Oxygen evolution reaction: a perspective on a decade of atomic scale simulations

Multiple strategies to overcome the intrinsic limitations of the oxygen evolution reaction (OER) have been proposed by numerous research groups. Despite the substantial efforts, the driving force required for water oxidation is largely making the reaction inefficient. In the present work, we collected published studies involving DFT calculations for the OER, with the purpose to understand why the progress made so far, for lowering the overpotential of the reaction, is relatively small. The data revealed that the universal scaling relationship between HO* and HOO* intermediates is still present and robust, despite the variety in methods and structures used for calculating the binding energies of the intermediates. On the other hand, the data did not show a clear trend line regarding the O* binding. Our analysis suggested that trends in doped semiconducting oxides behave very differently from those in other oxides. This points towards a computational challenge in describing doped oxides in a realistic manner. We propose a way to overcome these computational challenges, which can be applied to simulations corresponding to doped semiconductors in general.

Multiple strategies to overcome the intrinsic limitations of the oxygen evolution reaction (OER) have been proposed by numerous research groups.     

Classical Food Quality Attributes and the Metabolic Profile of Cambuci,a Native Brazilian Atlantic Rainforest Fruit

The cambuci is a native Brazilian fruit from the Atlantic Forest biome. A soft and astringent pulp, a green color, and a sweet aroma are its main characteristics. Classical food quality attributes (fresh fruit mass, fruit height, diameters, total soluble solid, titratable acidity, and ratio) and the metabolic profile from ten accessions from three different locations were analyzed herein by analytical methods (refractometry and neutralization titration) and nuclear magnetic resonance spectroscopy. Concerning sugar content, sucrose was the predominant compound, with glucose and fructose alternating in second, depending on the accession. Citric acid was the most relevant acid, followed by shikimic and quinic acids in quite variable amounts. These three main acids vary in amounts for each accession. Ascorbic acid content emerges as an important quality attribute and makes this fruit nutritionally attractive, due to values comparable to those contained in citric fruits. The main amino acids identified in cambuci were glutamic acid individually or in comprising the tripeptide glutathione (glutamic acid, cysteine, glycine). The quality diversity of the evaluated accessions suggests the potentiality of cambuci use in future breeding programs.     

Characterization and compatibility study of desloratadine

Desloratadine (DL) is a selective antagonist of the histamine H₁ receptor, which has been widely used to treat allergic symptoms, and stands out from other drugs in this therapeutic class because it does not cause sedative effects. In the present study, the physico-chemical properties of DL were fully characterized using six analytical techniques such as Differential Scanning Calorimetry (DSC), Thermogravimetric analysis (TG/DTG), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, Powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The DSC curve shows a sharp endothermic event at 158.4 °C, and the TG/DTG curve presents two decomposition events between 178.4 and 451.9 °C. A compatibility study involving DL and nine pharmaceutical excipients generally used in pharmaceutical formulations was performed. Physical binary mixtures of DL with each excipient were prepared in a 1:1 (w/w) ratio. After preparation, the samples were analyzed immediately and the results reveal solid-state interaction with anhydrous lactose, microcrystalline cellulose, magnesium stearate, and stearic acid.     

The electrochemical reduction of CO2 on a copper electrode in 1‐n‐butyl‐3‐methyl imidazolium tetrafluoroborate (BMI.BF4) monitored by surface‐enhanced Raman scattering (SERS)

The electrochemical conversion of CO₂ into value‐added products using room temperature ionic liquids as solvent/electrolyte has been proposed as an alternative to minimize the environmental effects of CO₂ emissions. A key issue in the design of electrochemical systems for the reduction of CO₂ is the in situ identification of intermediate surface species as well as reaction products. Copper electrodes, besides being used as cathodes in the electrochemical reduction of CO₂, present surface‐enhanced Raman scattering (SERS) when properly activated. In this sense, the electrochemical reduction of CO₂ over a copper electrode in the room temperature ionic liquids 1‐n‐butyl‐3‐methyl imidazolium tetrafluoroborate (BMI.BF₄) was investigated by cyclic voltammetry and by in situ SERS. The cyclic voltammetries have shown that the presence of CO₂ on the BMI.BF₄ anticipates the reduction of BMI⁺ to the corresponding carbene. Fourier‐transform‐SERS spectra excited at 1064 nm and SERS spectra excited at 632.8 nm have shown vibrational signals from adsorbed CO. These SERS results indicated that CO adsorbs on the copper surface at two different surface sites. The observation of a 2275 cm⁻¹ vibration in the SERS spectra also confirmed the presence of chemically adsorbed CO₂. Other products of CO₂ reduction in BMI.BF₄, besides CO, were identified, including BMI carbene and the BMI‐CO₂ adduct. The SERS results also suggest that the presence of a thin film of Cu₂O on the copper surface anticipates the reduction of CO₂ to CO, an important component of syngas. Copyright © 2016 John Wiley & Sons, Ltd.     

Development and validation of an HPLC-MS/MS method to quantify clopidogrel acyl glucuronide, clopidogrel acid metabolite, and clopidogrel in plasma samples avoiding analyte back-conversion

A new sensitive and fast quantitative analytical method for the simultaneous determination of clopidogrel, its main metabolite clopidogrel carboxylic acid, and the newly described acyl glucuronide metabolite, in human plasma samples, is presented. The analytical procedures (plasma storage, handling, and extract storage in the autosampler) were optimized in order to avoid back-conversion; a known drawback in measurements of clopidogrel. Clopidogrel acyl glucuronide was confirmed as a major source of back-conversion to the parent drug in the presence of methanol, and thorough stability experiments were carried out to find the most appropriate conditions for an accurate analysis of clopidogrel and the two metabolites. The method was validated by assessing selectivity, sensitivity, linearity, accuracy, and precision for all three analytes, in accordance to Food and Drug Administration guidelines. Spiked quality controls in plasma as well as incurred samples were used to verify back-conversion in the selected conditions, with results meeting European Medicines Agency acceptance criteria (concentrations within 80–120% of the first reading). The method was then applied to a pharmacokinetic study, and for the first time, a pharmacokinetic curve of clopidogrel acyl glucuronide in human plasma is presented. The concentrations ranged up to 1,048.684 ng/mL, with a mean of 470.268 ng/mL, while clopidogrel had a mean C _max of 1.348 ng/mL; these orders of magnitude show how much the back-conversion of this metabolite may influence clopidogrel quantification if it is not properly controlled.     

Purity determination of a new antifungal drug candidate using quantitative 1H NMR spectroscopy: Method validation and comparison of calibration approaches

Quantitative nuclear magnetic resonance (qNMR) is an analytical technique that offers numerous advantages in pharmaceutical applications including minimum sample preparation and rapid data collection times with no need for response factor corrections, being a powerful tool for assaying drug content in both drug discovery and early drug development. In the present work, we have applied qNMR, using both the internal standard and the electronic reference to access in vivo concentrations 2 calibration methods, to assess the purity of RI76, a novel antifungal drug candidate. NMR acquisition and processing parameters were optimized in order to obtain spectra with intense, well-resolved signals of completely relaxed nuclei. The analytical method was validated following current guidelines, demonstrating selectivity, linearity, accuracy, precision, and robustness. The calibration approaches were statistically compared, and no significant difference was observed when comparing the obtained results and their dispersion in terms of relative standard deviation. The proposed qNMR method may, therefore, be used for both qualitative and quantitative assessments of RI76 in early drug development and for characterization of this compound.     

Quantitation of glucosamine sulfate in plasma by HPLC-MS/MS after administration of powder for oral solution formulation

A rapid method for the quantification of glucosamine in human plasma using high‐performance liquid chromatography coupled to tandem mass spectrometry was developed and validated. The sample preparation includes a simple deproteinization step, using d ‐[1‐¹³C] glucosamine hydrochloride as an internal standard. Chromatographic separation was performed on an ACE Ciano column using isocratic elution with acetonitrile and aqueous 2 mm ammonium acetate containing 0.025% formic acid (80:20). Selected reaction monitoring was performed using the transitions m/z 180.1 → m/z 72.1 and m/z 181.0 → m/z 74.6 to quantify glucosamine and internal standard, respectively. The method was validated and proved to be linear, accurate and precise over the range 50–5000 ng/mL of glucosamine. Recovery rates higher than 90% were obtained for both glucosamine and internal standard. No matrix effect was detected in the samples. The validated method was successfully applied to a pharmacokinetic study after oral administration of a powder for oral solution formulation containing glucosamine sulfate. Copyright © 2011 John Wiley & Sons, Ltd.     

Preparation and Cytotoxicity of Poly(Methyl Methacrylate) Nanoparticles for Drug Encapsulation

Summary: This work aimed to produce poly(methyl methacrylate) nanoparticles for use in drug encapsulation. The polymer nanoparticles were produced using miniemulsion polymerization technique. Monomer miniemulsion showed moderate stability and polymer average particle size was about 90 nm. PMMA nanoparticles were tested for toxicity in human leukemic cell strain K562 and they did not show any adverse effect on cell viability. Therefore, poly(methyl methacrylate) nanoparticles are suitable to encapsulate antitumor agents.     

Monitoring Methylmalonic Aciduria by NMR Urinomics

The paper reports on monitoring methylmalonic aciduria (MMA)-specific and non-specific metabolites via NMR urinomics. Five patients have been monitored over periods of time; things involved were diet, medication and occasional episodes of failing to comply with prescribed diets. An extended dataset of targeted metabolites is presented, and correlations with the type of MMA are underlined. A survey of previous NMR studies on MMA is also presented.