Epothilone D alters normal growth, viability and microtubule dependent intracellular functions of cortical neurons in vitro.

Brain penetrant microtubule stabilising agents (MSAs) are being increasingly validated as potential therapeutic strategies for neurodegenerative diseases and traumatic injuries of the nervous system. MSAs are historically used to treat malignancies to great effect. However, this treatment strategy can also cause adverse off-target impacts, such as the generation of debilitating neuropathy and axonal loss. Understanding of the effects that individual MSAs have on neurons of the central nervous system is still incomplete. Previous research has revealed that aberrant microtubule stabilisation can perturb many neuronal functions, such as neuronal polarity, neurite outgrowth, microtubule dependant transport and overall neuronal viability. In the current study, we evaluate the dose dependant impact of epothilone D, a brain penetrant MSA, on both immature and relatively mature mouse cortical neurons in vitro. We show that epothilone D reduces the viability, growth and complexity of immature cortical neurons in a dose dependant manner. Furthermore, in relatively mature cortical neurons, we demonstrate that while cellularly lethal doses of epothilone D cause cellular demise, low sub lethal doses can also affect mitochondrial transport over time. Our results reveal an underappreciated mitochondrial disruption over a wide range of epothilone D doses and reiterate the importance of understanding the dosage, timing and intended outcome of MSAs, with particular emphasis on brain penetrant MSAs being considered to target neurons in disease and trauma.

Weyl-like points from band inversions of spin-polarised surface states in NbGeSb.

Band inversions are key to stabilising a variety of novel electronic states in solids, from topological surface states to the formation of symmetry-protected three-dimensional Dirac and Weyl points and nodal-line semimetals. Here, we create a band inversion not of bulk states, but rather between manifolds of surface states. We realise this by aliovalent substitution of Nb for Zr and Sb for S in the ZrSiS family of nonsymmorphic semimetals. Using angle-resolved photoemission and density-functional theory, we show how two pairs of surface states, known from ZrSiS, are driven to intersect each other near the Fermi level in NbGeSb, and to develop pronounced spin splittings. We demonstrate how mirror symmetry leads to protected crossing points in the resulting spin-orbital entangled surface band structure, thereby stabilising surface state analogues of three-dimensional Weyl points. More generally, our observations suggest new opportunities for engineering topologically and symmetry-protected states via band inversions of surface states.

Structure determination and crystal chemistry of large repeat mixed-layer hexaferrites.

Hexaferrites are an important class of magnetic oxides with applications in data storage and electronics. Their crystal structures are highly modular, consisting of Fe- or Ba-rich close-packed blocks that can be stacked in different sequences to form a multitude of unique structures, producing large anisotropic unit cells with lattice parameters typically >100 Šalong the stacking axis. This has limited atomic-resolution structure solutions to relatively simple examples such as Ba2Zn2Fe12O22, whilst longer stacking sequences have been modelled only in terms of block sequences, with no refinement of individual atomic coordinates or occupancies. This paper describes the growth of a series of complex hexaferrite crystals, their atomic-level structure solution by high-resolution synchrotron X-ray diffraction, electron diffraction and imaging methods, and their physical characterization by magnetometry. The structures include a new hexaferrite stacking sequence, with the longest lattice parameter of any hexaferrite with a fully determined structure.

Accelerated discovery of two crystal structure types in a complex inorganic phase field.

The discovery of new materials is hampered by the lack of efficient approaches to the exploration of both the large number of possible elemental compositions for such materials, and of the candidate structures at each composition. For example, the discovery of inorganic extended solid structures has relied on knowledge of crystal chemistry coupled with time-consuming materials synthesis with systematically varied elemental ratios. Computational methods have been developed to guide synthesis by predicting structures at specific compositions and predicting compositions for known crystal structures, with notable successes. However, the challenge of finding qualitatively new, experimentally realizable compounds, with crystal structures where the unit cell and the atom positions within it differ from known structures, remains for compositionally complex systems. Many valuable properties arise from substitution into known crystal structures, but materials discovery using this approach alone risks both missing best-in-class performance and attempting design with incomplete knowledge. Here we report the experimental discovery of two structure types by computational identification of the region of a complex inorganic phase field that contains them. This is achieved by computing probe structures that capture the chemical and structural diversity of the system and whose energies can be ranked against combinations of currently known materials. Subsequent experimental exploration of the lowest-energy regions of the computed phase diagram affords two materials with previously unreported crystal structures featuring unusual structural motifs. This approach will accelerate the systematic discovery of new materials in complex compositional spaces by efficiently guiding synthesis and enhancing the predictive power of the computational tools through expansion of the knowledge base underpinning them.

Redox-controlled potassium intercalation into two polyaromatic hydrocarbon solids.

Alkali metal intercalation into polyaromatic hydrocarbons (PAHs) has been studied intensely after reports of superconductivity in a number of potassium- and rubidium-intercalated materials. There are, however, no reported crystal structures to inform our understanding of the chemistry and physics because of the complex reactivity of PAHs with strong reducing agents at high temperature. Here we present the synthesis of crystalline K2Pentacene and K2Picene by a solid-solid insertion protocol that uses potassium hydride as a redox-controlled reducing agent to access the PAH dianions, and so enables the determination of their crystal structures. In both cases, the inserted cations expand the parent herringbone packings by reorienting the molecular anions to create multiple potassium sites within initially dense molecular layers, and thus interact with the PAH anion π systems. The synthetic and crystal chemistry of alkali metal intercalation into PAHs differs from that into fullerenes and graphite, in which the cation sites are pre-defined by the host structure.

1D self-assembly of chemisorbed thymine on Cu(110) driven by dispersion forces.

Adsorption of thymine on a defined Cu(110) surface was studied using reflection-absorption infrared spectroscopy (RAIRS), temperature programmed desorption (TPD), and scanning tunnelling microscopy (STM). In addition, density functional theory (DFT) calculations were undertaken in order to further understand the energetics of adsorption and self-assembly. The combination of RAIRS, TPD, and DFT results indicates that an upright, three-point-bonded adsorption configuration is adopted by the deprotonated thymine at room temperature. DFT calculations show that the upright configuration adopted by individual molecules arises as a direct result of strong O-Cu and N-Cu bonds between the molecule and the surface. STM data reveal that this upright thymine motif self-assembles into 1D chains, which are surprisingly oriented along the open-packed [001] direction of the metal surface and orthogonal to the alignment of the functional groups that are normally implicated in H-bonding interactions. DFT modelling of this system reveals that the molecular organisation is actually driven by dispersion interactions, which cause a slight tilt of the molecule and provide the major driving force for assembly into dimers and 1D chains. The relative orientations and distances of neighbouring molecules are amenable for π-π stacking, suggesting that this is an important contributor in the self-assembly process.