Oxygen (O(2)) is a prerequisite for cellular respiration in aerobic organisms but also elicits toxicity. To understand how animals cope with the ambivalent physiological nature of O(2), it is critical to elucidate the molecular mechanisms responsible for O(2) sensing. Here our systematic evaluation of transient receptor potential (TRP) cation channels using reactive disulfides with different redox potentials reveals the capability of TRPA1 to sense O(2). O(2) sensing is based upon disparate processes: whereas prolyl hydroxylases (PHDs) exert O(2)-dependent inhibition on TRPA1 activity in normoxia, direct O(2) action overrides the inhibition via the prominent sensitivity of TRPA1 to cysteine-mediated oxidation in hyperoxia. Unexpectedly, TRPA1 is activated through relief from the same PHD-mediated inhibition in hypoxia. In mice, disruption of the Trpa1 gene abolishes hyperoxia- and hypoxia-induced cationic currents in vagal and sensory neurons and thereby impedes enhancement of in vivo vagal discharges induced by hyperoxia and hypoxia. The results suggest a new O(2)-sensing mechanism mediated by TRPA1.
Asymmetric reaction of dimethylzinc and benzaldehyde in the presence of (2S)-3-exo-(dimethylamino)isoborneol [(2S)-DAIB] exhibits unusual nonlinear phenomena. The enantiomeric purity of the product
is much higher than that of the chiral source, DAIB, while the rate of the enantioselective catalysis decreases
considerably as the enantiomeric excess (ee) of DAIB is lowered. Such effects originate from the reversible
homochiral and heterochiral interaction of the coexistent enantiomeric zinc amino alkoxide catalysts which
are formed from dimethylzinc and (2S)- and (2R)-DAIB. The thermodynamics of the five-component
equilibration between the two monomers and three dimers, when coupled with the kinetics of the alkylation,
strongly affects the extent of enantioselectivity and the reaction rate of the alkylation reaction. The overall
profile of the nonlinear effects has been clarified mathematically using experimentally available parameters,
viz., the equilibrium constants of the dimer/monomer conversion and the association of the monomeric catalyst
with the organozinc and aldehyde, the rate constant of alkyl transfer from the catalyst/dimethylzinc/aldehyde
mixed complex, the ee of DAIB, and the concentrations of DAIB, dimethylzinc, and aldehyde. 3D graphics
are presented for the correlation of the enantiomeric purity of the product with DAIB ee and the concentrations
of dimethylzinc and aldehyde and for the relationship between the reaction rate, DAIB ee, and the concentrations
of the organozinc and aldehyde. The computer simulation is in good agreement with the experimental results,
confirming that the nonlinear effects result from the competition of two enantiomorphic catalytic cycles involving
the monomeric chiral zinc catalysts rather than the diastereomorphic catalytic cycles with dinuclear zinc catalysts.
Furthermore, this study indicates that the degree of nonlinear effects in asymmetric catalysis could be affected
not only by the catalyst ee but also by various reaction parameters, particularly the concentrations of the
catalyst, reagent, and substrate as well as the extent of conversion.
We have developed a method that involves the generation of a “cation pool” using low-temperature
electrolysis, and then its reaction with nucleophiles under non-oxidative conditions. This one-pot method solves
problems associated with conventional oxidative generation of cations and their in situ reaction with nucleophiles,
and provides an efficient method for direct oxidative carbon−carbon bond formation. As an example of this
method, generation of cation pools from carbamates by low-temperature electrolysis (−72 °C) and their reactions
with carbon nucleophiles such as allylsilanes, enol silyl ethers, and enol acetates were examined and the desired
products were obtained in good yields. Aromatic compounds and 1,3-dicarbonyl compounds can also be utilized
as carbon nucleophiles. The present method was also applied to combinatorial parallel synthesis using a robotic
synthesizer.
ContentsCover: Interdigital Micromixer HPIMM for high pressure and high temperature applications. With Courtesy of Institut für Mikrotechnik Mainz GmbH, Germany.
Editorial:From Review: Efficient micromixing possible with a short diffusion path increases the product selectivity of competitive parallel reactions and competitive consecutive reactions. This concept has been expanded to control the molecular weight and molecular weight distribution in carbocationic polymerization. The efficient heat transfer, based on high surface to volume ratios, allows precise temperature control and is also effective for the control of highly exothermic reactions, such as free radical polymerization. Review: Microstructured reactors have the potential to change industrial chemical production. The main arguments for using microstructured reactors are enhanced conversion and selectivity, increased spacetime yields, waste reduction, and better safety given by the small reactor volumes. Credit-card sized reaction systems allow to perform the screening of multi-step reactions in one run. This essay focuses on the grouping and benchmarking of current works and the evaluation and direct comparison to established technology.
Organic Synthesis with Microstructured Reactors
Current events: Nanowires of the organic semiconductor copper–tetracyanoquinodimethane (Cu–TCNQ) have been synthesized in a controlled manner and patterned on a variety of substrates by chemical vapor deposition. A cross‐point memory device based on a network of Cu–TCNQ nanowires (see picture) has been constructed that repeatedly switches electrically between two states with a conductivity difference of more than two orders of magnitude.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.