Cu(II)-promoted methanolysis of N,N-dipicolylacetamide. multistep activation by decoupling of > ̈̈N-C═O resonance via Cu(II)-N binding, delivery of the Cu(II):((-)OCH3) nucleophile, and metal ion assistance of the departure of the leaving group

The methanolysis of the Cu(II) complex of N-acetyl-N,N-bis(2-picolyl)amine (2) was investigated by a kinetic study as a function of pH in methanol at 25 °C and computationally by DFT calculations. The active species is the basic form of the complex (3(-)), or (1:Cu(II))((-)OCH(3))(HOCH(3))), and the rate constant for its solvolysis is k(max) = 1.5 × 10(-4) s(-1). The mechanism involves Cu(II) binding to the amide N lone pair, decoupling it from >N-C═O resonance, concomitant with Cu(II):((-)OCH(3)) delivery to the adjacent >N-C═O unit, followed by Cu(II)-assisted departure of the N,N-bis(2-picolyl)amide from a tetrahedral intermediate.     

Systems biology and systems chemistry: new directions for drug discovery

Improvements in drug design have historically been centered around structure-based optimization of molecule specificity for a targeted protein, in an effort to reduce unintentional binding to other proteins and off-target effects. Although the "one-to-one" drug design strategy has been successful in impairing function of targets associated with a number of diseases, recent reports of drug promiscuity, which are a potential source of adverse reactions in patients, make a case to refine the drug design strategy such that it includes an awareness of multiple interactions from both ligand and protein perspectives. Polypharmacology and chemical biology studies are amassing interaction data at rapid rates, and the integration of such data into an interpretable model requires zooming our perspective out from the single ligand-target level to the larger network-wide level. We review some of the recent developments in systems-level research for drug design and discovery, and discuss the directions that some drug design efforts are heading toward.     

Pulsed hydrogen/deuterium exchange mass spectrometry for time‐resolved membrane protein folding studies

Kinetic folding experiments by pulsed hydrogen/deuterium exchange (HDX) mass spectrometry (MS) are a well‐established tool for water‐soluble proteins. To the best of our knowledge, the current study is the first that applies this approach to an integral membrane protein. The native state of bacteriorhodopsin (BR) comprises seven transmembrane helices and a covalently bound retinal cofactor. BR exposure to sodium dodecyl sulfate (SDS) induces partial unfolding and retinal loss. We employ a custom‐built three‐stage mixing device for pulsed‐HDX/MS investigations of BR refolding. The reaction is triggered by mixing SDS‐denatured protein with bicelles. After a variable folding time (10 ms to 24 h), the protein is exposed to excess D₂O buffer under rapid exchange conditions. The HDX pulse is terminated by acid quenching after 24 ms. Subsequent off‐line analysis is performed by size exclusion chromatography and electrospray MS. These measurements yield the number of protected backbone N–H sites as a function of folding time, reflecting the recovery of secondary structure. Our results indicate that much of the BR secondary structure is formed quite late during the reaction, on a time scale of 10 s and beyond. It is hoped that in the future it will be possible to extend the pulsed‐HDX/MS approach employed here to membrane proteins other than BR. Copyright © 2012 John Wiley & Sons, Ltd.     

Recent performance improvements to the DFT and TDDFT in GAMESS

The general atomic and molecular electronic structure system (GAMESS) is a quantum chemistry package used in the first-principles modeling of complex molecular systems using density functional theory (DFT) as well as a number of other post-Hartree-Fock methods. Both DFT and time-dependent DFT (TDDFT) are of particular interest to the materials modeling community. Millions of CPU hours per year are expended by GAMESS calculations on high-performance computing systems; any substantial reduction in the time-to-solution for these calculations represents a significant saving in CPU hours. As part of this work, three areas for improvement were identified: (1) the exchange-correlation (XC) integration grid, (2) profiling and optimization of the DFT code, and (3) TDDFT parallelization. We summarize the work performed in these task areas and present the resulting performance improvement. These software enhancements are available in 12JAN2009R3 or later versions of GAMESS.     

Modal analysis of the range evolution of broadband wavefields in the North Pacific Ocean: low mode numbers

The results of mode-processing measurements of broadband acoustic wavefields made in the fall of 2004 as part of the Long-Range Ocean Acoustic Propagation Experiment (LOAPEX) in the eastern North Pacific Ocean are reported here. Transient wavefields in the 50-90 Hz band that were recorded on a 1400-m long 40 element vertical array centered near the sound channel axis are analyzed. This array was designed to resolve low-order modes. The wavefields were excited by a ship-suspended source at seven ranges, between approximately 50 and 3200 km, from the receiving array. The range evolution of broadband modal arrival patterns corresponding to fixed mode numbers ("modal group arrivals") is analyzed with an emphasis on the second (variance) and third (skewness) moments. A theory of modal group time spreads is described, emphasizing complexities associated with energy scattering among low-order modes. The temporal structure of measured modal group arrivals is compared to theoretical predictions and numerical simulations. Theory, simulations, and observations generally agree. In cases where disagreement is observed, the reasons for the disagreement are discussed in terms of the underlying physical processes and data limitations.     

Unsupported lead clusters and electron diffraction

A beam of Pb clusters is produced with the inert gas aggregation method and probed by electron diffraction. Analysis of the diffraction patterns indicates that average cluster size can vary between 3 and 7 nm, according to nucleation conditions. The diffraction patterns from beams with larger average cluster size are very similar to patterns calculated from model decahedron clusters, while those for smaller cluster size do not appear to have simple geometrical face-centred cubic, decahedral, or icosahedral structure. Received 30 November 2000     

Spectral imaging system for non-contact colour measurement

This paper describes the development of a non-contact system for measuring colour of printed material at web speeds. The system proposed uses a non-contact spectrophotometer based on a holographic grating, in conjunction with a conventional monochrome area scan camera, from which colour spectral data is extracted, whilst a xenon flash is used to illuminate colour samples. Software and hardware details of the system are given, along with the underlying mathematics for colour space conversion and measurement. Conversion equations from X, Y, Z chromaticity co-ordinates to the RGB system are presented, and also equations to convert from the L^*a^*b^* colour space to X, Y, Z chromaticity co-ordinates. Experimental results are presented whereby the non-contact spectral system is shown to perform to a colour tolerance exceeding that of conventional colour video systems.     

New evidence for a subshell gap at N=32

An 879.9(2) keV γ-ray transition has been identified following the β decay of ⁵⁸V and assigned as the 2⁺₁→0⁺₁ transition in ⁵⁸Cr₃₄. A peak in the energies of the first excited 2⁺ states for the even–even chromium isotopes is now evident at ⁵⁶Cr₃₂, providing empirical evidence for a significant subshell gap at N=32. The appearance of this neutron subshell closure for neutron-rich nuclides may be attributed to the diminished π1f_7/2–ν1f_5/2 monopole proton–neutron interaction as protons are removed from the 1f_7/2 single-particle orbital.     

Singer's Formant in Sopranos: Fact or Fiction?

Although it is generally agreed that the singer's formant (F_S) is a prerequisite for successful stage performance, the results of this research do not support its presence in the soprano voices of trained female singers. Results are based on a recent investigation testing 10 advanced/professional sopranos in two groups singing sustained vowels at three frequencies: high (932 Hz), mid (622 Hz), and low (261 Hz). Spectrographic analysis shows that the nature of harmonic energy varies in relation to pitch. A resonance band somewhat resembling the tenor F_S was usually evident in vowels sung at low and mid pitch. However, unlike the F_S of typically less than 1 kHz bandwidth associated with tenors, sopranos singing similar pitches produced corresponding bandwidths which were significantly broader, usually at least 2-kHz wide. Vowels sung by sopranos at high-pitch levels exhibited strong fundamental frequency production with strong reinforcement of adjacent harmonics extending to 5 kHz and beyond. This type of production in essence nullifies the necessity for a typical F_S. Absence of the F_S in strong soprano voices might also imply the adaptation of a sufficiently different overall vocal tract configuration, so that techniques geared to developing maximal projection should not be the same as those developed to maximize the F_S in other voices.