JE-TROSY: combined J- and TROSY-spectroscopy for the measurement of one-bond couplings in macromolecules

With the application of RDCs in high-resolution NMR studies of macromolecules, there has been an interest in the development of accurate, sensitive methods for measuring 15N-1H and 13C-1H one-bond coupling constants. Most methods for determining these couplings are based on the measurement of the displacement between cross-peak components in J-coupled spectra. However, for large macromolecules and macromolecular complexes, these methods are often unreliable since differential relaxation can significantly broaden one of the multiplet components (i.e., the anti-TROSY component) and thereby make accurate determination of its position difficult. To overcome this problem, a J-evolved transverse relaxation optimized (JE-TROSY) method is presented for the determination of one-bond couplings that involves J-evolution of the sharpest cross-peak multiplet component selected in a TROSY experiment. Couplings are measured from the displacement of the TROSY component in the additional J-evolution dimension relative to a zero frequency origin. The JE-TROSY method is demonstrated on uniformly labeled 15N, 13C-labeled RNA and peptide samples, as well as with an RNA-protein complex, in which the protein is uniformly 15N, 13C-labeled. In all cases, resolved, sensitive spectra are obtained from which heteronuclear one-bond J-couplings could be accurately and easily measured.     

Insights into brain microstructure from the T2 distribution

T2 weighting is particularly sensitive, but notoriously unspecific, to a wide range of brain pathologies. However, careful measurement and analysis of the T2 decay curve from brain tissue promise to provide much improved pathological specificity. In vivo T2 measurement requires accurate 180 pulses and appropriate manipulation of stimulated echoes; the most common approach is to acquire multiple echoes from a single slice. The T2 distribution, a plot of component amplitude as a function of T2, can be estimated using an algorithm capable of fitting a multi-exponential T2 decay with no a priori assumptions about the number of exponential components. T2 distributions from normal brain show peaks from myelin water, intra/extracellular water and cerebral spinal fluid; they can be used to provide estimates of total water content (total area under the T2 distribution) and myelin water fraction (MWF, fractional area under the myelin water peak), a measure believed to be related to myelin content. Experiments on bovine brain suggest that magnetization exchange between water pools plays a minor role in the T2 distribution. Different white matter structures have different MWFs. In normal white matter (NWM), MWF is not correlated with the magnetization transfer ratio (MTR) or the diffusion tensor fractional anisotropy (FA); hence it provides unique information about brain microstructure. Normal-appearing white matter (NAWM) in multiple sclerosis (MS) brain possesses a higher water content and lower MWF than controls, consistent with histopathological findings. Multiple sclerosis lesions demonstrate great heterogeneity in MWF, presumably due to varying myelin contents of these focal regions of pathology. Subjects with schizophrenia were found to have significantly reduced MWF in the minor forceps and genu of the corpus callosum when compared to controls, suggesting that reduced frontal lobe myelination plays a role in schizophrenia. In normal controls, frontal lobe myelination was positively correlated with both age and education; this result was not observed in subjects with schizophrenia. A strong correlation between MWF and the optical density from the luxol fast blue histological stain for myelin was observed in formalin-fixed brain, supporting the use of the MWF as an in vivo myelin marker.     

Towards Photochromic Azobenzene-Based Inhibitors for Tryptophan Synthase

Light regulation of drug molecules has gained growing interest in biochemical and pharmacological research in recent years. In addition, a serious need for novel molecular targets of antibiotics has emerged presently. Herein, the development of a photocontrollable, azobenzene-based antibiotic precursor towards tryptophan synthase (TS), an essential metabolic multienzyme complex in bacteria, is presented. The compound exhibited moderately strong inhibition of TS in its E configuration and five times lower inhibition strength in its Z configuration. A combination of biochemical, crystallographic, and computational analyses was used to characterize the inhibition mode of this compound. Remarkably, binding of the inhibitor to a hitherto-unconsidered cavity results in an unproductive conformation of TS leading to noncompetitive inhibition of tryptophan production. In conclusion, we created a promising lead compound for combatting bacterial diseases, which targets an essential metabolic enzyme, and whose inhibition strength can be controlled with light.     

CRYSTAL STRUCTURE AND MORPHOLOGY OF NASCENT SAMPLES OF SYMMETRIC AROMATIC POLYESTERS——Ⅱ. POLY(p-PHENYLENE 2,6-NAPHTHALATE)

Confined thin film melt polymerization (CTFMP) of naphthalene chloride/hydroquinone (NCMQ, 1/1, molar)mixtures at polymerization temperatures (T_p) below ca. 300℃ resulted in relatively thick, elongated crystals. Polymerizationof NC/HQ above 300℃ between glass yielded well-formed lamellar crystals ca. 100 A thick. Phase Ⅰ and Ⅱ [001] EDpatterns were obtained for all T_p, the relative amount of phase Ⅰ increasing with T_p. Polymerization of naphthalenedicarboxylic acid/hydroquinione diacetate 1/1 mixtures at high T_p also yielded lamellar crystals that "curled up" off of thesubstrate. When the high temperature CTFMP polymerization was conducted between mica, aggregates of lamellae on-edgedeveloped but epitaxial growth did not occur. Epitaxial growth of lamellae between mica could be obtained, however, byconfined thin film solution polymerization, with both of the latter samples yielding apparently related ED patterns from adifferent unit cell than phase Ⅰ or Ⅱ. Fiber patterns, obtained from sheared samples, indicated considerably greater crystaldisorder than in the nascent crystals. Refinement of the phase Ⅰ unit cell parameters, based on the [001] and [01 1] EDpatterns, with modeling based on Cerius~2, suggests a monoclinic phase Ⅰ unit cell with a = 7.76, b = 5.71, c = 14.99 A, α = γ= 90°, β= 99.7°, ρ = 1.47 g/cm~3, space group P12_1/al.     

α-SUBSTITUIERTE PHOSPHONATE 52.1 SYNTHESE UND REAKTIONEN VON 1- ACETOXY-1-METHYLTHIOMETHAN PHOSPHORYLVERBINDUNGEN

Abstract

The 1-acetoxy-1-methylthiomethanephosphoryl compounds (4) are prepared from methylthiomethanephosphoryl derivatives (1) by electrolysis in 0.6 molar sodium acetate/acetic acid solution. The reaction of 1-acetoxy compounds (4) with halogen carriers gives the 1-halogen-1-methylthiomethane-phosphoryl derivatives 5, 7 and 8. The reaction of 4a under PTC-conditions results in cleavage of the P-C-bond.

Die 1-Acetoxy-1-methylthiomethanphosphoryl-Verbindungen (4) wurden aus Methylthiomethanphos-phorylderivaten (1) durch Elektrolyse in 0.6 molarer Na-acetat/Essigsäure-Lösung dargestellt. Die Reaktion der 1-Acetoxyverbindungen mit Halogenüberträgern führt zu den 1-Halogen-1-methyl-thiomethanphosphorylderivaten 5, 7 und 8. Bei Reaktion von 4a unter PTC-Bedingungen beobachtet man eine Spaltung der P-C-Bindung.     

WavePacket: A Matlab package for numerical quantum dynamics. III. Quantum-classical simulations and surface hopping trajectories

WavePacket is an open-source program package for numerical simulations in quantum dynamics. Building on the previous Part I (Schmidt and Lorenz, Comput. Phys. Commun. 2017, 213, 223] and Part II (Schmidt and Hartmann, Comput. Phys. Commun. 2018, 228, 229] which dealt with quantum dynamics of closed and open systems, respectively, the present Part III adds fully classical and mixed quantum-classical propagation techniques to WavePacket. There classical phase-space densities are sampled by trajectories which follow (diabatic or adiabatic) potential energy surfaces. In the vicinity of (genuine or avoided) intersections of those surfaces, trajectories may switch between them. To model these transitions, two classes of stochastic algorithms have been implemented: (1) Tully's fewest switches surface hopping and (2) Landau–Zener-based single switch surface hopping. The latter one offers the advantage of being based on adiabatic energy gaps only, thus not requiring nonadiabatic coupling information any more. The present work describes the MATLAB version of WavePacket 6.1.0, which is essentially an object-oriented rewrite of previous versions, allowing to perform fully classical, quantum-classical and quantum-mechanical simulations on an equal footing, that is, for the same physical system described by the same WavePacket input. The software package is hosted and further developed at the Sourceforge platform, where also extensive Wiki-documentation as well as numerous worked-out demonstration examples with animated graphics are available. © 2019 Wiley Periodicals, Inc.