A Facile Method for the Separation of Methionine Sulfoxide Diastereomers,Structural Assignment,and DFT Analysis

Methionine (Met) oxidation is an important biological redox node, with hundreds if not thousands of protein targets. The process yields methionine oxide (MetO). It renders the sulfur chiral, producing two distinct, diastereomerically related products. Despite the biological significance of Met oxidation, a reliable protocol to separate the resultant MetO diastereomers is currently lacking. This hampers our ability to make peptides and proteins that contain stereochemically defined MetO to then study their structural and functional properties. We have developed a facile method that uses supercritical CO₂ chromatography and allows obtaining both diastereomers in purities exceeding 99 %. ¹H NMR spectra were correlated with X-ray structural information. The stereochemical interconversion barrier at sulfur was calculated as 45.2 kcal mol⁻¹, highlighting the remarkable stereochemical stability of MetO sulfur chirality. Our protocol should open the road to synthesis and study of a wide variety of stereochemically defined MetO-containing proteins and peptides.     

Multifunctional Cationic PeptoStars as siRNA Carrier: Influence of Architecture and Histidine Modification on Knockdown Potential

RNA interference provides enormous potential for the treatment of several diseases, including cancer. Nevertheless, successful therapies based on siRNA require overcoming various challenges, such as poor pharmacokinetic characteristics of the small RNA molecule and inefficient cytosolic accumulation. In this respect, the development of functional siRNA carrier systems is a major task in biomedical research. To provide such a desired system, the synthesis of 3‐arm and 6‐arm PeptoStars is aimed for. The different branched polypept(o)idic architectures share a stealth‐like polysarcosine corona for efficient shielding and a multifunctional polylysine core, which can be independently varied in size and functionality for siRNA complexation‐, transport and intra cellular release. The special feature of star‐like polypept(o)ides is in their uniform small size (<20 nm) and a core–shell structure, which implies a high stability and stealth‐like properties and thus, they may combine long circulation times and a deep penetration of cancerous tissue. Initial toxicity and complement studies demonstrate well tolerated cationic PeptoStars with high complexation capability toward siRNA (N/P ratio up to 3:1), which can lead to potent RNAi for optimized systems. Here, the synthetic development of 3‐arm and 6‐arm polypept(o)idic star polymers, their modification with endosomolytic moieties, and first in vitro insights on RNA interference are reported on.     

Noise and correlation functions of hot carriers in semiconductors

We present a unifying theory of electronic noise appropriate to semiconductor materials in the presence of electric fields of arbitrary strength. In addition to thermal noise, a classification scheme for excess noise indicating different microscopic sources of fluctuations responsible for number and mobility fluctuations is provided. On the basis of simple two-level models, numerical calculations using a Monte Carlo technique are performed for the case of p-type Si at 77 K. The primary quantity which is evaluated by the theory is the auto-correlation function of current fluctuations which, subsequently, is analyzed in terms of correlation functions of the relevant physical variables. Accordingly, the corresponding current spectral-densities are determined and then compared with direct experimental results and/or analytical expressions. Important subjects which have been investigated are: (i) the effect of field assisted ionization on generation-recombination noise from shallow impurity levels; (ii) the contribution to the total noise spectrum of cross-correlation terms coupling fluctuations in velocity with those in energy and number; (iii) the current random telegraph signal and the corresponding spectral density associated with a mobility fluctuator. In all cases the numerical calculations are found to be in satisfactory agreement with experiments and/or analytical expressions thus fully supporting the physical reliability of the theoretical approach here proposed.List of the Symbols Used e Absolute value of the electron charge - f Frequency - f Distribution function - g ₁ Scattering strength with the scatter in state 1 - g ₂ Scattering strength with the scatter in state 2 - Reduced Planck constant - j Total current density - j _c Conduction current density - j _d Displacement current density - j _x Component along the x direction of the total current density - k Carrier wavevector - m Carrier effective mass - m ₀ Free electron mass - r Position vector - s Average sound velocity - t Time - u Fraction of ionized carriers - u _i Random telegraph signal related to carrier state - u _m Random telegraph signal related to scatterer state - v _d Ensemble average of the free carrier drift-velocity - v _i Carrier group velocity - v _t Ensemble average of the carrier velocity in the direction transverse to the applied field - v _ix Component along the x direction of the carrier group velocity - v _d ^r Ensemble average of the reduced drift-velocity - v ^r _i Reduced velocity component in the field direction of the i-th particle - v _ix ^j Reduced velocity component along the x axis of the i-th particle in band j - v ^r _ix Reduced velocity component along the x axis of the i-th particle - x _d Ensemble average of the carrier displacement along the x direction from the initial position - x _i Displacement along the x direction of the i-th carrier from the initial position - y _i i-th stochastic parameter - A Cross-sectional area of a homogeneous sample - C _I Auto-correlation function of the total current fluctuations - Auto-correlation function of the total current fluctuations due to mobility fluctuations - D Diffusion coefficient - D _t K Optical deformation potential - E Electrical field strength - E Electric field - E _x Component of the electric field along the x direction - E ₁ ⁰ Acoustic deformation potential - G Conductance - I Total current - I ₀ Total current in the voltage noise operation - I _m Total current associated with mobility fluctuations - I ^V Total current in the current noise operation - K _B Boltzmann constant - L Length of a homogeneous sample - N Number of free carriers which are instantaneously present in the device - N _A Acceptor concentration - N _I Total number of carriers inside the device participating in the transport (here assumed to be constant in time) - N _T Total number of carriers which are instantaneously present in the device - S _I Spectral density of current fluctuations - S _V Spectral density of voltage fluctuations - Spectral density of current fluctuations associated with the mobility fluctuations - Spectral density of current fluctuations due to correlations between fluctuations in number and velocity - Spectral density of current fluctuations due to generation-recombination processes - Spectral density of current fluctuations due to free carrier drift-velocity fluctuations - S _I ^l Longitudinal component with respect to the applied field of the current spectral-density - S _I ^t Transverse component with respect to the applied field of the current spectral-density - T Absolute temperature - T _e Electron temperature - V Electrical potential - V ^I Electrical potential in the voltage noise operation - W Collision rate - Z Small signal impedance - Poole-Frenkel factor - Equilibrium generation rate - _E Field dependent generation rate - Typical energy for thermally escaping from the impurity level - v _d ⁽⁰⁾ Fluctuation of the ensemble average of the driftvelocity associated with Brownian-like motion - v _d ^r(0) Fluctuation of the ensemble average of the reduced drift-velocity associated with Brownian-like motion - Carrier energy - ₀ Vacuum permittivity - _a Energy of the acceptor level - _r Relative static dielectric constant - Angle between initial and final k states - _op Optical phonon equivalent temperature - Mobility - ₀ Chemical potential - ₁ Mobility with the fluctuating scatterer in state 1 - ₂ Mobility with the fluctuating scatterer in state 2 - ₀ Crystal density - _E Field dependent volume recombination rate - _eq Equilibrium volume recombination rate - Conductivity - _g Cross-section for impact ionization - _c Average scattering time - _g Generation time - _l Carrier lifetime - _m Scatterer lifetime - _m1 Mean value of the time spent by the fluctuating scatterer in state 1 - _m2 Mean value of the time spent by the fluctuating scatterer in state 2 - _r Average recombination time - _T Transit time - Scattering rate - _AB Correlation function of the two variables A and B     

Deterministic single-photon source for distributed quantum networking

A sequence of single photons is emitted on demand from a single three-level atom strongly coupled to a high-finesse optical cavity. The photons are generated by an adiabatically driven stimulated Raman transition between two atomic ground states, with the vacuum field of the cavity stimulating one branch of the transition, and laser pulses deterministically driving the other branch. This process is unitary and therefore intrinsically reversible, which is essential for quantum communication and networking, and the photons should be appropriate for all-optical quantum information processing.     

Unexpected dimerization of 1,3‐dimethyl‐5‐methylenebarbituric acid revealed by a combined experimental and computational study

A comparison of experimental and calculated ¹³C‐nuclear magnetic resonance chemical shifts reveals the molecular structure of a dimer that was obtained by an unexpected dimerization of 1,3‐dimethyl‐5‐methylenebarbituric acid. Furthermore, the puckering angle of the cyclobutane unit linking the six‐membered rings is discussed in detail. The influence of substituents on 1,3‐position of the cyclobutane ring on the puckering angle is demonstrated based on 1,1,3,3‐tetramethylcyclobutane. Copyright © 2015 John Wiley & Sons, Ltd.     

Highly selective synthesis of catalytically active monodisperse rhodium nanocubes

Monodisperse sub-10 nm Rh nanocubes were synthesized with high selectivity (>85%) by a seedless polyol method. The {100} faces of the Rh NCs were effectively stabilized by chemically adsorbed Br- ions from trimethyl(tetradecyl)ammonium bromide (TTAB). This simple one-step polyol route can be readily applied to the preparation of Pt and Pd nanocubes. Moreover, the organic molecules of PVP and TTAB that encapsulated the Rh nanocubes did not prevent catalytic activity for pyrrole hydrogenation and CO oxidation.     

Dehydration performance of a hydrophobic DD3R zeolite membrane

The all silica DDR membrane turns out to be well suited to separate water from organic solvents under pervaporation conditions, despite its hydrophobic character. All-silica zeolites are chemically and hydrothermally more stable than aluminum containing ones and are therefore preferred for membrane applications, including for dehydration, even though these type of membranes are hydrophobic. Permeation of water, ethanol and methanol through an all-silica DDR membrane has been measured at temperatures ranging from 344 to 398 K. The hydrophobic membrane shows high water fluxes (up to 20 kg m⁻² h⁻¹). The pure water permeance is insensitive to temperature and is well described assuming weak adsorption. Excellent performance in dewatering ethanol (N=2$N=2$ kg m⁻² h⁻¹and _αw=1500${\alpha }_{\text{w}}=1500$ at 373 K and _xw=0.18$x_{\text{w}}=0.18$) is observed and the membrane is also able to selectively remove water from methanol (N=5$N=5$ kg m⁻² h⁻¹ and _αw=9${\alpha }_{\text{w}}=9$). Water could also be removed from methanol/ethanol/water (_αwater_/EtOH=1500${\alpha }_{\text{water}/\text{EtOH}}=1500$, _αMeOH_/EtOH=70${\alpha }_{\text{MeOH}/\text{EtOH}}=70$ at 373 K) mixtures, even at water feed concentrations below 1.5 mol%.     

Small molecule conformational preferences derived from crystal structure data. A medicinal chemistry focused analysis

Based on torsion angle distributions of frequently occurring substructures, conformation preferences of druglike molecules are presented, accompanied by a review of the relevant literature. First, the relevance of the Cambridge Structural Database (CSD) for drug design is demonstrated by comparing substructures present in compounds entering clinical trials with those found in the CSD and protein-bound ligands in the Protein Data Bank (PDB). Next, we briefly highlight preferred conformations of elementary acyclic systems, followed by a discussion of sulfonamide conformations. Due to their central role in medicinal chemistry, we discuss properties of aryl ring substituents in depth, including biaryl systems and systems of two aryl rings connected by two acyclic bonds. For a subset of torsion motifs, we also compare torsion angle histograms derived from CSD structures with those derived from ligands in the PDB. Furthermore, selected properties of some six- and seven-membered ring systems are discussed. The article closes with a section on attractive sulfur-oxygen contacts.