36,078 research outputs found
Cryo-EM of full-length α-synuclein reveals fibril polymorphs with a common structural kernel.
α-Synuclein (aSyn) fibrillar polymorphs have distinct in vitro and in vivo seeding activities, contributing differently to synucleinopathies. Despite numerous prior attempts, how polymorphic aSyn fibrils differ in atomic structure remains elusive. Here, we present fibril polymorphs from the full-length recombinant human aSyn and their seeding capacity and cytotoxicity in vitro. By cryo-electron microscopy helical reconstruction, we determine the structures of the two predominant species, a rod and a twister, both at 3.7 Å resolution. Our atomic models reveal that both polymorphs share a kernel structure of a bent β-arch, but differ in their inter-protofilament interfaces. Thus, different packing of the same kernel structure gives rise to distinct fibril polymorphs. Analyses of disease-related familial mutations suggest their potential contribution to the pathogenesis of synucleinopathies by altering population distribution of the fibril polymorphs. Drug design targeting amyloid fibrils in neurodegenerative diseases should consider the formation and distribution of concurrent fibril polymorphs
Apparent Scarcity of Low-Density Polymorphs of Inorganic Solids
For most inorganic solids, very few dense polymorphs and no low-density polymorphs are observed. Taking a wide range of tetrahedrally-coordinated binary solids (e.g., ZnO, GaN) as a prototypical system, we show that the apparent scarcity of low-density polymorphs is not due to significant structural or energetic limitations. Using databases of periodic networks as sources of novel crystal structures, followed by ab initio energy minimization, we predict a dense spectrum of low-density low-energy polymorphs. The diverse range of materials considered indicates that this is likely to be a general phenomenon
A Multiscale Approach for the Characterization and Crystallization of Eflucimibe Polymorphs: from Molecules to Particles
We present in this paper a generic multiscale methodology for the characterization and crystallization of eflucimibe polymorphs. The various characterization techniques used have shown that eflucimibe polymorphism is due to a conformational change of the molecule in the crystal lattice. In addition, the two polymorphs are monotropically related in the temperature range tested and have similar structures and properties (ie. interfacial tension and solubility). Consequently, it was found that for a wide range of operating conditions, the polymorphs may crystallize concomitantly. Induction time measurements and metstable zone width determination allow to infer the origin of the concomitant appearance of the polymorphs. A predominance diagram has been established which allows to perfectly control the crystallization of the desired polymorph. However, even if the stable form can be produced in a reliable way, the crystal suspension went toward a very structured gel-like network which limits the extrapolation process. Based on microscopic observation of the crystallization events performed in a microfluidic crystallizer, we propose a range of operating conditions suitable for the production of the stable form with the desired handling properties
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Ab initio prediction of the polymorph phase diagram for crystalline methanol.
Organic crystals frequently adopt multiple distinct polymorphs exhibiting different properties. The ability to predict not only what crystal forms might occur, but under what experimental thermodynamic conditions those polymorphs are stable would be immensely valuable to the pharmaceutical industry and others. Starting only from knowledge of the experimental crystal structures, this study successfully predicts the methanol crystal polymorph phase diagram from first-principles quantum chemistry, mapping out the thermodynamic regions of stability for three polymorphs over the range 0-400 K and 0-6 GPa. The agreement between the predicted and experimental phase diagrams corresponds to predicting the relative polymorph free energies to within ∼0.5 kJ mol-1 accuracy, which is achieved by employing fragment-based second-order Møller-Plesset perturbation theory and coupled cluster theory plus a quasi-harmonic treatment of the phonons
Polymorphism in metal complexes of thiazole-4-carboxylic acid
Five new molecular complexes of chemical formula [M(4-tza)₂(H₂O)₂] (M = Co, Ni, and Cu) and a complex of [Cu(4-tza)₂]∙4H₂O using thiazole-4-carboxylic acid (4-tza) as the ligand have been successfully synthesized and structurally characterized by single crystal X-ray diffraction. Two district polymorphs (α and β) are found for both [Co(4-tza)₂(H₂O)₂] and [Ni(4-tza)₂(H₂O)₂]. The effects of solvent composition and temperature on the formation of these polymorphs have been investigated and phase behaviour of the polymorphs was studied through X-ray powder diffraction. Unlike two complexes of Co and Ni, [Cu(4-tza)₂(H₂O)₂] does not display polymorphism but exhibits irreversible structural transformation from [Cu(4-tza)₂(H₂O)₂] to the dehydrated form, [Cu(4-tza)₂], upon heating
Band Electronic Structure of One- and Two-Dimensional Pentacene Molecular Crystals
We report EHT calculations of the band electronic structure of substituted pentacene derivatives and the polymorphs of the parent compound. The results show that there are wide disparities among the bandwidths and electronic dimensionalities of these compounds. The parent pentacene polymorphs are 2-dimensional in their band electronic structure with moderate dispersions; the bandwidths in the 14.1 Ã… d-spacing polymorph are noticeably larger than for the 14.5 Ã… d-spacing polymorph, reported by Campbell. Whereas the parent pentacene polymorphs adopt the well-known herringbone packing, the new, substituted pentacenes are noticeably different in their solid state structures and this is reflected in the band electronic structures. TMS adopts a highly 1-dimensional structure that leads to a large bandwidth along the stacking direction; TIPS also adopts a stacked structure, but because the molecules are laterally interleaved in the fashion of bricks in a wall, this compound is strongly 2-dimensional.
Collective dynamics in crystalline polymorphs of ZnCl: potential modelling and inelastic neutron scattering study
We report a phonon density of states measurement of -ZnCl using
the coherent inelastic neutron scattering technique and a lattice dynamical
calculation in four crystalline phases of ZnCl using a transferable
interatomic potential. The model calculations agree reasonably well with the
available experimental data on the structures, specific heat, Raman frequencies
and their pressure variation in various crystalline phases. The calculated
results have been able to provide a fair description of the vibrational as well
as the thermodynamic properties of ZnCl in all its four phases.Comment: Accepted in J. Phys.: Condens. Matte
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