A series of methylated and octylated pyridinium and quinolinium containing thiourea salts with a chiral 2-indanol substituent are reported. These organocatalysts are positively charged analogues of ...privileged bis(3,5-trifluoromethyl)phenyl substituted thioureas, and are found to be much more active catalysts despite the absence of an additional hydrogen bond donor or acceptor site (i.e., the presence of a heteroatom–hydrogen or heteroatom). Friedel–Crafts reactions of trans-β-nitorostyrenes with indoles are examined, and good yields and enantioselectivities are obtained. Mechanistic studies indicate that this is a second-order transformation under the employed conditions, and is consistent with the dimer of the thiourea being the active catalyst. Charged organocatalysts, consequently, represent an attractive design strategy for catalyst development.
Preferred protonation: Does electrospray ionization mass spectrometry produce gas-phase or liquid-phase structures? The preferred protonation site in p-aminobenzoic acid depends upon the medium, and ...the structure of its conjugate acid varies with the solvent used during spraying.
Ion channels represent the molecular entities that give rise to the cardiac action potential, the fundamental cellular electrical event in the heart. The concerted function of these channels leads to ...normal cyclical excitation and resultant contraction of cardiac muscle. Research into cardiac ion channel regulation and mutations that underlie disease pathogenesis has greatly enhanced our knowledge of the causes and clinical management of cardiac arrhythmia. Here we review the molecular determinants, pathogenesis, and pharmacology of congenital Long QT Syndrome. We examine mechanisms of dysfunction associated with three critical cardiac currents that comprise the majority of congenital Long QT Syndrome cases: 1) I
, the slow delayed rectifier current; 2) I
, the rapid delayed rectifier current; and 3) I
, the voltage-dependent sodium current. Less common subtypes of congenital Long QT Syndrome affect other cardiac ionic currents that contribute to the dynamic nature of cardiac electrophysiology. Through the study of mutations that cause congenital Long QT Syndrome, the scientific community has advanced understanding of ion channel structure-function relationships, physiology, and pharmacological response to clinically employed and experimental pharmacological agents. Our understanding of congenital Long QT Syndrome continues to evolve rapidly and with great benefits: genotype-driven clinical management of the disease has improved patient care as precision medicine becomes even more a reality.
The coronavirus disease 2019 pandemic has greatly increased the frequency of disinfecting surfaces in public places, causing a strain on the ability to obtain disinfectant solutions. An alternative ...is to use plain alcohols (EtOH and IPA) or sodium hypochlorite (SH).
To determine the efficacy of various concentrations of EtOH, IPA and SH on a human coronavirus (HCoV) dried on to surfaces using short contact times.
High concentrations of infectious HCoV were dried on to porcelain and ceramic tiles, then treated with various concentrations of the alcohols for contact times of 15 s, 30 s and 1 min. Three concentrations of SH were also tested. Reductions in titres were measured using the tissue culture infectious dose 50 assay.
Concentrations of EtOH and IPA from 62% to 80% were very efficient at inactivating high concentrations of HCoV dried on to tile surfaces, even with a 15-s contact time. Concentrations of 95% dehydrated the virus, allowing infectious virus to survive. The dilutions of SH recommended by the Centers for Disease Control and Prevention (1/10 and 1/50) were efficient at inactivating high concentrations of HCoV dried on to tile surfaces, whereas a 1/100 dilution had substantially lower activity.
Multiple concentrations of EtOH, IPA and SH efficiently inactivated infectious HCoV on hard surfaces, typical of those found in public places. Often no remaining infectious HCoV could be detected.
Cycloadditions of epoxides with CO2 to synthesize cyclic five-membered ring organic carbonates are of broad interest from a synthetic, environmental, and green chemistry perspective, and the ...development of effective catalysts for these transformations is an ongoing challenge. A series of eight charge-containing thiourea salts that catalyze these reactions under mild conditions (i.e., 60 °C and atmospheric CO2 pressure) are reported. Substrate scope and mechanistic studies were also carried out, isotope effects were measured, and a reactive intermediate was isolated revealing a surprising pathway in which a thiourea catalyst serves as a nucleophile in the cleavage of the epoxide ring.
Infrared photodissociation (IRPD) spectra are reported for a proline–chloride anion cluster along with its d 2- and d 7-isotopomers. The spectral data indicate that proline is in its neutral form as ...opposed to a zwitterion, and computations are in agreement in that some neutral conformers are energetically low-lying and reproduce the observed spectra. Zwitterionic conformers are predicted to be essentially as stable as the neutral ones and should be significantly populated; however, there is no evidence for these structures in the IRPD spectra. An exploration of the potential energy surface for the loss of chloride anion, the observed fragmentation channel, reveals that it is 8.4 kcal mol–1 more difficult to break apart the zwitterionic cluster ion. This is a reflection of the 15.8 kcal mol–1 estimate for the gaseous proline zwitterion–neutral energy difference. Kinetic results suggest the presence of two photolabile populations in similar amounts (i.e., 56 vs 44%). The more abundant structure is also the more labile species, and the neutral form of proline is assigned to this cluster ion. The less abundant and slower fragmenting structure consequently is zwitterionic. As originally suggested by Evans et al. in general, it appears that in this instance both spectral and kinetic data are needed to determine the structure of the proline–chloride anion cluster.
The population vector (PV) algorithm and optimal linear estimation (OLE) have been used to reconstruct movement by combining signals from multiple neurons in the motor cortex. While these linear ...methods are effective, recursive Bayesian decoding schemes, which are nonlinear, can be more powerful when probability model assumptions are satisfied. We have implemented a recursive Bayesian algorithm for reconstructing hand movement from neurons in the motor cortex. The algorithm uses a recently developed numerical method known as "particle filtering" and follows the same general strategy as that used by Brown et al. to reconstruct the path of a foraging rat from hippocampal place cells. We investigated the method in a numerical simulation study in which neural firing rate was assumed to be positive, but otherwise a linear function of movement velocity, and preferred directions were not uniformly distributed. In terms of mean-squared error, the approach was approximately 10 times more efficient than the PV algorithm and 5 times more efficient than OLE. Thus use of recursive Bayesian decoding can achieve the accuracy of the PV algorithm (or OLE) with approximately 10 times (or 5 times) fewer neurons. The method was also used to reconstruct hand movement in an ellipse-drawing task from 258 cells in the ventral premotor cortex. Recursive Bayesian decoding was again more efficient than the PV and OLE methods, by factors of roughly seven and three, respectively.
Acidities are commonly measured in polar solvents but catalytic reactions are typically carried out in nonpolar media. IR spectra of a series of phenols in CCl4 and 1% CD3CN/CCl4 provide relative ...acidities. Nonprotonated charged substituents with an appropriate counterion are found to enhance their Brønsted acidities and improve catalyst performance by orders of magnitude.
Infrared multiphoton dissociation spectra of protonated p-aminobenzoic acid generated by electrospray ionization (ESI) from aqueous methanol and acetonitrile solutions were recorded in the gas phase ...from 2800–4000 cm–1. The O-protonated ion is more stable than the N-protonated structure in the gas phase, whereas the opposite is true in both solutions. When CH3OH/H2O was used as the ESI solvent, only the O-protonated ion was observed. In contrast, a 70:30 mixture of the O- and N-protonated species were produced from CH3CN/H2O. These structural assignments are based on an assortment of experimental data (action spectra, photofragments, photofragmentation kinetics, and H/D exchange) and are fully supported by extensive computations. This work shows that ESI can lead to isomerization and that the ionization site may be varied by changing the solvent from which the substrate is analyzed.
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