J. Appl. Cryst.の発刊に際して

Computational Prediction of 1H and 13C Chemical Shifts: A Useful Tool for Natural Product, Mechanistic, and Synthetic Organic Chemistry

Water and silicon are chemically dissimilar substances with common physical properties. Their liquids display a temperature of maximum density, increased diffusivity on compression, and they form tetrahedral crystals and tetrahedral amorphous phases. The common feature to water, silicon, and carbon is the formation of tetrahedrally coordinated units. We exploit these similarities to develop a coarse-grained model of water (mW) that is essentially an atom with tetrahedrality intermediate between carbon and silicon. mW mimics the hydrogen-bonded structure of water through the introduction of a nonbond angular dependent term that encourages tetrahedral configurations. The model departs from the prevailing paradigm in water modeling: the use of long-ranged forces (electrostatics) to produce short-ranged (hydrogen-bonded) structure. mW has only short-range interactions yet it reproduces the energetics, density and structure of liquid water, and its anomalies and phase transitions with comparable or better accu...

Water Modeled As an Intermediate Element between Carbon and Silicon

Oligomeric assemblies formed from a variety of disease-associated peptides and proteins have been strongly associated with toxicity in many neurodegenerative conditions, such as Alzheimer’s disease. The precise nature of the toxic agents, however, remains still to be established. We show that prefibrillar aggregates of E22G (arctic) variant of the Aβ1−42 peptide bind strongly to 1-anilinonaphthalene 8-sulfonate and that changes in this property correlate significantly with changes in its cytotoxicity. Moreover, we show that this phenomenon is common to other amyloid systems, such as wild-type Aβ1–42, the I59T variant of human lysozyme and an SH3 domain. These findings are consistent with a model in which the exposure of hydrophobic surfaces as a result of the aggregation of misfolded species is a crucial and common feature of these pathogenic species.

ANS binding reveals common features of cytotoxic amyloid species

In 2010 we energy-minimized 225 high-quality single-crystal (SX) structures with dispersion-corrected density functional theory (DFT-D) to establish a quantitative benchmark. For the current paper, 215 organic crystal structures determined from X-ray powder diffraction (XRPD) data and published in an IUCr journal were energy-minimized with DFT-D and compared to the SX benchmark. The on average slightly less accurate atomic coordinates of XRPD structures do lead to systematically higher root mean square Cartesian displacement (RMSCD) values upon energy minimization than for SX structures, but the RMSCD value is still a good indicator for the detection of structures that deserve a closer look. The upper RMSCD limit for a correct structure must be increased from 0.25 A for SX structures to 0.35 A for XRPD structures; the grey area must be extended from 0.30 to 0.40 A. Based on the energy minimizations, three structures are re-refined to give more precise atomic coordinates. For six structures our calculations provide the missing positions for the H atoms, for five structures they provide corrected positions for some H atoms. Seven crystal structures showed a minor error for a non-H atom. For five structures the energy minimizations suggest a higher space-group symmetry. For the 225 SX structures, the only deviations observed upon energy minimization were three minor H-atom related issues. Preferred orientation is the most important cause of problems. A preferred-orientation correction is the only correction where the experimental data are modified to fit the model. We conclude that molecular crystal structures determined from powder diffraction data that are published in IUCr journals are of high quality, with less than 4% containing an error in a non-H atom.

https://journals.iucr.org/b/issues/2014/06/00/kd5080/kd5080.pdf

Validation of molecular crystal structures from powder diffraction data with dispersion-corrected density functional theory (DFT-D).

A sequence of seven nematic phases has been observed in chiral mesogenic dimers, having odd number of carbon atoms in the spacer, thus a bent shape. The highest temperature phase is a chiral nematic (cholesteric) phase on heating or blue phases on cooling. The lowest temperature nematic phase expels the chiral twist and exhibits spontaneous bent–splay modulation.

/pdf/multiple-nematic-phases-observed-in-chiral-mesogenic-dimers-53zoatxbol.pdf

Multiple nematic phases observed in chiral mesogenic dimers

Signal amplification by reversible exchange (SABRE) can enhance nuclear magnetic resonance signals by several orders of magnitude. However, until now this was limited to a small number of model target molecules. Here, a new convenient method for SABRE activation applicable to a variety of synthetic model oligopeptides is demonstrated. For the first time, a highly SABRE-active pyridine-based biocompatible molecular framework is incorporated into synthetic oligopeptides. The SABRE activity is preserved, demonstrating the importance of such earmarking. Finally, a crucial exchange process responsible for SABRE activity is identified and discussed.

NMR Signal Enhancement by Effective SABRE Labeling of Oligopeptides

Liquid-phase NMR studies on hindered rotation of methyl group in a 9-methyltriptycene derivative are reported where the standard, classical jump model of the methyl dynamics proves inadequate. On the other hand, accurate reproduction of the observed NMR line shape effects is afforded by the use of a recent quantum mechanical model in which the relevant methyl dynamics are described in terms of two quantum rate (coherence-damping) processes, characterized by two different rate constants. For ambient temperatures, such a direct evidence of the quantum nature of a rate process generally believed to be classical seems to have no precedence in the literature.

Wave properties of a methyl group under ambient conditions.

Amyloid β, Aβ(1-42), is a component of senile plaques present in the brain of Alzheimer's disease patients and one of the main suspects responsible for pathological consequences of the disease. Herein, we directly visualize the Aβ activity toward a brain-like model membrane and demonstrate that this activity strongly depends on the Aβ oligomer size. PeakForce quantitative nanomechanical mapping mode of atomic force microscopy imaging revealed that the interaction of large-size (LS) Aβ oligomers, corresponding to high-molecular-weight Aβ oligomers, with the brain total lipid extract (BTLE) membrane resulted in accelerated Aβ fibrillogenesis on the membrane surface. Importantly, the fibrillogenesis did not affect integrity of the membrane. In contrast, small-size (SS) Aβ oligomers, corresponding to low-molecular-weight Aβ oligomers, created pores and then disintegrated the BTLE membrane. Both forms of the Aβ oligomers changed nanomechanical properties of the membrane by decreasing its Young's modulus by ∼45%. Our results demonstrated that both forms of Aβ oligomers induce the neurotoxic effect on the brain cells but their action toward the membrane differs significantly.

https://pubs.acs.org/doi/pdf/10.1021/acs.langmuir.9b01645

Size-Dependent Interaction of Amyloid β Oligomers with Brain Total Lipid Extract Bilayer-Fibrillation Versus Membrane Destruction.

The dynamics of strongly hindered methyl groups in 9-methyltriptycene derivatives, monitored by liquid-phase nuclear magnetic resonance spectra, were investigated using an iterative, least-squares method of line shape analysis. For two of the compounds, apart from nonclassical effects in the stochastic dynamics, anomalously strong dependence on temperature (ca. 0.05 and 0.08 Hz/K) of the J coupling between the methyl protons was observed. The latter effect was attributed to the occurrence of coherent quantum tunneling of the methyl rotor. For methyl group, this would be the first observation of coherent tunneling above cryogenic temperatures.

Piotr Bernatowicz

Papers

Multiple nematic phases observed in chiral mesogenic dimers

NMR Signal Enhancement by Effective SABRE Labeling of Oligopeptides

Wave properties of a methyl group under ambient conditions.

Size-Dependent Interaction of Amyloid β Oligomers with Brain Total Lipid Extract Bilayer-Fibrillation Versus Membrane Destruction.

Nonclassical effects in liquid-phase nuclear magnetic resonance spectra of 9-methyltriptycene derivatives