Expanding the medicinal chemistry toolbox: stereospecific generation of methyl group-containing propylene linkers

Use of alkyl substituted propylene linkers as a strategy for fine-tuning the biological activity of medicinal agents requires ready access to these substrates. Herein, a general strategy is described for stereospecifically generating 18 chiral mono- and di-methylpropylene linkers. All twelve vicinal 1,2-propylene targets were generated from methyl-3-hydroxybutanoate and all 1,3-disubstituted targets from pentane-2,4-diol.     

Dispersive mixing in a batch electrophoretic cell with Eyring fluids

The main objective of this study is analysis of dispersive mixing inside a batch electrophoretic cell due to Joule heating, especially for the case of non-Newtonian carriers. To this end, a carrier fluid that follows the Eyring rheological model is used in the analysis of the species convective-diffusive equation that describes the solute motion inside the device. The hydrodynamic problem (Bosse, M. A. et al., Electrophoresis 2002, 23, 2149-2156) of the electrophoretic cell is sequentially coupled to this equation. Then, by following a procedure based on the area-averaging method, an effective diffusion coefficient is obtained. This equation is the first a priori design equation for devices such as the ones analyzed in this contribution. It is useful in determining mixing conditions for the values of the relevant parameters of the physical system. The results of this analysis are used to study the cell behavior under several conditions imposed by their main parameters. Finally, some suggestions are offered about the use of Eyring fluids as potential carriers useful for controlling dispersive mixing in batch electrophoretic cells.     

The role of Joule heating in dispersive mixing effects in electrophoretic cells: hydrodynamic considerations

The analysis described in this contribution is focused on the effect of Joule heating generation on the hydrodynamics of batch electrophoretic cells (i.e., cells that do not display a forced convective term in the motion equation). The hydrodynamics of these cells is controlled by the viscous forces and by the buoyancy force caused by the temperature gradients due to the Joule heating generation. The analysis is based on differential models that lead to analytical and/or asymptotic solutions for the temperature and velocity profiles of the cell. The results are useful in determining the characteristics of the temperature and velocity profiles inside the cell. Furthermore, the results are excellent tools to be used in the analysis of the dispersive-mixing of solute when Joule heating generation must be accounted for. The analysis is performed by identifying two sequentially coupled problems. Thus, the "carrier fluid problem" and the "solute problem" are outlined. The former is associated with all the factors affecting the velocity profile and the latter is related to the convective-diffusion aspects that control the spreading of the solute inside the cell. The analysis of this contribution is centered on the discussion of the "carrier fluid problem" only. For the boundary conditions selected in the contribution, the study leads to the derivation of an analytical temperature and a "universal" velocity profile that feature the Joule heating number. The Grashof number is a scaling factor of the actual velocity profile. Several characteristics of these profiles are studied and some numerical illustrations have been included.     

Phase‐Field Simulation of Long‐Wavelength Line Edge Roughness in Diblock Copolymer Resists

We examine stochastic computer simulations of the Leibler‐Ohta‐Kawasaki (LOK) phase‐field model 1 , 2 and demonstrate that long‐wavelength line edge roughness (LER) and line width roughness (LWR) in a lamellar diblock copolymer resist depend monotonically on quench depth and noise strength, and that the LER and LWR spectra both exhibit a peak at k₀–the characteristic wavenumber of mesophase separation in diblock copolymers. For k ⪅ k₀, we find that the LER spectrum approximately scales like k^−1.6. These observations are consistent with previous theoretical, computational, and experimental examinations LER and LWR in diblock copolymer melts, and thus the LOK phase‐field model should be considered a capable and appropriate framework for future examination of long‐wavelength LER and LWR in block copolymer resist systems.

     

Dynamics of uniform quantum gases, I: Density and current correlations

A unified approach valid for any wavenumber q, frequency ω, and temperature T is presented for uniform ideal quantum gases allowing for a comprehensive study of number density and particle-current density response functions. Exact analytical expressions are obtained for spectral functions in terms of polylogarithms. Also, particle-number and particle-current static susceptibilities are presented which, for fugacity less than unity, additionally involve Kummer functions. The q- and T-dependent transverse-current static susceptibility is used to show explicitly that current correlations are of long range in a Bose-condensed uniform ideal gas but for bosons at T>T_c and for Fermi and Boltzmann gases at all temperatures these correlations are of short range. Contact repulsive interactions for systems of neutral quantum particles are considered within the random phase approximation. The expressions for particle-number and transverse-current susceptibilities are utilized to discuss the existence or nonexistence of superfluidity in the systems under consideration.     

Unwinding of the C‐Terminal Residues of Neuropeptide Y is critical for Y2 Receptor Binding and Activation

Despite recent breakthroughs in the structural characterization of G‐protein‐coupled receptors (GPCRs), there is only sparse data on how GPCRs recognize larger peptide ligands. NMR spectroscopy, molecular modeling, and double‐cycle mutagenesis studies were integrated to obtain a structural model of the peptide hormone neuropeptide Y (NPY) bound to its human G‐protein‐coupled Y₂ receptor (Y₂R). Solid‐state NMR measurements of specific isotope‐labeled NPY in complex with in vitro folded Y₂R reconstituted into phospholipid bicelles provided the bioactive structure of the peptide. Guided by solution NMR experiments, it could be shown that the ligand is tethered to the second extracellular loop by hydrophobic contacts. The C‐terminal α‐helix of NPY, which is formed in a membrane environment in the absence of the receptor, is unwound starting at T³² to provide optimal contacts in a deep binding pocket within the transmembrane bundle of the Y₂R.