High-resolution 13C and 43Ca solid-state NMR and computational studies of the ethylene glycol solvate of atorvastatin calcium

We report ⁴³Ca and ¹³C solid-state nuclear magnetic resonance (NMR) spectroscopic studies of the ethylene glycol solvate of atorvastatin calcium. The ¹³C and ⁴³Ca chemical shift and ⁴³Ca quadrupolar coupling tensor parameters are reported. The results are interpreted in terms of the reported X-ray diffraction crystal structure of the solvate and are compared with the NMR parameters of atorvastatin calcium trihydrate, the active pharmaceutical ingredient in Lipitor®. Hartree–Fock and density functional theory calculations of the NMR parameters based on a cluster model derived from the optimized X-ray diffraction crystal structure of the ethylene glycol solvate of atorvastatin calcium are in reasonable agreement with the experimental ⁴³Ca and ¹³C NMR measurables.     

Mitochondrial biofuel cells: expanding fuel diversity to amino acids

Although mitochondria have long been considered the powerhouse of the living cell, it is only recently that we have been able to employ these organelles for electrocatalysis in electrochemical energy conversion devices. The concept of using biological entities for energy conversion, commonly referred to as a biofuel cell, has been researched for nearly a century, but until recently the biological entities were limited to microbes or isolated enzymes. However, from the perspectives of efficient energy conversion and high volumetric catalytic activity, mitochondria may be a possible compromise between the efficiency of microbial biofuel cells and the high volumetric catalytic activity of enzymatic biofuel cells. This perspective focuses on comparing mitochondrial biofuel cells to other types of biofuel cells, as well as studying the fuel diversity that can be employed with mitochondrial biofuel cells. Pyruvate and fatty acids have previously been studied as fuels, but this perspective shows evidence that amino acids can be employed as fuels as well.     

Enhanced electrocatalytic activity of iron amino porphyrins using a flow cell for reduction of CO2 to CO

The flexibility of molecular catalysts is highly coveted for the electrochemical reduction of carbon dioxide (CO2) to carbon monoxide (CO) in both homogeneous a...     

Rheological behavior of highly loaded cellulose nanocrystal/poly(vinyl alcohol) composite suspensions

Recent emphasis on the pilot scale production of cellulosic nanomaterials has increased interest in the effective use of these materials as reinforcements for polymer composites. An important, enabling step to realizing the potential of cellulosic nanomaterials in their applications is the materials processing of CNC/polymer composites through multiple routes, i.e. melt, solution, and aqueous processing methods. Therefore, the objective of this research is to characterize the viscoelastic behavior of aqueous nanocomposite suspensions containing cellulose nanocrystals (CNCs) and a water-soluble polymer, poly(vinyl alcohol) (PVA). Specifically, small amplitude oscillatory shear measurements were performed on neat PVA solutions and CNC-loaded PVA suspensions. The experimental results indicated that the methods used in this study were able to produce high-quality nanocomposite suspensions at high CNC loadings, up to 67 wt% with respect to PVA. Additionally, the structure achieved in the nanocomposite suspensions was understood through component attributes and interactions. At CNC loadings near and less than the percolation threshold, a polymer mediated CNC network was present. At loadings well above the percolation threshold, a CNC network was present, indicated by limited molecular weight dependence of the storage modulus. Overall, these results provide increased fundamental understanding of CNC/PVA suspensions that can be leveraged to develop advanced aqueous processing methods for these materials.     

Blind prediction of cyclohexane–water distribution coefficients from the SAMPL5 challenge

In the recent SAMPL5 challenge, participants submitted predictions for cyclohexane/water distribution coefficients for a set of 53 small molecules. Distribution coefficients (log D) replace the hydration free energies that were a central part of the past five SAMPL challenges. A wide variety of computational methods were represented by the 76 submissions from 18 participating groups. Here, we analyze submissions by a variety of error metrics and provide details for a number of reference calculations we performed. As in the SAMPL4 challenge, we assessed the ability of participants to evaluate not just their statistical uncertainty, but their model uncertainty—how well they can predict the magnitude of their model or force field error for specific predictions. Unfortunately, this remains an area where prediction and analysis need improvement. In SAMPL4 the top performing submissions achieved a root-mean-squared error (RMSE) around 1.5 kcal/mol. If we anticipate accuracy in log D predictions to be similar to the hydration free energy predictions in SAMPL4, the expected error here would be around 1.54 log units. Only a few submissions had an RMSE below 2.5 log units in their predicted log D values. However, distribution coefficients introduced complexities not present in past SAMPL challenges, including tautomer enumeration, that are likely to be important in predicting biomolecular properties of interest to drug discovery, therefore some decrease in accuracy would be expected. Overall, the SAMPL5 distribution coefficient challenge provided great insight into the importance of modeling a variety of physical effects. We believe these types of measurements will be a promising source of data for future blind challenges, especially in view of the relatively straightforward nature of the experiments and the level of insight provided.     

Effects of radiation on established forensic evidence containment methods

The Federal Bureau of Investigation (FBI) Laboratory is currently exploring needs and protocols for the storage of evidentiary items contaminated with radioactive material. While a large body of knowledge on the behavior of storage polymers in radiation fields exists, this knowledge has not been applied to the field of forensics and maintaining evidentiary integrity. The focus of this research was to evaluate the behavior of several traditional evidentiary containment polymers when exposed to significant alpha, beta, gamma, neutron and mixed radiation sources. Doses were designed to simulate exposures possible during storage of materials. Several products were found to be poorly suited for use in this specific application based on standardized mechanical testing results. Remaining products were determined to warrant further investigation for the storage of radiologically-contaminated evidence.     

Polyion-sensitive membrane-based electrodes for heparin-binding foldamer analysis

Polymer membrane-based electrodes sensitive to low molecular weight heparin (LMWH) have been used to examine the binding between several preparations of LMWH and heparin-binding foldamers, which have recently been developed as potential inhibitors of the anticoagulant activity of LMWHs. It was found that the structure of the heparin-binding foldamer affects the equilibrium binding constant, K(eq), determined by analysis of the titration curves of the foldamers with LMWHs monitored with these electrodes, and further, the strength of binding depends on the specific LMWH preparation. Additionally, polymer membrane-based electrodes utilizing dinonylnaphthalene sulfonate as the ion-exchanger were developed to measure the heparin-binding foldamers directly in whole blood, and the response was found to depend on the lipophilicity and charge density of the foldamer.     

Sensitivity “Hot Spots” in the Direct Analysis in Real Time Mass Spectrometry of Nerve Agent Simulants

Presented here are findings describing the spatial-dependence of sensitivity and ion suppression effects observed with direct analysis in real time (DART). Continuous liquid infusion of dimethyl methyl phosphonate (DMMP) revealed that ion yield “hot spots” did not always correspond with the highest temperature regions within the ionization space. For instance, at lower concentrations (50 and 100 μM), the highest sensitivities were in the middle of the ionization region at 200 °C where there was a shorter ion transport distance, and the heat available to thermally desorb neutrals was moderate. Conversely, at higher DMMP concentrations (500 μM), the highest ion yield was directly in front of the DART source at 200 °C where it was exposed to the highest temperature for thermal desorption. In matching experiments, differential analyte volatility was observed to play a smaller role in relative ion suppression than differences in proton affinity and the relative sampling positions of analytes. At equimolar concentrations sampled at the same position, suppression was as high as 26× between isoquinoline (proton affinity 952 kJ mol^–1, boiling point 242 °C) and p-anisidine (proton affinity 900 kJ mol^–1, boiling point 243 °C). This effect was exacerbated when sampling positions of the two analytes differed, reaching levels of relative suppression as high as 4543.0× ± 1406.0. To mitigate this level of relative ion suppression, sampling positions and molar ratios of the analytes were modified to create conditions in which ion suppression was negligible.