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Self-adaptability is highly envisioned for artificial devices such as robots with chemical noses. For this goal, seeking catalysts with multiple and modulable reaction pathways is promising but generally hampered by inconsistent reaction conditions and negative internal interferences. Herein, we report an adaptable graphitic C6N6-based copper single-atom catalyst. It drives the basic oxidation of peroxidase substrates by a bound copper-oxo pathway, and undertakes a second gain reaction triggered by light via a free hydroxyl radical pathway. Such multiformity of reactive oxygen-related intermediates for the same oxidation reaction makes the reaction conditions capable to be the same. Moreover, the unique topological structure of CuSAC6N6 along with the specialized donor-π-acceptor linker promotes intramolecular charge separation and migration, thus inhibiting negative interferences of the above two reaction pathways. As a result, a sound basic activity and a superb gain of up to 3.6 times under household lights are observed, superior to that of the controls, including peroxidase-like catalysts, photocatalysts, or their mixtures. CuSAC6N6 is further applied to a glucose biosensor, which can intelligently switch sensitivity and linear detection range in vitro. Catalysts with multiple and modulable reaction pathways are promising but generally hampered by inconsistent reaction conditions and negative internal interferences. Herein, the authors report an adaptable graphitic C6N6-based copper singleatom catalyst [ABSTRACT FROM AUTHOR]

Daphnetin, which has been developed as a drug against obliterative vasculitis, can be rapidly and stereoselectively metabolized to an active 8-O-methylated metabolite, namely daphnetin 8-methyl ether (daphnetin-Me). Herein, a rapid, sensitive and reliable ultrafast liquid chromatography tandem mass spectrometry (UFLC-MS/MS) method was developed and validated to simultaneously determine daphnetin and daphnetin-Me in rat plasma after intragastric administration. The MS quantification for the two analytes and 3-aminocoumarin (internal standard, IS) was carried out on a triple quadrupole mass spectrometer using an ESI source in positive multiple reaction monitoring mode (daphnetin: m/z 179.15 → 51.10; daphnetin-Me: m/z 193.30 → 150.05; IS: m/z 162.00 → 106.20). The method exhibited a broad linear range of 1–2000 ng mL−1. The intra- and inter- assay precisions (RSD%) were ≤ 8.29% with the accuracies (RME%) within ± 5.95%. This newly developed method was successfully applied to a pharmacokinetic study of daphnetin after a single dose of 20 mg kg−1 in rats. Daphnetin and daphnetin-Me peaked almost at the same time. Compared with that of daphnetin, a 2.1-fold higher area under the concentration–time curve (AUC) for daphnetin-Me were observed. These results would be beneficial in facilitating further investigation of pharmacological mechanisms, as well as the rational application of daphnetin and daphnetin-containing herb preparations. [ABSTRACT FROM AUTHOR]

In this study, an imidazole-coumarin based fluorescent probe was developed for the selective and sensitive detection of Ag+ in aqueous solution. Using a combination of Job plot, NMR titrations, and DFT calculations, the binding properties between Ag+ and the probe were deeply investigated, and the results revealed a 1:1 binding stoichiometry between the probe and Ag+ with a binding constant of 1.02 × 106 M−1. The detection limit was found to be 150 nM, which satisfies the requirement for the quantitative detection of Ag+ in real water samples. Moreover, the new probe, Ic, was successfully applied to sense Ag+ in HeLa and HepG2 cells as well as in C. elegans, indicating that it could be a useful tool for the environmental monitoring of Ag+ pollution. These results demonstrated that Ic could serve as a high-efficiency and low-cost fluorescent probe for tracking Ag+ in an aquatic environment and biological organisms. [ABSTRACT FROM AUTHOR]

Andrographolide (AND) and two of its derivatives, deoxyandrographolide (DEO) and dehydroandrographolide (DEH), are widely used in clinical practice as anti-inflammatory agents. However, UDP-glucuronosyltransferase (UGT)-mediated phase II metabolism of these compounds is not fully understood. In this study, glucuronidation of AND, DEO, and DEH was characterized using liver microsomes and recombinant UGT enzymes. We isolated six glucuronides and identified them using 1D and 2D nuclear magnetic resonance (NMR) spectroscopy. We also systematically analyzed various kinetic parameters ( K, V, and CL) for glucuronidation of AND, DEO, and DEH. Among 12 commercially available UGT enzymes, UGT1A3, 1A4, 2B4, and 2B7 exhibited metabolic activities toward AND, DEO, and DEH. Further, UGT2B7 made the greatest contribution to glucuronidation of all three anti-inflammatory agents. Regioselective glucuronidation showed considerable species differences. 19- O-Glucuronides were present in liver microsomes from all species except rats. 3- O-Glucuronides were produced by pig and cynomolgus monkey liver microsomes for all compounds, and 3- O-glucuronide of DEH was detected in mouse and rat liver microsomes (RLM). Variations in K values were 48.6-fold (1.93-93.6 μM) and 49.5-fold (2.01-99.1 μM) for 19- O-glucuronide and 3- O-glucuronide formation, respectively. Total intrinsic clearances (CL) for 3- O- and 19- O-glucuronidation varied 4.8-fold (22.7-110 μL min mg), 10.6-fold (94.2-991 μL min mg), and 8.3-fold (122-1,010 μL min mg), for AND, DEH, and DEO, respectively. Our results indicate that UGT2B7 is the major UGT enzyme involved in the metabolism of AND, DEO, and DEH. Metabolic pathways in the glucuronidation of AND, DEO, and DEH showed considerable species differences. [ABSTRACT FROM AUTHOR]