Structural impact of proline-directed pseudophosphorylation at AT8, AT100, and PHF1 epitopes on 441-residue tau

The intrinsically disordered protein tau becomes excessively phosphorylated and aggregates into neurofibrillary tangles in Alzheimer's disease. To obtain insight into the structural consequences of phosphorylation, we characterized a mutant protein of tau in which epitopes recognized by Alzheimer diagnostic antibodies were mimicked by mutation to glutamic acid [AT8 (S199E, S202E, T205E), AT100 (T212E and S214E), and PHF1 (S396E and S404E)]. A large number of distance restraints obtained from NMR paramagnetic relaxation enhancement in combination with ensemble conformer calculations demonstrate that pseudophosphorylation causes an opening of the transient folding of tau. Together with previous studies on the Parkinson-related protein α-synuclein, our data indicate that networks of transient long-range interactions are common properties of intrinsically disordered proteins and that their modulation is important for aggregation.     

Metal-free activation of dioxygen by graphene/g-C3N4 nanocomposites: functional dyads for selective oxidation of saturated hydrocarbons

Graphene sheet/polymeric carbon nitride nanocomposite (GSCN) functions as a metal-free catalyst to activate O(2) for the selective oxidation of secondary C-H bonds of cyclohexane. By fine-tuning the weight ratio of graphene and carbon nitride components, GSCN offers good conversion and high selectivity to corresponding ketones. Besides its high stability, this catalyst also exhibits high chemoselectivity for secondary C-H bonds of various saturated alkanes and, therefore, should be useful in overcoming challenges confronted by metal-mediated catalysis.     

Quantitative detection of C-deuterated drugs by CARS microscopy and Raman microspectroscopy

The introduction of carbon-deuterium (C-D) bonds into drug compounds by organic synthesis is a non-invasive labelling approach, which does not alter the chemical and physiological properties of the drug itself. C-deuterated drugs exhibit characteristic vibrational signatures in the C-D stretching region around 2100-2300 cm(-1), which avoids spectral interference with contributions from a complex biological environment. In this paper, the quantitative detection of C-deuterated drugs by Raman microspectroscopy and single-band CARS microscopy is examined. Concentration-dependent studies on drugs with aliphatic and aromatic C-D moieties were performed in a two-channel microfluidic chip, using the corresponding non-deuterated (C-H) isotopologues as an internal reference.     

Direct analysis of oligosaccharides and alpha hydroxy acids in fruits using electrosonic spray ionization mass spectrometry

Electrosonic spray ionization (ESSI) is a derivative technique of electrospray ionization (ESI) for mass spectrometry (MS) in which droplets are charged in the course of sonic spray. In this study, we applied ESSI MS to direct analysis of oligosaccharides and alpha hydroxy acids (AHAs) in fruits. The components were extracted from fruit fleshes by a feasible method prior to ESSI MS analysis, but the fruit juices were analyzed without further pretreatment. The results demonstrate that mainly alkali metal adducts of oligosaccharides are favorably produced in positive ion mode, while deprotonated AHAs and oligosaccharides are produced in negative ion mode. Compared with mass spectra obtained using electrospray droplet impact/secondary ion mass spectrometry (EDI/SIMS), mass spectra using ESSI make the identification of oligosaccharides more straightforward in positive ion mode than in negative ion mode.     

Highly sensitive detection of silybin based on adsorptive stripping analysis at single-sided heated screen-printed carbon electrodes modified with multi-walled carbon nanotubes with direct current heating

A new disposable multi-walled carbon nanotubes modified single-sided heated screen-printed carbon electrode (MWNT/ss-HSPCE) was fabricated. The electrochemical behavior of silybin was investigated by cyclic voltammetry and the probable electrode reaction mechanism was proposed. A simple and cheap direct current heating supplier was used to heating the electrode for adsorptive accumulation of silybin. The square wave voltammetric stripping peak current of silybin at MWNT/ss-HSPCE with an elevated electrode temperature of 50 °C only during accumulation step was dramatically improved compared with that at bare single-sided heated screen-printed carbon electrode (ss-HSPCE) without heating. This enhancement was mainly contributed to the combination of the advantages of multi-walled carbon nanotubes and electrically heated electrodes. Under optimum conditions, two detection linear ranges of silybin were from 1.0 × 10⁻⁹ to 1.0 × 10⁻⁷ M and 3.0 × 10⁻⁷ to 1.0 × 10⁻⁶ M. A detection limit of 5.0 × 10⁻¹⁰ M could be obtained (S/N = 3), which was more than two magnitudes lower than that at bare ss-HSPCE without heating. To the best of our knowledge, this was also at least two magnitudes lower than any others for electrochemical detection of silybin in the literature. Finally, the method was successfully applied to the determination of silybin in pharmaceutical tablets.     

Theoretical studies of the tunneling splitting of malonaldehyde using the multiconfiguration time-dependent Hartree approach

Full dimensional multi-configuration time-dependent Hartree calculations of the zero point energy and the tunneling splitting of malonaldehyde using a recently published potential energy surface [Y. Wang, B. J. Braams, J. M. Bowman, S. Carter, and D. P. Tew, J. Chem. Phys. 128, 224314 (2008)] are reported. The potential energy surface has been approximated by a modified version of the n-mode representation and careful convergence check has been performed to ensure accurate results. The obtained value for the splitting (23.4 cm(-1)) is in acceptable agreement with the experimental value of 21.583 cm(-1). The computed zero-point-energy is 14,670 cm(-1) which is lower than previous results of Wang et al., but likely to be about 4 cm(-1) too low because of shortcomings of the n-mode representation of the potential. The energies reported in this abstract contain a correction to account for neglected vibrational angular momentum terms.     

Complex wave patterns in an effective reaction-diffusion model for chemical reactions in microemulsions

An effective medium theory is employed to derive a simple qualitative model of a pattern forming chemical reaction in a microemulsion. This spatially heterogeneous system is composed of water nanodroplets randomly distributed in oil. While some steps of the reaction are performed only inside the droplets, the transport through the extended medium occurs by diffusion of intermediate chemical reactants as well as by collisions of the droplets. We start to model the system with heterogeneous reaction-diffusion equations and then derive an equivalent effective spatially homogeneous reaction-diffusion model by using earlier results on homogenization in heterogeneous reaction-diffusion systems [S.Alonso, M.Ba?r, and R.Kapral, J. Chem. Phys. 134, 214102 (2009)]. We study the linear stability of the spatially homogeneous state in the resulting effective model and obtain a phase diagram of pattern formation, that is qualitatively similar to earlier experimental results for the Belousov-Zhabotinsky reaction in an aerosol OT (AOT)-water-in-oil microemulsion [V.K.Vanag and I.R.Epstein, Phys. Rev. Lett. 87, 228301 (2001)]. Moreover, we reproduce many patterns that have been observed in experiments with the Belousov-Zhabotinsky reaction in an AOT oil-in-water microemulsion by direct numerical simulations.     

Microhydration effects on the electronic spectra of protonated polycyclic aromatic hydrocarbons: [naphthalene-(H2O)(n = 1,2)]H+

Vibrational and electronic spectra of protonated naphthalene (NaphH(+)) microsolvated by one and two water molecules were obtained by photofragmentation spectroscopy. The IR spectrum of the monohydrated species is consistent with a structure with the proton located on the aromatic molecule, NaphH(+)-H(2)O. Similar to isolated NaphH(+), the first electronic transition of NaphH(+)-H(2)O (S(1)) occurs in the visible range near 500 nm. The doubly hydrated species lacks any absorption in the visible range (420-600 nm) but absorbs in the UV range, similar to neutral Naph. This observation is consistent with a structure, in which the proton is located on the water moiety, Naph-(H(2)O)(2)H(+). Ab initio calculations for [Naph-(H(2)O)(n)]H(+) confirm that the excess proton transfers from Naph to the solvent cluster upon attachment of the second water molecule.