Electrochemical C(sp3)-H Lactonization of 2-Alkylbenzoic Acids toward Phthalides.

Herein, we report direct electrochemical C(sp3)-H lactonization of 2-alkylbenzoic acids toward phthalides. The reaction provides a wide substrate scope of 2-alkylbenzoic acids bearing primary to tertiary C(sp3)-H bonds by utilizing a graphite anode, dichloromethane (DCM) solvent, hexafluoroisopropanol (HFIP) cosolvent, and n-Bu4NClO4 electrolyte. Our synthetic approach offers a simple, intuitive, and atom-economical protocol to synthesize various phthalides (25 examples, up to 92% yield) and obtain other 5- and 6-membered lactones (10 examples, up to 83% yield).

Visible-Light-Induced Organophotocatalytic Difunctionallization: Open-Air Hydroxysulfurization of Aryl Alkenes with Aryl Thiols.

Herein, we report a regioselective visible-light-induced organophotoredox catalytic difunctionalization method to prepare ß-hydroxysulfides using aryl alkenes and aryl thiols as substrates. The reaction provides a wide substrate scope of aryl alkenes (from simple styrene to complex bioactive compounds) and aryl thiols (from diverse heteroaromatic thiols to nonheteroaromatic thiols) (total 45 examples, up to 88% yield). Based on the combined experimental and computational studies, we demonstrate that in situ generated hydroperoxyl radicals from O2 in air react with benzylic radicals, which restrains the reaction between benzylic radicals and the acidic form of thiols in a classical thiol-ene radical reaction. We show that difunctionalization is possible due to the choice of bases, diluted substrate concentrations, increment in catalyst loading, and selection of suitable aryl thiols under aerobic conditions. Considering the biological importance of heteroaromatic thiols and the lack of methods to install them, our approach offers a platform to derive various ß-hydroxysulfides that contain aromatic elements.

Single-Step Approach toward Nitrones via Pyridinium Ylides: The DMAP-Catalyzed Reaction of Benzyl Halides with Nitrosoarenes.

A single-step approach is reported for the preparation of nitrones from benzyl halides and nitrosoarenes via pyridinium ylides, utilizing 4-dimethylaminopyridine (DMAP) catalyst and mild reaction conditions (Li2CO3, dimethylacetamide, and room temperature). The reaction provides both keto- and aldonitrones in high yields with a wide scope for benzyl halides and nitrosoarenes. In the same reaction system, 2-methyl-2-nitrosopropane, which does not have an aryl group, also affords the corresponding N-tert-butyl nitrones from primary benzyl bromides that have an electron-withdrawing group. As an application of the reaction, methyl 2-bromo-2-phenylacetate was used to prepare the corresponding isoxazolidine by a sequential one-pot synthesis.

4-Dimethylaminopyridine-Catalyzed Metal-Free Aerobic Oxidation of Aryl α-Halo Esters to Aryl α-Keto Esters.

A novel, metal-free aerobic oxidation method is described. 4-Dimethylaminopyridine (DMAP) successfully catalyzed the oxidation of aryl α-halo esters to corresponding aryl α-keto esters (up to 95% yield) under mild reaction conditions (Li2CO3, dimethylacetamide, air, and room temperature). A mechanism has been proposed where the oxidation proceeds through a [3 + 2] cycloaddition between O2 in an air atmosphere and pyridinium ylides. The ylides are supposedly generated from aryl α-halo esters and DMAP in the presence of carbonates. Based on the plausible mechanism, the potential of DMAP as a catalyst in oxidation reactions was extended.

Highly Selective Synthesis of Hydrazoarenes from Nitroarenes via Polystyrene-Supported Au-Nanoparticle-Catalyzed Reduction: Application to Azoarenes, Aminoarenes, and 4,4'-Diaminobiaryls.

A selective synthesis of hydrazoarene from nitroarene and its application are reported. Using polystyrene (PS) resins as solid supports for Au nanoparticles (AuNPs), polystyrene-supported Au nanoparticles (AuNPs@PS) were synthesized and characterized. In the presence of AuNPs@PS (1.0 mol %) as a catalyst, nitroarenes afforded corresponding hydrazoarenes (up to 99%) with high selectivity (up to 100%) under mild reaction conditions (NaBH4, 50% aq. EtOH, and room temperature). Depending on the reaction conditions (the amount of NaBH4, the substituent of nitroarenes, and the sequential addition of HCl), nitroarenes were converted to corresponding azoarenes (up to 95%), aminoarenes (up to 99%), and 4,4'-diaminobiaryls (up to 99%). Our easily recyclable catalytic system using a solid-phase reaction vessel provides an attractive synthetic method in an eco-friendly and sustainable manner.

Stakeholder perceptions of smart infusion pumps and drug library updates: A multisite, interdisciplinary study.

PURPOSE: Results of a questionnaire-based study to evaluate smart infusion pump end users' perceptions and understanding of the drug library update process are reported. METHODS: The Indianapolis Coalition for Patient Safety, Inc., in partnership with the Regenstrief Center for Healthcare Engineering, conducted a 33-item electronic, cross-sectional survey across 5 Indiana health systems from May through November 2017. Interdisciplinary participants identified for survey distribution included nurses, pharmacists, biomedical engineers, administrators, and medication safety officers. The survey assessed the following domains: patient safety, the drug library update process, knowledge of drug libraries and the update process, and end-user perceptions. RESULTS: A total of 778 submitted surveys were included in the data analysis, with a large majority of responses (90.2%) provided by nurses. The use of drug libraries for ensuring patient safety was deemed extremely important or important by 88% of respondents, but 36% indicated that they were unsure of whether drug libraries are updated on a routine basis in their health system. Approximately two-thirds agreed that the current update process improves quality of care (65.0%) and patient safety (68.1%). Moreover, 53.3% agreed that the current drug library update process was effective. However, less than 10% responded correctly when asked about the steps required to update the drug library. Furthermore, only 18% correctly indicated that when a pump is on it may not necessarily contain the most up-to-date version of the drug library. CONCLUSION: A survey of 5 health systems in Indianapolis identified several end-user knowledge gaps related to smart pump drug library updates. The results suggest that these gaps were most likely due to a combination of the 2-step update process and the fact that the current drug library version is not easy to find and/or user-friendly and it is unclear when an update is pending.

Synthesis of arbutin-gold nanoparticle complexes and their enhanced performance for whitening.

Arbutin, a natural polyphenol, possesses numerous biological activities including whitening, anti-oxidant, anti-cancer, anti-inflammatory activities, as well as strong reducing power, making it an ideal bioactive ingredient for preparing gold nanoparticles (GNPs). Previously, we developed a novel green, mild synthetic method for GNPs using glycosides such as arbutin as reducing agents and stabilizers. Herein, we optimized the synthetic method for glycoside-GNPs using arbutin, methyl ß-D-glucoside, and phenyl ß-D-glucoside and validated their whitening efficacy in vitro and in vivo. The resulting glycoside-GNPs were predominantly mono-dispersed and spherical (10.30-17.13 nm diameter). Compared with arbutin itself, arbutin-GNP complexes (GNP-A1 and GNP-P2) displayed enhanced whitening capabilities. Furthermore, GNP-P2 exhibited enhanced anti-inflammatory activity and lacked the toxicity associated with arbutin. Bioactive glycoside-GNP complexes may open new directions for cosmeceuticals, and GNP-P2 may serve as a useful whitening ingredient in future cosmeceutical applications.

Catalytic reduction of 4-nitrophenol with gold nanoparticles synthesized by caffeic acid.

In this study, various concentrations of caffeic acid (CA) were used to synthesize gold nanoparticles (CA-AuNPs) in order to evaluate their catalytic activity in the 4-nitrophenol reduction reaction. To facilitate catalytic activity, caffeic acid was removed by centrifugation after synthesizing CA-AuNPs. The catalytic activity of CA-AuNPs was compared with that of centrifuged CA-AuNPs (cf-CA-AuNPs). Notably, cf-CA-AuNPs exhibited up to 6.41-fold higher catalytic activity compared with CA-AuNPs. The catalytic activity was dependent on the caffeic acid concentration, and the lowest concentration (0.08 mM) produced CA-AuNPs with the highest catalytic activity. The catalytic activities of both CA-AuNPs and cf-CA-AuNPs decreased with increasing caffeic acid concentration. Furthermore, a conversion yield of 4-nitrophenol to 4-aminophenol in the reaction mixture was determined to be 99.8% using reverse-phase high-performance liquid chromatography. The product, 4-aminophenol, was purified from the reaction mixture, and its structure was confirmed by 1H-NMR. It can be concluded that the removal of the reducing agent, caffeic acid in the present study, significantly enhanced the catalytic activity of CA-AuNPs in the 4-nitrophenol reduction reaction.

Determination of hydroxy metabolites of polychlorinated biphenyls in plasma and tissue by gas chromatography/mass spectrometry.

This study examines a novel sample preparation method for the determination of 11 hydroxy metabolites of polychlorinated biphenyls (PCBs) in plasma and organ tissues, followed by gas chromatography with mass spectrometric detection (GC/MS). The clean-up method was optimized to eliminate the interference matter by using a silica column and 10 mL of n-hexane/dichloromethane (4:6, v/v) as an eluent. Solid-phase and solvent extraction procedures were used for the plasma and tissues samples, respectively. Compared to C(18) and C(8) solid-phase, C(2) showed higher extraction efficiency with n-hexane as the eluent for plasma. The hydroxy-PCB extraction recoveries achieved with this combined extraction and clean-up procedure from plasma ranged from 87 to 117%, while those from tissues ranged from 82 to 111%. The linear detector responses for propyl derivatives of hydroxy-PCBs were obtained with the coefficients of determination varying from 0.992 to 0.998 in the concentration range of 0.1-20 ng mL(-1). The method detection limits ranged from 0.1 to 0.5 ng mL(-1) in 1 mL of plasma and from 0.1 to 0.5 ng g(-1) in 1g of tissues. This procedure was successfully applied to the study of 3-OH-2,3',4,4',5-PeCB in rat plasma and liver samples after intraperitoneal injection (20 mg/kg) of 2,3',4,4',5-PeCB.