Structure, energetics, and electronic coupling in the (TCNE2)-* encounter complex in solution: a polarizable continuum study

For the prototypical dyad (TCNE2)-*, previous in vacuo calculations indicate that sizable distortion of the equilibrium gas-phase structure may be required to reduce the donor/acceptor electronic coupling element (HDA) to the solution-phase experimental estimates. We employ the polarizable continuum model (PCM) to simulate the solvation environment for several polar solvents, finding noticeable structure change associated with the promotion of charge localization due to solvation. We have extended the counterpoise (CP) correction procedure so as to include fragment relaxation energies within the PCM model, and it would be of interest to incorporate this approach into schemes for optimizing coordinates on CP-corrected energy surfaces. The calculations include face-to-face encounter geometries as well as several lateral and twist distortions of the face-to-face structures. In proceeding from vacuum to solution, the calculated stabilization energy is reduced from -18 to -3 kcal/mol, and the calculated energy surface becomes flatter, with a somewhat larger minimum-energy separation of the monomer units (rDA). The corresponding minimum-energy structures are, respectively, delocalized and charge-localized. Using TD-DFT, spin-projected MP2 (PUMP2), and state-averaged two-configuration SCF (SA-TCSCF) calculations to evaluate HDA for symmetric encounter complex geometries (models for transition-state structures) indicates that HDA has comparable magnitude in the gas phase and in solution for a given dimer structure. SA-TCSCF calculations comparing HDA based on symmetric charge-delocalized structures and their asymmetric (minimum-energy) charge-localized counterparts (at a given rDA) yield very similar values. Even with account taken of the energetically accessible configurations probed by the PCM calculations, the HDA values remain significantly higher than the experimental estimates inferred from solution spectra and assumption of rDA based on crystal data. Clearly, additional calculations based on molecular-level solvent models would be of value in helping to characterize the intermolecular structures accessible to the encounter complex in polar solution.     

Characterization and optimization of a positively charged poly (ethylene glycol)diacrylate hydrogel as an actuating muscle tissue engineering scaffold

Hydrogels have been used for many applications in tissue engineering and regenerative medicine due to their versatile material properties and similarities to the native extracellular matrix. Poly (ethylene glycol) diacrylate (PEGDA) is an ionic electroactive polymer (EAP), a material that responds to an electric field with a change in size or shape while in an ionic solution, that may be used in the development of hydrogels. In this study, we have investigated a positively charged EAP that can bend without the need of external ions. PEGDA was modified with the positively charged molecule 2‐(methacryloyloxy)ethyl‐trimethylammonium chloride (MAETAC) to provide its own positive ions. This hydrogel was then characterized and optimized for bending and cellular biocompatibility with C2C12 mouse myoblast cells. Studies show that the polymer responds to an electric field and supports C2C12 viability.     

Nanoparticulate Pd supported catalysts: size-dependent formation of Pd(I)/Pd(0) and their role in CO elimination

A combination of time-resolved X-ray absorption spectroscopy (XAS), hard X-ray diffraction (HXRD), diffuse reflectance infrared spectroscopy (DRIFTS), and mass spectrometry (MS) reveals a series of size-dependent phenomena at Pd nanoparticles upon CO/(NO+O(2)) cycling conditions. The multitechnique approach and analysis show that such size-dependent phenomena are critical for understanding Pd CO elimination behavior and, particularly, that different Pd(I) and Pd(0) centers act as active species for a size estimated by XAS to be, respectively, below and above ca. 3 nm. The relative catalytic performance of these two noble metal species indicates the intrinsic higher activity of the Pd(I) species.     

Novel anti-Plasmodial hits identified by virtual screening of the ZINC database

Increased resistance of Plasmodium falciparum to most available drugs challenges the control of malaria. Studies with protease inhibitors have suggested important roles for the falcipain family of cysteine proteases. These enzymes act in concert with other proteases to hydrolyze host erythrocyte hemoglobin in the parasite food vacuole. In order to find potential new antimalarial drugs, we screened in silico the ZINC database using two different protocols involving structure- and ligand-based methodologies. Our search identified 19 novel low micromolar inhibitors of cultured chloroquine resistant P. falciparum. The most active compound presented an IC₅₀ value of 0.5 μM against cultured parasites and it also inhibited the cysteine protease falcipain-2 (IC₅₀ = 25.5 μM). These results identify novel classes of antimalarials that are structurally different from those currently in use and which can be further derivatized to deliver leads suitable for optimisation.     

Potential of atmospheric pressure chemical ionization source in GC‐QTOF MS for pesticide residue analysis

The potential applications of a new atmospheric pressure source for GC‐MS analysis have been investigated in this work. A list of around 100 GC‐amenable pesticides, which includes organochlorine, organophosphorus and organonitrogenated compounds, has been used to evaluate their behavior in the new source. Favoring the major formation of the molecular ion in the source has been the main goal due to the wide‐scope screening possibilities that this fact brings in comparison with the traditional, highly fragmented electron ionization spectra. Thus, the addition of water as modifier has been tested as a way to promote the generation of protonated molecules. Pesticides investigated have been classified into six groups according to their ionization/fragmentation behavior. Four of them are characterized by the abundant formation of the protonated molecule in the atmospheric pressure source, mostly being the base peak of the spectrum. These results show that wide‐scope screening could be easily performed with this source by investigating the presence of the protonated molecule ion, MH+. The developed procedure has been applied to pesticide screening in different food samples (nectarine, orange and spinach) and it has allowed the presence of several pesticides to be confirmed such as chlorpyriphos ethyl, deltamethrin and endosulfan sulfate. The availability of a quadrupole time‐of‐flight instrument made it feasible to perform additional MS/MS experiments for both standards and samples to go further in the confirmation of the identity of the detected compounds. Results shown in this paper have been obtained using a prototype source which exhibits promising features that could be applied to other analytical problems apart from those illustrated in this work. Copyright © 2010 John Wiley & Sons, Ltd.     

Euphohelioscopin A Is a PKC Activator Capable of Inducing Macrophage Differentiation

To identify small molecules that selectively control hematopoietic stem cell differentiation, we performed an unbiased screen using primary human CD34(+) cells. We identified a plant-derived natural product, euphohelioscopin A, capable of selectively differentiating CD34(+) cells down the granulocyte/monocytic lineage. Euphohelioscopin A also inhibits proliferation and induces differentiation of the myeloid leukemia cell lines THP-1 and HL-60. Mechanistic studies revealed that euphohelioscopin A is an activator of protein kinase C (PKC), and that the promonocytic effects of this natural product are mediated by PKC activation. In addition to shedding insights into normal hematopoiesis, this work may ultimately facilitate the application of stem cell therapies to a host of myeloid dysfunctions.     

Chasing changing nanoparticles with time-resolved pair distribution function methods

When materials are reduced to the nanoscale, their structure and reactivity can deviate greatly from the bulk or extended surface case. Using the archetypal example of supported Pt nanoparticles (ca. 2 nm diameter, 1 wt % Pt on Al(2)O(3)) catalyzing CO oxidation to CO(2) during cyclic redox operation, we show that high energy X-ray total scattering, used with subsecond time resolution, can yield detailed, valuable insights into the dynamic behavior of nanoscale systems. This approach reveals how these nanoparticles respond to their environment and the nature of active sites being formed and consumed within the catalytic process. Specific insight is gained into the structure of the highly active Pt surface oxide that formed on the nanoparticles during catalysis.     

Analysis of urinary nucleosides. I. Optimisation of high performance liquid chromatography/electrospray mass spectrometry

In order to optimise the analysis of urinary nucleosides by high performance liquid chromatography/mass spectrometry (HPLC/MS), the HPLC separation of these compounds was performed at different 'flow rates' and 0.2mL/min was found to give both a better separation and ionisation. The ionisation conditions were optimised to give the best intensity of the molecules quasi-molecular ions. The ion distribution profile and ionisation in both positive and negative mode were examined and the detection of the protonated molecule in positive mode chosen for further analysis. The limits of detection of the method developed are reported and representative LC/MS and LC/MS/MS spectra shown. Typical urinary nucleoside chromatograms are presented.