Discovery and Structural Explorations of G-Protein Biased µ-Opioid Receptor Agonists.

Compounds that activate only the G-protein signalling pathway represent an effective strategy for making safer opioids. In the present study, we report the design, synthesis and evaluation of two classes of novel PZM21 derivatives containing the benzothiophene ring and biphenyl ring group respectively as biased µ-opioid receptor (µOR) agonists. The new compound SWG-LX-33 showed potent µOR agonist activity and produced µOR-dependent analgesia. SWG-LX-33 does not activate the ß-arrestin-2 signalling pathway in vitro even at high concentrations. Computational docking demonstrated the amino acid residue ASN150 to be critical for the weak efficacy and potency of µOR agonists in arrestin recruitment.

Surface-Fe enriched trimetallic (oxy)hydroxide engineered by S-incorporation and ligand anchoring toward efficient water oxidation.

Surface Fe with low-coordination plays a decisive role in the performance of OER catalysts in basic media, however, it is still a huge challenge to construct a Fe-enriched surface. Herein, a novel S-incorporation and ligand anchoring strategy is reported for in-situ synthesis of surface-Fe enriched OER catalysts. During the OER test, the co-etching of S elements and ligands enables the formation of surface-Fe enriched trimetallic (oxy)hydroxide OER catalysts. Benefiting from the high catalytic activity of Fe enriched species on surface, the electrode delivers an ultralow overpotential of 234 mV to reach the current density of 10 mA cm-2 and a superior stability over 50 h. This efficient S-incorporation and ligand anchoring strategy offers a new perspective for in-situ construction of advanced earth-abundant OER catalysts.