An active ferrocenyl triarylphosphine for palladium-catalyzed Suzuki-Miyaura cross-coupling of aryl halides

Pd-catalyzed Suzuki-Miyaura reaction of aryl chlorides was accomplished through the use of an active ferrocene-based triarylphosphine ligand. This air- and moisture-stable ligand was found to be effective for the cross-coupling of aryl halides at room temperature to 115 degrees C.     

HPLC and LC-MS studies of the transesterification reaction of methylparaben with twelve 3- to 6-carbon sugar alcohols and propylene glycol and the isomerization of the reaction products by acyl migration

Sugar alcohols and parabens are commonly used ingredients in oral suspension formulations. However, their possible incompatibility because of transesterification reaction is a concern during formulation development. In order to gain more knowledge about the reaction, a high-performance liquid chromatographic (HPLC) method is developed to separate the transesterification reaction products of methylparaben preservative with twelve 3- to 6-carbon sugar alcohols and propylene glycol. It is found that the number of peaks separated or partially separated correlate well with the number of distinct hydroxyl groups present in the sugar alcohol molecules. This means that all the hydroxyl groups in a sugar alcohol molecule can react with methylparaben to form transesterification reaction products. These products are positional isomers that have identical UV spectra with a maximum at 255 nm and the same m/z ratio for molecular ions by liquid chromatography-mass spectrometry. When isolated individually, they can isomerize (interconvert) under suitable conditions to form other positional isomers by intramolecular acyl migration. The acyl migration pathway for each of the isolated positional isomers from the transesterification reaction of methylparaben with sorbitol, ribitol, and xylitol is followed by HPLC. Based on the information, a tentative assignment of the six isomer peaks generated from the transesterification reaction between methylparaben and sorbitol is proposed.     

Easily Accessible Benzamide‐Derived P,O Ligands (Bphos) for Palladium‐Catalyzed Carbon–Nitrogen Bond‐Forming Reactions

Easily accessible benzamide‐derived hemilabile phosphine ligands were efficiently prepared through ortho‐directed lithiation of the corresponding N,N‐diethylbenzamide followed by quenching with chlorodialkylphosphines. These structurally simple hemilabile ligands were found to be highly effective in palladium‐catalyzed amination of aryl and heteroaryl chlorides. Various sterically congested and functionalized aryl halide substrates were compatible in these reaction conditions. By using optimized reaction conditions, remarkable catalyst productivity (total turnover number up to 8400) was obtained.     

Copper-catalyzed coupling of alkylamines and aryl iodides: an efficient system even in an air atmosphere

[reaction: see text] A mild method for the copper-catalyzed amination of aryl iodides is reported. This operationally simple C-N bond-forming protocol uses CuI as the catalyst and ethylene glycol as ligand in 2-propanol. A variety of functionalized aryl iodides as well as several amines were efficiently coupled using this method. This catalytic amination procedure is relatively insensitive to moisture and can be performed under an air atmosphere with comparable yield. Preliminary results on the amination of aryl bromides are also described.     

Versatile isocratic high-performance liquid chromatographic assay for propranolol and its basic, neutral and acidic metabolites in biological fluids

A comprehensive high-performance liquid chromatographic method was developed for quantitating propranolol and its known metabolites in serum, bile and urine. Analysis was performed before and after incubation of the samples with beta-glucuronidase-arylsulfatase to quantitate both free and conjugate forms of the oxidative metabolites. Fractionation of the basic, neutral and acidic metabolites was achieved by differential pH solvent extraction. The basic and neutral metabolites were extracted from the biological samples at pH 10.5 with 2% n-butanol in dichloromethane. Additional clean-up of the basic fraction by back-extraction into dilute acid was needed for those samples that were subjected to enzymatic hydrolysis. The original aqueous sample was titrated with acid to pH 1, followed by extraction of the remaining acidic metabolites into either n-butanol-dichloromethane (with unhydrolyzed serum) or carbon tetrachloride (with all other samples). Chromatographic separation of the metabolites in the different extracts was achieved on a reversed-phase C18 column, using a single isocratic mobile phase consisting of 0.044 M pH 2.7 phosphate buffer, tetrahydrofuran, methanol and acetonitrile, with the addition of n-butylamine as a competing base to control retention volume and peak shape. Detection and quantitation of propranolol and its metabolites in the low nanogram to sub-nanogram range was afforded by fluorescence at a low UV excitation wavelength. The coefficients of variation for replicate assay of spiked samples were uniformly less than 6% for all the analytes.     

Analysis of digoxin at therapeutic concentrations using high-performance liquid chromatography with post-column derivatization

A high-performance liquid chromatographic (HPLC) procedure has been developed for the analysis of digoxin in plasma at therapeutic concentrations. The assay method provides resolution of digoxin from its metabolites using a 15 cm X 4.6 mm HPLC column containing 3-micron octadecylsilane-bonded stationary phase. The effluent of the column is passed through a post-column reactor in which a fluorescent derivative is formed by the co-addition of hydrochloric acid and dehydroascorbic acid. Detection of the derivative is accomplished in a fluorometer with excitation at 336 nm and emission at 425 nm. The extraction efficiency for recovery of digoxin from plasma samples was 70% using chloroform-isopropanol (9:1) following a pre-wash with isooctane to remove endogenous substances. The calibration curve was linear (r = 0.9999) over the range 0.5-4 ng/ml digoxin in plasma using digitoxigenin as internal standard. The minimum detectable quantity of digoxin in plasma was 0.5 ng/ml at a signal-to-noise ratio of 4:1. Split-samples of digoxin control sera were assayed by the HPLC procedure and by the prescribed radioimmunoassay procedure. Excellent correlation was observed between the two methods (r = 0.999). No interference was noted when a selection of commonly co-prescribed drugs were evaluated for chromatographic co-elution or interference in detection with that of digoxin or the internal standard.     

Stability issues of the next generation solar cells

Polymer, perovskite, and dye‐sensitized solar cells (DSSCs) are promising technologies for next generation low cost photovoltaic cells. Among these, perovskite solar cells are the newest technology and have the highest efficiency, while DSSCs are closest to commercialization with several companies producing the DSSC materials and modules and existing DSSC installations. However, all three types of solar cells share a concern about lifetime and stability. For each type of devices, there are specific concerns and degradation mechanisms, and all of the devices require encapsulation and exhibit varying degrees of sensitivity to moisture, oxygen, elevated temperature and UV illumination depending on the device structure and materials used. We are discussing the stability and lifetime for each type of cells and future outlook of these technologies. (© 2016 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)     

Commuter cycling policy in Singapore: a farecard data analytics based approach

Peak-hour week-day traffic congestion is a common challenge in urban mobility. Promotion of commuter cycling can help in alleviating this problem in many cities. This paper takes a data analytics approach to propose policies for promoting commuter cycling in Singapore. It uses farecard data to assess the commuter cycling potential and develops a data-driven approach to policy making. A spatio-temporal analysis of farecard data helps in finding patterns in the potential demand for first-mile as well as end-to-end cycling. This analysis is used to suggest policies like cycling towns to promote first-mile cycling and cycling regions to enable end-to-end cycling by linking together the cycling towns. Furthermore, an optimization model is developed to make efficient choice of cycling towns and links for a given budget so as to maximize the potential number of commuter cyclists.     

A Macrocyclic Ruthenium(III) Complex Inhibits Angiogenesis with Down‐Regulation of Vascular Endothelial Growth Factor Receptor‐2 and Suppresses Tumor Growth In Vivo

A macrocyclic ruthenium(III) complex [Ru^III(N₂O₂)Cl₂]Cl ( Ru‐1 ) is reported as an inhibitor of angiogenesis and an anti‐tumor compound. The complex is relatively non‐cytotoxic towards endothelial and cancer cell lines in vitro, but specifically inhibited the processes of angiogenic endothelial cell tube formation and cancer cell invasion. Moreover, compared with known anti‐cancer ruthenium complexes, Ru‐1 is distinct in that it suppressed the expression of vascular endothelial growth factor receptor‐2 (VEGFR2), and the associated downstream signaling that is crucial to tumor angiogenesis. In addition, in vivo studies showed that Ru‐1 inhibited angiogenesis in a zebrafish model and suppressed tumor growth in nude mice bearing cancer xenografts.     

General synthesis of (salen)ruthenium(III) complexes via N...N coupling of (salen)ruthenium(VI) nitrides

Reaction of [Ru (VI)(N)(L (1))(MeOH)] (+) (L (1) = N, N'-bis(salicylidene)- o-cyclohexylenediamine dianion) with excess pyridine in CH 3CN produces [Ru (III)(L (1))(py) 2] (+) and N 2. The proposed mechanism involves initial equilibrium formation of [Ru (VI)(N)(L (1))(py)] (+), which undergoes rapid N...N coupling to produce [(py)(L (1))Ru (III) N N-Ru (III)(L (1))(py)] (2+); this is followed by pyridine substituion to give the final product. This ligand-induced N...N coupling of Ru (VI)N is utilized in the preparation of a series of new ruthenium(III) salen complexes, [Ru (III)(L)(X) 2] (+/-) (L = salen ligand; X = H 2O, 1-MeIm, py, Me 2SO, PhNH 2, ( t )BuNH 2, Cl (-) or CN (-)). The structures of [Ru (III)(L (1))(NH 2Ph) 2](PF 6) ( 6), K[Ru (III)(L (1))(CN) 2] ( 9), [Ru (III)(L (2))(NCCH 3) 2][Au (I)(CN) 2] ( 11) (L (2) = N, N'-bis(salicylidene)- o-phenylenediamine dianion) and [N ( n )Bu 4][Ru (III)(L (3))Cl 2] ( 12) (L (3) = N, N'-bis(salicylidene)ethylenediamine dianion) have been determined by X-ray crystallography.