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.     

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.     

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.     

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...     

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.     

The effect of high intensity focused ultrasound on luciferase activity on two tumor cell lines in vitro, under the control of a CMV promoter

In this study, we compared the effect of high intensity focused ultrasound (HIFU) and thermal stress on the luciferase activity, controlled by a cytomegaly virus (CMV) promoter in an in vitro model using two tumor cell lines (M21, SCCVII). HIFU was applied in a pulsed-wave mode with increasing voltage at constant pulse duration, or thermal stress was delivered over a range of temperatures (36-52 °C) for 5 min. The resulting luciferase activity was measured in live cells using a cooled CCD camera. Luciferase activity was measured at set time intervals over a total of 48 h post-stress. Compared to baseline, the luciferase activity of the M21 tumor cell line when exposed to HIFU was approximately 54.2 ± 67.5% (p < 0.01) higher at a temperature of 42 °C, and approximately 52.9±128.5% (p < 0.01) higher at 44 °C. In the SCCVII tumor cell line, the luciferase activity after HIFU application was 55.4 ± 66.6% (p < 0.01) higher compared to baseline at a temperature of 42 °C. The M21 and SCCVII tumor cell line when exposed to thermal stress alone did not increase the luciferase activity. M21 and SCCVII tumor cells exposed to HIFU showed a maximum decrease in cell viability to 45.3 ± 7.5% and 10.3 ± 7.5%, respectively, and when exposed to thermal stress to 85.3 ± 3.5% and 20.4 ± 6.5%, respectively, compared to the untreated control. In M21 and SCCVII cells exposed to HIFU, free radicals could be detected using the dichlorofluorescein dye. Our findings demonstrate that HIFU can enhance the luciferase activity controlled by a CMV promoter. However it also has a higher damaging effect on the cells.     

Accurate heteronuclear distance measurements at all magic-angle spinning frequencies in solid-state NMR spectroscopy

Heteronuclear dipolar coupling is indispensable in revealing vital information related to the molecular structure and dynamics, as well as intermolecular interactions in various solid materials. Although numerous approaches have been developed to selectively reintroduce heteronuclear dipolar coupling under MAS, most of them lack universality and can only be applied to limited spin systems. Herein, we introduce a new and robust technique dubbed phase modulated rotary resonance (PMRR) for reintroducing heteronuclear dipolar couplings while suppressing all other interactions under a broad range of MAS conditions. The standard PMRR requires the radiofrequency (RF) field strength of only twice the MAS frequency, can efficiently recouple the dipolar couplings with a large scaling factor of 0.50, and is robust to experimental imperfections. Moreover, the adjustable window modification of PMRR, dubbed wPMRR, can improve its performance remarkably, making it well suited for the accurate determination of dipolar couplings in various spin systems. The robust performance of such pulse sequences has been verified theoretically and experimentally via model compounds, at different MAS frequencies. The application of the PMRR technique was demonstrated on the H-ZSM-5 zeolite, where the interaction between the Brønsted acidic hydroxyl groups of H-ZSM-5 and the absorbed trimethylphosphine oxide (TMPO) were probed, revealing the detailed configuration of super acid sites.

A new and robust technique dubbed phase modulated rotary resonance (PMRR) was proposed for the accurate determination of heteronuclear dipolar coupling under a broad range of MAS conditions in solid-state NMR spectroscopy.