The vastly increasing application of chiral Cp ligands in asymmetric catalysis results in growing demand for novel chiral Cp ligands. Herein, we report a new class of chiral Cp ligands based on 1,1'-spirobiindane, a privileged scaffold for chiral ligands and catalysts. The corresponding Rh complexes are shown to be excellent catalysts in asymmetric oxidative coupling reactions, providing axially chiral biaryls in 19-97% yields with up to 98:2 er.

Phosphodiesterase 9 (PDE9) inhibitors have been studied as potential therapeutics for treatment of diabetes and Alzheimer’s disease. Here we report a potent PDE9 inhibitor 3r that has an IC50 of 0.6 nM and >150-fold selectivity over other PDEs. The HepG2 cell-based assay shows that 3r inhibits the mRNA expression of phosphoenolpyruvate carboxykinase and glucose 6-phosphatase. These activities of 3r, together with the reasonable pharmacokinetic properties and no acute toxicity at 1200 mg/kg dosage, suggest its potential as a hypoglycemic agent. The crystal structure of PDE9-3r reveals significantly different conformation and hydrogen bonding pattern of 3r from those of previously published 28s. Both 3r and 28s form a hydrogen bond with Tyr424, a unique PDE9 residue (except for PDE8), but 3r shows an additional hydrogen bond with Ala452. This structure information might be useful for design of PDE9 inhibitors.

A series of rhodium complexes bearing sterically and electronically tunable cyclopentadienyl ligands, prepared by utilizing Co2(CO)8-mediated [2+2+1] cyclization as a key step, were synthesized. In the presence of 2.5 mol% of Cp m Rh4, unprecedented enantio­selective [4+1] annulation reaction of benzamides and alkenes was achieved with a broad substrate scope under mild reaction conditions, providing a variety of isoindolinones with excellent regio- and enantio­selectivity (up to 94% yield, 97:3 er). Preliminary mechanistic studies suggest that the reaction involves an oxidative Heck reaction and an intra­molecular enantio­selective alkene hydro­amination reaction.

The pursuit of high-performance photodetectors functioning in the solar-blind spectrum is motivated by both scientific and practical applications ranging from secure communication, monitoring, sensing, etc. In particular, the fabrication of heterojunctions based on the wide band gap semiconductors has emerged as an attractive strategy to promote the high-efficient photogenerated electron/hole pair separation. However, the precisely controlled growth of heterojunctions remains a huge challenge. The lattice mismatch leads to the formation of defects and/or dislocations at the interface, deteriorating the performance of devices and limiting their envisioned applications. Here, we demonstrate a simple one-step growth of amorphous/crystalline Ga2O3 phase junctions by using sputtering technique, yielding a large responsivity of 0.81 A/W, a superior photo-to-dark current ratio over 107, and an ultrahigh response speed of ∼12 ns. Compared to the previous reported solar-blind photodetectors, the obtained detectivity ≈ 5.67 × 1014 Jones is increased by 2 orders of magnitude. Such excellent photoresponse characteristics can be understood by the interfacial built-in field-promoted electron/hole pair separation for the amorphous/crystalline Ga2O3 phase junctions. Our results provide a novel path toward realizing high-performance optoelectronics functioning in the solar-blind spectrum.

P-n photovoltaic junctions are essential building blocks for optoelectronic devices for energy conversion. However, this photovoltaic efficiency has almost reached its theoretical limit. Here, a brand-new excitonic photovoltaic effect in 2D CsPbBr 3 /CdS heterostructures is revealed. These heterostructures, synthesized by epitaxial growth, display a clean interface and a strong interlayer coupling. The excitonic photovoltaic effect is a function of both the built-in equilibrium electrical potential energy and the chemical potential energy, which is generated by the significant concentration gradient of electrons and holes at the heterojunction interface. Excitingly, this novel photovoltaic effect results in a large open-circuit voltage of 0.76 V and a high power conversion efficiency of 17.5%. In addition, high photodetection performance, including a high photoswitch ratio (I light /I dark) of 10 5 and a fast response rate of 23 µs are obtained. These findings provide a new platform for photovoltaic applications.

Phosphodiesterase-9 (PDE9) inhibitors have been studied as potential therapeutics for treatment of central nervous system diseases and diabetes. Here, we report the discovery of a new category of PDE9 inhibitors by rational design on the basis of the crystal structures. The best compound, (S), has an IC 50 value of 11 nM against PDE9 and the racemic C33 has bioavailability of 56.5% in the rat pharmacokinetic model. The crystal structures of PDE9 in the complex with racemic C33, (R)-C33, and (S)-C33 reveal subtle conformational asymmetry of two M-loops in the PDE9 dimer and different conformations of two C33 enantiomers. The structures also identified a small hydrophobic pocket that interacts with the tyrosyl tail of (S)-C33 but not with (R)-C33, and is thus possibly useful for improvement of selectivity of PDE9 inhibitors. The asymmetry of the M-loop and the different interactions of the C33 enantiomers imply the necessity to consider the whole PDE9 dimer in the design of inhibitors.

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SUMMARY The majority of amyotrophic lateral sclerosis (ALS)-related mutations in the enzyme Cu, Zn superoxide dismutase (SOD1), as well as a post-translational modification, glutathionylation, destabilize the protein and lead to a misfolded oligomer that is toxic to motor neurons. The biophysical role of another physiological SOD1 modification, T2-phosphorylation, has remained a mystery. Here, we find that a phosphomimetic mutation, T2D, thermodynamically stabilizes SOD1 even in the context of a strongly SOD1-destabilizing mutation, A4V, one of the most prevalent and aggressive ALS-associated mutations in North America. This stabilization protects against formation of toxic SOD oligomers and positively impacts motor neuron survival in cellular assays. We solve the crystal structure of T2D-SOD1 and explain its stabilization effect using DMD simulations. These findings imply that T2-phosphorylation may be a plausible innate cellular protection response against SOD1-induced cytotoxicity, and stabilizing the SOD1 native conformation might offer us viable pharmaceutical strategies against currently incurable ALS.