Jianqiao Xu

A dopamine-selective oligopeptide is verified to possess superior binding performance to model ligands over rice matrix-derived molecules in gas phase, which represents a step forward for promoting the development and...

G protein-coupled receptors (GPCRs) are targets for 36% approved drugs. However, identifying GPCR ligands remains cumbersome owing to their inherent instability and inevitably associated salts and detergents. Here, we resolve these bottlenecks by developing a stereoselective cyclic tetrapeptide (CP1) for identifying dopamine (DA) receptor ligands from complex matrices. This innovative strategy enables online coupling with liquid chromatography to reduce matrix complexity and accurate identification of putative ligands based on the high mass spectral resolution combined with the predictable pronounced mass-to-charge ratio shifts. CP1 is revealed to recognize the shared scaffolds or catecholic groups of the ligands, which is further proven tunable via conformational or submolecular modifications. Thereby, the first identification of β-phenylethylamine (β-PEA, an agonist of DA receptors) in underground water and the identification of 1-phenylguanidine (PG) and 1,3-diphenylguanidine (DPG) as antagonists of DA receptor D1 (DRD1) are achieved, raising concerns about their potential unintended effects on human dopamine receptors. This study demonstrates oligopeptides as a transformative class of gas-phase molecular tools for GPCR ligand discovery, effectively overcoming bottlenecks of conventional receptor-based methodologies.

Low water oxidation efficiency is a major barrier to efficient photocatalytic hydrogen peroxide (H ₂ O ₂ ) synthesis under sacrificial agent‐free conditions. Among various water oxidation pathways, the two‐electron water oxidation reaction (2e ⁻ WOR) is promising due to its direct H ₂ O ₂ generation and kinetic advantages. However, effective strategies to trigger the efficient 2e ⁻ WOR remain insufficient. In this study, conjugated polymers with alternating electron donor and acceptor units are designed and synthesized. By introducing an inter‐ring bonding electron donor structure with two linked phenyl rings, the efficient 2e ⁻ WOR is initiated, increasing H ₂ O ₂ synthesis efficiency from 1657 to 4401 µmol g ⁻¹ h ⁻¹ and achieving a solar‐to‐chemical conversion (SCC) efficiency of 1.25%. In‐depth studies reveal that the 2e ⁻ WOR is initiated by the inter‐ring bonding electron donor structure, which enhances electron delocalization in the highest occupied molecular orbital (HOMO), increasing the valence band potential from 1.6 to 1.8 V, thereby meeting the oxidation potential required for the 2e ⁻ WOR. Additionally, this structure promotes hole accumulation at low‐energy barrier sites, boosting water oxidation efficiency from 874 to 2767 µmol g ⁻¹ h ⁻¹ . This work presents a promising strategy for improving photocatalytic water oxidation efficiency, advancing sustainable H ₂ O ₂ production.