A new class of highly potent NS5A inhibitors with an unsymmetric benzimidazole-difluorofluorene-imidazole core and distal [2.2.1]azabicyclic ring system was discovered. Optimization of antiviral potency and pharmacokinetics led to the identification of 39 (ledipasvir, GS-5885). Compound 39 (GT1a replicon EC50 = 31 pM) has an extended plasma half-life of 37-45 h in healthy volunteers and produces a rapid >3 log viral load reduction in monotherapy at oral doses of 3 mg or greater with once-daily dosing in genotype 1a HCV-infected patients. 39 has been shown to be safe and efficacious, with SVR12 rates up to 100% when used in combination with direct-acting antivirals having complementary mechanisms.

No abstract

Oxygen vacancies are demonstrated to be beneficial to various electrocatalytic reactions. However, integrating oxygen vacancies into an amorphous catalyst with a large specific surface area, and investigating its effect on the oxygen evolution reaction remains a great challenge. Herein, oxygen vacancies are introduced into an amorphous N, P, and F tri‐doped CoFe2O4 using ionic liquid as a dopant. Simultaneously, ultrafine MoS2 nanoclusters are anchored onto its surface to increase the specific surface area. The vacancy‐rich MoS2/NPF‐CoFe2O4 exhibits an overpotential of 250 mV and a small Tafel slope of 41 mV dec−1, which is the best spinel‐based oxygen evolution reaction (OER) electrocatalysts so far. The excellent performance is attributed to massive oxygen vacancies, amorphous structure, large surface area, and synergistic coupling effects among active species. Density‐functional theory calculations reveal that the electronic structure of the catalyst can be modulated in the presence of heteroatoms and MoS2 nanoclusters, and then the energy barriers of intermediates are decreased as well, which enhances the OER performance. This design not only provides a simple strategy to construct amorphous structures with abundant oxygen vacancies using ionic liquid‐dopants, but also presents an in‐depth insight into the OER mechanism in alkaline solution.

Defect and interface engineering are recognized as effective strategies to regulate electronic structure and improve activity of metal sulfide. However, the practical application of sulfide is restricted by their low conductivity and rapid decline in activity derived from large volume fluctuation during electrocatalysis process. More importantly, the determination of exact active site of sulfide is complicated due to the inevitable electrochemical reconstruction. Herein, ZnS nanoparticles with Zn defect are anchored onto the surface of NiCo2S4 nanosheet to construct NiCo2S4/ZnS hybrids, which exhibit outstanding oxygen evolution performance with an ultralow overpotential of 140 mV. The anchoring of defective ZnS nanoparticles inhibit the volume expansion of NiCo2S4 nanosheet during the cycling process. Density‐functional theory reveals that the build‐in interfacial potential and Zn defect can facilitate the thermodynamic formation of *O to *OOH, thus improve their intrinsic activity.

Vacancy defects of catalysts have been extensively studied and proven to be beneficial to various electrocatalytic reactions. Herein, an ultra‐stable three‐dimensional PtCu nanowire network (NNW) with ultrafine size, self‐supporting rigid structure, and Cu vacancy defects has been developed. The vacancy defect‐rich PtCu NNW exhibits an outstanding performance for the oxygen reduction reaction (ORR), with a mass activity 14.1 times higher than for the commercial Pt/C catalyst (20 %.wt, JM), which is currently the best performance. The mass activity of the PtCu NNW for methanol oxidation reaction (MOR) is 17.8 times higher than for the commercial Pt/C catalyst. Density‐functional theory (DFT) calculations indicate that the introduction of Cu vacancies enhances the adsorption capacity of Pt atoms to the HO* intermediate and simultaneously weakens the adsorption for the O* intermediate. This work presents a facile strategy to assemble efficient electrocatalysts with abundant vacancy defects, at the same time, provides an insight into the ORR mechanism in acidic solution.