phosphonates to phosphorothioates with oxygen oxidant. The present study discloses that when Ni(OAc)2 alone was employed as the catalyst, the reaction proceeded very sluggishly with low yield, whereas adding non-redox-active metal ions such as Y3+ to Ni(OAc)2 dramatically promoted its catalytic efficiency. The promotional effect is highly Lewis acidity dependent on the added Lewis acid, and generally, a stronger Lewis acid provided a better promotional effect. The stopped-flow kinetics confirmed that adding Y(OTf)3 can obviously accelerate the activation of thiols by Ni(II) and next accelerate its reaction with phosphonate to generate the phosphorothioate product. ESI-MS characterizations of the catalyst disclosed the formation of the heterobimetallic Ni(II)/Y(III) species in the catalyst solution. Additionally, this Ni(II)/LA catalyst can be applied in the synthesis of a series of phosphorothioate compounds including several commercial bioactive compounds. This catalyst strategy has clearly supported that Lewis acid can significantly improve the catalytic efficiency of these traditional metal ions in organic synthesis, thus opening up new opportunities in their catalyst design.
LIPOCATIONIC POLYMERS AND USES THEREOF
-
Page/Page column 46, (2016/07/05)
Polymers produced by ring opening polymerization which comprises an amino group that can be used in compositions to deliver a nucleic acid such as a miRNA or a siRNA. In some embodiments, compositions which comprise the polymers described herein and a nucleic acid are also provided herein. In some embodiments, these compositions are used to silence one or more genes in vivo or treat a disease or disorder.
Stable-isotope dimethylation labeling combined with LC-ESI MS for quantification of amine-containing metabolites in biological samples
Guo, Kevin,Ji, Chengjie,Li, Liang
, p. 8631 - 8638 (2008/03/15)
One of the challenges associated with metabolome profiling in complex biological samples is to generate quantitative information on the metabolites of interest. In this work, a targeted metabolome analysis strategy is presented for the quantification of amine-containing metabolites. A dimethylation reaction is used to introduce a stable isotopic tag onto amine-containing metabolites followed by LC-ESI MS analysis. This labeling reaction employs a common reagent, formaldehyde, to label globally the amine groups through reductive animation. The performance of this strategy was investigated in the analysis of 20 amino acids and 15 amines by LC-ESI MS. It is shown that the labeling chemistry is simple, fast (13C-dimethylation does not show any isotope effect on either RPLC or HILIC LC, indicating that 13C-labeling is a preferred approach for relative quantification of amine-containing metabolites in different samples. The isotopically labeled 35 amine-containing analogues were found to be stable and proved to be effective in overcoming matrix effects in both relative and absolute quantification of these analytes present in a complicated sample, human urine. Finally, the characteristic mass difference provides additional structural information that reveals the existence of primary or secondary amine functional groups in amine-containing metabolites. As an example, for a human urine sample, a total of 438 pairs of different amine-containing metabolites were detected, at signal-to-noise ratios of greater than 10, by using the labeling strategy in conjunction with RP LC-ESI Fourier-transform ion cyclotron resonance MS.
