No abstract

A high-throughput screen (HTS) of the MLPCN library using a homogenous fluorescence polarization assay identified a small molecule as a first-in-class direct inhibitor of Keap1-Nrf2 protein-protein interaction. The HTS hit has three chiral centers; a combination of flash and chiral chromatographic separation demonstrated that Keap1-binding activity resides predominantly in one stereoisomer (SRS)-5 designated as ML334 (LH601A), which is at least 100× more potent than the other stereoisomers. The stereochemistry of the four cis isomers was assigned using X-ray crystallography and confirmed using stereospecific synthesis. (SRS)-5 is functionally active in both an ARE gene reporter assay and an Nrf2 nuclear translocation assay. The stereospecific nature of binding between (SRS)-5 and Keap1 as well as the preliminary but tractable structure-activity relationships support its use as a lead for our ongoing optimization.

The crystal and magnetic structures of single-crystalline hexagonal LuFeO(3) films have been studied using x-ray, electron, and neutron diffraction methods. The polar structure of these films are found to persist up to 1050 K; and the switchability of the polar behavior is observed at room temperature, indicating ferroelectricity. An antiferromagnetic order was shown to occur below 440 K, followed by a spin reorientation resulting in a weak ferromagnetic order below 130 K. This observation of coexisting multiple ferroic orders demonstrates that hexagonal LuFeO(3) films are room-temperature multiferroics.

The presence of electronic phase separation in complex materials has been linked to many types of exotic behaviour, such as colossal magnetoresistance, the metal-insulator transition and high-temperature superconductivity 1-4 ; however, the mechanisms that drive the formation of coexisting electronic phases are still debated 5-8. Here we report transport measurements that show a preferential orientation of electronic phase domains driven by anisotropic long-range elastic coupling between a complex oxide film and substrate. We induce anisotropic electronic-domain formation along one axis of a pseudocubic perovskite single-crystal thin-film manganite by epitaxially locking it to an orthorhombic substrate. Simultaneous temperature-dependent resistivity measurements along the two perpendicular in-plane axes show substantial differences in the metal-insulator transition temperature and extraordinarily high anisotropic resistivities, which indicate that percolative conduction channels open more readily along one axis. These findings suggest that the origin of phase coexistence is much more strongly influenced by strain than by local chemical inhomogeneity. Complex oxides have a wide range of unique behaviours owing to their often inseparable energy overlaps of the spin-chargelattice-orbital interactions. Manganites are of particular interest owing to the speculation that their colossal-magnetoresistive behaviour is the result of emergent electronic phase separation (EPS). In the EPS model, coexisting regions with drastically different electronic properties can form into domains of the order of nanometres to micrometres in single-crystal structures. There is a great deal of debate about the mechanisms that cause EPS. At present, many theories cite local chemical disorder or complex electronic interactions as the key mechanisms 5-8 ; however, the influence of inherent crystalline strain and local lattice distortions are also thought to have a strong influence over the formation of EPS (refs 9-13). Combining these influences, theoretical models based on electronic and elastic degrees of freedom have shown that large-scale EPS can self-organize into elongated domains with no preference for uniaxial orientation 9. By applying an anisotropic long-range strain field to an EPS system, we can investigate the specific effects of elastic energy on the emergent formation of coexisting electronic phase domains. Owing to its well-known large-scale EPS into ferromagneticmetal (FMM) and charge-ordered-insulator (COI) domains, we use single-crystal thin films of La 5/8−x Pr x Ca 3/8 MnO 3 (x = 0.3) (LPCMO) as a model system and compare the transport data of two perpendicular in-plane directions in the case of an anisotropically strained orthorhombic structure. Although other methods, such as magnetic force microscopy 14-16 and out-of-plane versus in-plane transport 17 , have found evidence of local variation in domain