Evidence for micellar structure in the gas phase

We have compared micelles, reverse micelles, and reverse micelles encapsulating myoglobin using electrospray mass spectrometry. To enable a direct comparison, the same surfactant (cetyltrimethylammonium bromide (CTAB)) was used in each case and micelle formation was controlled by manipulating the aqueous and organic phases. Tandem mass spectra of the resulting micelle preparations reveal differences in the ions that dissociate: those that dissociate from regular micelles have undergone >90% exchange of bromide ions from the headgroup with acetate ions from bulk solvent. By contrast, for reverse micelles, ions are detected without exchange of bromide ions from the headgroup, consistent with their protection in the core of the micellar structure. Tandem mass spectra of micelles and reverse micelles reveal polydispersed assemblies containing several hundred CTAB molecules, indicating the coalescence of the micellar systems to form large assemblies. For reverse micelles incorporating myoglobin, spectra are consistent with one holo myogolobin molecule in association with approximately 270 CTAB molecules. Overall, therefore, our results show that the solution-phase orientation of surfactants is preserved during electrospray and are consistent with interactions being maintained between surfactants and an encapsulated protein.     

Asymmetric total synthesis of nigerone

[reaction: see text] An enantioselective synthesis of the chiral bisnaphthopyrone natural product nigerone is reported. The key step was an eight-step isomerization process to form the final natural product. The isomerization precursor was constructed via asymmetric oxidative biaryl coupling of an advanced intermediate with a 1,5-diaza-cis-decalin copper catalyst.     

A combinatorial approach to studying protein complex composition by employing size-exclusion chromatography and proteome analysis

The genome sequences of numerous organisms are available now, but gene sequences alone do not provide sufficient information to accurately deduce protein functions. Protein function is largely dependent on the association of multiple polypeptide chains into large structures with interacting subunits that regulate and support each other. Therefore, the mapping of protein interaction networks in a physiological context is conducive to deciphering protein functions, including those of hypothetical proteins. Although several high-throughput methods to globally identify protein interactions have been reported in recent years, these approaches often have a high rate of nonspecific or artificial interactions detected. For instance, the fraction of false positives of the protein interactions identified by yeast two-hybrid assay has been predicted to be of the order of 50%. We have developed a strategy to globally map Bacillus subtilis protein-protein interactions in a physiological context by fractionating the cell lysates using size-exclusion chromatography (SEC), followed by proteome analysis. Components of both known and unknown protein complexes, multisubunits and multiproteins, have been identified using this strategy. In one case, the partners of the B. subtilis protein complex have been coexpressed in Escherichia coli, and the formation of the overexpressed protein complex has been further confirmed by a pull-down assay.     

Speech enhancement using the modified phase-opponency model

In this paper we present a model called the Modified Phase-Opponency (MPO) model for single-channel speech enhancement when the speech is corrupted by additive noise. The MPO model is based on the auditory PO model, proposed for detection of tones in noise. The PO model includes a physiologically realistic mechanism for processing the information in neural discharge times and exploits the frequency-dependent phase properties of the tuned filters in the auditory periphery by using a cross-auditory-nerve-fiber coincidence detection for extracting temporal cues. The MPO model alters the components of the PO model such that the basic functionality of the PO model is maintained but the properties of the model can be analyzed and modified independently. The MPO-based speech enhancement scheme does not need to estimate the noise characteristics nor does it assume that the noise satisfies any statistical model. The MPO technique leads to the lowest value of the LPC-based objective measures and the highest value of the perceptual evaluation of speech quality measure compared to other methods when the speech signals are corrupted by fluctuating noise. Combining the MPO speech enhancement technique with our aperiodicity, periodicity, and pitch detector further improves its performance.     

Synthesis of Phenyl or 4-Nitrophenyl Methyl β-Ketophosphonate Esters

Seven new aryl methyl g -ketophosphonate esters were synthesized. The hydrolytic rates of the compounds under physiological conditions were studied. Most of the compounds are effective inhibitors of acetylcholinesterase. The enzyme recovers on the 10-50 h time scale from its adducts with two of the inhibitors.     

Practical application of 1H benchtop NMR spectroscopy for the characterization of a nonaqueous phase liquid from a contaminated environment

Nonaqueous phase liquids (NAPLs) located at the surface of the water table and/or below the water table are often a significant source for groundwater contamination near current or former commercial/industrial facilities. Due to the complex and long history of many industrial sites, these NAPLs often contain a complex mixture of contaminants and as such can be difficult to fully characterize using conventional analytical methods. Remediation and risk assessment activities at sites containing NAPLs may, subsequently, be hindered as the contamination profile may not be fully understood. This paper demonstrates the application of bench-scale ¹H nuclear magnetic resonance (NMR) spectroscopy as a practical tool to assist with the characterization of complex NAPLs. Here, a NAPL collected from a contaminated site situated near a former chemical manufacturing facility was analyzed using a combination of one-dimensional (1D) ¹H NMR spectroscopy and two-dimensional (2D) ¹H J-resolved spectroscopy (JRES). It is shown that 1D NMR experiments are useful in the rapid identification of the classes of compounds present, whereas 2D JRES NMR experiments are useful in identifying specific compounds. The use of benchtop NMR spectroscopy as a simple and cost effective tool to assist in the analysis of contaminated sites may help improve the practical characterization of many heavily contaminated sites and facilitate improved risk assessments and remedial strategies.     

The Role of Lateral Tension in Calcium-Induced DPPS Vesicle Rupture

We assess the role of lateral tension in rupturing anionic dipalmitoylphosphatidyserine (DPPS), neutral dipalmitoylphosphatidylcholine (DPPC), and mixed DPPS-DPPC vesicles. Binding of Ca(2+) is known to have a significant impact on the effective size of DPPS lipids and little effect on the size of DPPC lipids in bilayer structures. In the present work we utilized laser transmission spectroscopy (LTS) to assess the effect of Ca(2+)-induced stress on the stability of the DPPS and DPPC vesicles. The high sensitivity and resolution of LTS has permitted the determination of the size and shape of liposomes in solution. The results indicate a critical size after which DPPS single shell vesicles are no longer stable. Our measurements indicate Ca(2+) promotes bilayer fusion up to a maximum diameter of ca. 320 nm. These observations are consistent with a straightforward free-energy-based model of vesicle rupture involving lateral tension between lipids regulated by the binding of Ca(2+). Our results support a critical role of lateral interactions within lipid bilayers for controlling such processes as the formation of supported bilayer membranes and pore formation in vesicle fusion. Using this free energy model we are able to infer a lower bound for the area dilation modulus for DPPS (252 pN/nm) and demonstrate a substantial free energy increase associated with vesicle rupture.     

The interaction of the antitoxin DM43 with a snake venom metalloproteinase analyzed by mass spectrometry and surface plasmon resonance

DM43 is a circulating dimeric antitoxin isolated from Didelphis aurita, a South American marsupial naturally immune to snake envenomation. This endogenous inhibitor binds non‐covalently to jararhagin, the main hemorrhagic metalloproteinase from Bothrops jararaca snake venom, and efficiently neutralizes its toxicity. The aim of this study was to apply mass spectrometry (MS) and surface plasmon resonance (SPR) to improve the molecular characterization of this heterocomplex. The stoichiometry of the interaction was confirmed by nanoelectrospray ionization‐quadrupole‐time‐of‐flight MS; from native solution conditions, the complex showed a molecular mass of ~94 kDa, indicating that one molecule of jararhagin (50 kDa) interacts with one monomer of DM43 (43 kDa). Although readily observed in solution, the dimeric structure of the inhibitor was barely preserved in the gas phase. This result suggests that, in contrast to the toxin–antitoxin complex, hydrophobic interactions are the primary driving force for the inhibitor dimerization. For the real‐time interaction analysis, the toxin was captured on a sensor chip derivatized with the anti‐jararhagin monoclonal antibody MAJar 2. The sensorgrams obtained after successive injections of DM43 in a concentration series were globally fitted to a simple bimolecular interaction, yielding the following kinetic rates for the DM43/jararhagin interaction: k_a = 3.54 ± 0.03 × 10⁴ M^?1 s^?1 and k_d = 1.16 ± 0.07 × 10^?5 s^?1, resulting in an equilibrium dissociation constant (K_D) of 0.33 ± 0.06 nM. Taken together, MS and SPR results show that DM43 binds to its target toxin with high affinity and constitute the first accurate quantitative study on the extent of the interaction between a natural inhibitor and a metalloproteinase toxin, with unequivocal implications for the use of this kind of molecule as template for the rational development of novel antivenom therapies. Copyright © 2012 John Wiley & Sons, Ltd.     

量子化学的Gaussian-2理论及其应用与化合物的标准生成烩预测

本文较为全面地综述了Gaussian-1, Gaussian-2(简称G1,G2)理论以及简化的G2 CMP2 ) ,G2 (MP3)理论,将其主要结果进行了比较分析。关于G2理论的应用,除了较为详细地综述了几年来理论在重现实验数据、评价实验数据、预测实验数据及研究化学反应途径等方面的应用外,还结合我仁近期研究结果的主要结论讨论了该理论在研究等电子一等自旋,价层等电一等旋,等旋及非等旋化学反应的能量计算中的应用情况,以及该理论在预测化合物的标准生成蛤方面的应用情况。     

The dynamics of single chains within a model polymer melt

Discontinuous molecular dynamics simulations are performed on a system containing 32 hard chains of length 192 at a volume fraction of phi = 0.45 to explore the idea that localized entanglements have a significant effect on the dynamics of the individual chains within an entangled polymer melt. Anomalous behavior can still be observed when studying the dynamics of the individual chains, although increased time averaging causes the anomalous relaxation-memory-release behavior that was observed previously in the system to smooth out. First, the individual chain mean squared displacements and apparent diffusion coefficients are calculated, and a wide distribution of diffusive behavior is found. Although the apparent diffusion coefficient curve averaged over all chains displays the predicted long-time diffusive behavior, the curves for the individual chains differ both qualitatively and quantitatively. They display superdiffusive, diffusive, and subdiffusive behavior, with the largest percentage of chains exhibiting superdiffusive behavior and the smallest percentage exhibiting the predicted diffusive behavior. Next, the individual chain end-to-end vector autocorrelation functions and relaxation times are determined, and a wide distribution of stress relaxation behavior is found. The times when the end-to-end vector autocorrelation functions relax completely span almost an order of magnitude in reduced time. For some chains, the end-to-end vector autocorrelation function relaxes smoothly toward zero similar to the system average; however, for other chains the relaxation is slowed greatly, indicating the presence of additional entanglements. Almost half of the chains exhibit the anomalous behavior in the end-to-end vector autocorrelation function. Finally, the dynamic properties are displayed for a single chain exhibiting anomalous relaxation-memory-release behavior, supporting the idea that the relaxation-memory-release behavior is a single-chain property.