Ru(II)-Catalyzed C(sp2)-H Activation Annulation: Synthesis of Fluorescent Benzoisoquinolonyl Acetate/Peptides from N-Arylamides and Ethyne at Room Temperature.

Benzoisoquinolones are aryl ring extended isoquinolinone derivatives, which are constituents of alkaloid natural products. This report describes the synthesis of novel benzoisoquinolone amino acid/peptide derivatives from the respective N-aryl amino esters/peptides through Ru-catalyzed C(sp2)-H annulation at room temperature. The N-terminal amide acts as an intrinsic directing group and coordinates with the active Ru(II) catalyst for the C-H bond activation and annulation of the aryl ring to produce benzoisoqunolone derivatives. Importantly, these benzoisoquinolinones exhibit fluorescence (QY ∼35%) in protic polar solvents, possibly due to charge transfer, and exhibit cell internalization to the cell nucleus without any significant cytotoxicity to human cell lines (HEK293T). Hence, our results are exceptional to transform standard amino acids/peptides into fluorescent peptides at room temperature in the late stage, which could be applicable for tracking specific target peptides by fluorescence microscopy.

Think before throw: waste chili stalk powder for facile scavenging of cationic dyes from water.

Chili stalk powder (CS), a non-conventional adsorbent, has been exercised for facile removal of cationic dyes from simulated and wastewater by batch technique. The prepared material has been characterized by Fourier-transform infrared spectroscopy (FTIR), Field emission scanning electron microscopy (FESEM), Brunauer-Emmett-Teller analysis (BET), powder X-ray diffraction (powder XRD), and pHZPC and tested best with methylene blue and crystal violet under ambient conditions. FTIR denotes the presence of carbonyl and polyphenolic groups, responsible for dye adsorption. BET surface area analysis evaluates the porous nature and specific surface area of the material, and powder XRD confirms its amorphous nature. The porous structure could be ascertained from the FESEM image, and energy dispersive X-ray analysis (EDX) confirms the elemental composition. The pH above pHzpc shows an increase in removal efficiency. The maximum adsorption capacities are 49.53 and 36.88 mg/g for methylene blue (MB) and crystal violet (CV) respectively. Linear as well as non-linear plots for kinetic and isotherm models were studied. Both dye uptake fits the linear plot of Langmuir adsorption isotherm (R2 = 0.999 and 0.995) and pseudo-second-order kinetics (R2 = 0.998 and 0.999). In the non-linear plot, the adsorption process for both dyes fit Langmuir (R2 = 0.999 for MB and R2 = 0.983 for CV) as well as Freundlich adsorption (R2 = 0.999 for MB and R2 = 0.994 for CV). 75.48% crystal violet (CV) and 73.35% methylene blue (MB) regeneration were successful in 1:1 methanol medium and reused for up to three cycles. The uptake mechanism is suggested to be a union of π-π stacking, electrostatic interaction, and weak hydrogen bonding. The material was tested with industrial effluent to prove its application in real wastewater treatment. Moreover, the material shows superior adsorption capacity than contemporary phytosorbents. To conclude, a zero-cost adsorbent using green chili stalk has been demonstrated for wastewater treatment.

Early Discontinuation of Apremilast in Patients with Psoriasis and Gastrointestinal Comorbidities: Rates and Associated Risk Factors.

INTRODUCTION: Apremilast, the first oral targeted treatment for moderate to severe psoriasis, is associated with diarrhea, nausea, and vomiting, which have contributed to treatment discontinuation. This study describes early apremilast discontinuation rates in patients with psoriasis, including a cohort with gastrointestinal (GI) comorbidities, and associated characteristics. METHODS: This retrospective cohort study used IBM® (now Merative™) MarketScan® commercial and Medicare claims data to identify adults with psoriasis who filled their first apremilast prescription between September 1, 2014 and March 31, 2020. Discontinuation was defined as a gap of > 30 days after exhausting the days' supply of a prescription fill. The GI comorbidity cohort included patients with ≥ 1 claim for inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), or other GI comorbidity during the study period. RESULTS: Discontinuation rates were high, regardless of previous biologic treatment or GI comorbidities. Among all patients, 25.5% discontinued within 60 days and 56.4% discontinued within 180 days. Patients who discontinued were more likely to be younger, female, and have IBD, Crohn's disease, or a mental health disorder. At 180 days, patients who used biologics previously were more likely to discontinue than biologic-naive patients. Patients with IBD discontinued at a greater rate than those without IBD at 60 days (30.3% vs 24.4%; P = 0.018) and 180 days (63.6% vs 57.2%; P = 0.026). Differences in discontinuation rates were minimal between GI comorbidity groups; patients with IBS discontinued at numerically higher rates than those without IBS. CONCLUSIONS: High rates of early discontinuation were observed for patients with and without GI comorbidities. Early discontinuation, whether attributable to poor tolerability or effectiveness, suggests the need for additional oral treatment options.

Synthesis of N-isoindolinonyl peptides via Pd-catalyzed C(sp2)-H olefination-activation and their conformational studies.

Isoindolinone is a constituent of several natural products that show a wide range of bioactivity, such as anticancer, antimicrobial, antiviral and anti-inflammatory properties. It would be interesting to explore the carbonyl group (H-bond acceptor) of isoindolinone and its structural and conformational changes. However, the synthesis of isoindolinone-comprising peptides in short steps is challenging. Herein, we have developed a synthetic methodology for introducing the isoindolinone residue to peptides via Pd-catalyzed C(sp2)-H activation/olefination, and demonstrated the conformational changes owing to the isoindolinone scaffold. Hence, isoindolinonyl peptides provide an avenue for the synthesis of novel foldamers and therapeutic agents.