A new, moderately hydrophobic, single-isomer charged cyclodextrin, the sodium salt of heptakis(2,3-diacetyl-6sulfato)--cyclodextrin, has been synthesized and used to separate a variety of neutral, weak acid, strong base, weak base, and zwitterionic racemic enantiomers in low-pH and high-pH background electrolytes. Separation selectivity for the netural analytes rapidly decreases as the concentration of heptakis(2,3-diacetyl-6-sulfato)--cyclodextrin increases. For charged analytes, selectivity can increase, decrease, or pass a maximum, depending on the numeric values of the respective complexation constants and ionic mobilities. In addition to separation selectivity, the extent of peak resolution that can be realized strongly depends on the magnitude of the dimensionless electroosmotic flow. Heptakis(2,3-diacetyl-6-sulfato)--cyclodextrin proved to be a broadly applicable chiral resolving agent.

The third member of a new family of single-isomer charged cyclodextrins, the sodium salt of heptakis(2,3-dimethyl-6-sulfato)-β-cycldextrin, has been synthesized, characterized, and used for the capillary electrophoretic separation of the enantiomers of neutral, acidic, basic, and zwitterionic analytes. Though heptakis(2,3-dimethyl-6-sulfato)-β-cyclodextrin complexes much less strongly with any of the analytes tested here than the previously synthesized heptakis(2,3-diacetyl-6-sulfato)-β-cyclodextrin and heptakis-6-sulfato-β-cyclodextrin, it offers excellent enantioselectivities, complementary to those of the other two single-isomer, differently functionalized charged cyclodextrins. Confirming the predictions of the charged resolving agent migration model, heptakis(2,3-dimethyl-6-sulfato)-β-cyclodextrin allowed for the reversal of the migration order of the enantiomers of neutral analytes as the cyclodextrin concentration was increased. Just as with the previous two single-isomer charged resolving agents, separation selectivity for the acidic, basic, and zwitterionic analytes could increase, decrease, or pass a maximum as the cyclodextrin concentration was increased, depending on the respective binding strength of the enantiomers and the ionic mobilities of both the complexed and noncomplexed forms of the enantiomers.

Liver regeneration is a rapid and concerted response to injury, in which growth factor-generated intracellular signals result in activation of transcription factors, DNA synthesis, and hepatocyte proliferation. However, the link between cytoplasmic signals resulting in proliferative response to liver injury remains to be elucidated. We show here that association of Gab1 adaptor protein and Shp2 tyrosine phosphatase is a critical event at the early phase of liver regeneration. Partial hepatectomy (PH) rapidly and transiently induced assembly of a complex comprising Shp2 and tyrosine-phosphorylated Gab1 in wild-type hepatocytes. Consistently, liver-specific Shp2 knockout (LSKO) and liver-specific Gab1 knockout (LGKO) mice displayed very similar phenotypes of defective liver regeneration triggered by PH, including blunted extracellular signalregulated kinase 1/2 (Erk1/2) activation, decreased expression of immediate-early genes, and reduced levels of cyclins A, E, and B1, as well as suppression of hepatocyte proliferation. In contrast, the Akt and interleukin-6/Stat3 pathways were up-regulated posthepatectomy in LSKO and LGKO mice, accompanied by improved hepatoprotection. Collectively, this study establishes the physiological significance of the Gab1/Shp2 link in promoting mitogenic signaling through the Erk pathway in mammalian liver regeneration.

In recent decades, N-heterocyclic carbenes have become established as a prevalent family of organocatalysts. N-Heterocyclic olefins, the alkylidene derivatives of N-heterocyclic carbenes, have recently also emerged as efficient promoters for CO2 fixation and polymerization reactions. Their extraordinarily strong Lewis/Brønsted basicity suggests great potential as a new class of organocatalysts for a broad range of reactions in synthetic chemistry.

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