Utilization of maltodextrin based enantioselective, potentiometric membrane electrodes for the enantioselective assay of S-perindopril

Enantioselective, potentiometric membrane electrodes (EPMEs) based on carbon paste impregnated with different maltodextrins {dextrose equivalent (DE) 4.0-7.0 (I), 13.0-17.0 (II) and 16.5-19.5 (III)} as chiral selectors for the assay of S-perindopril is described. The proposed electrodes could be reliably employed in the assay of S-perindopril raw material and from its pharmaceutical formulation, Coversyl^® tablets. The electrode based on maltodextrin (I) showed the best enantioselectivity and time-stability. The surfaces of the electrodes are easily renewable by simply polishing on an alumina paper.     

Where organometallics and dendrimers merge: the incorporation of organometallic species into dendritic molecules

This review will describe the ongoing efforts being made to incorporate organometallic fragments into the framework of dendrimers. While purely dendritic organic molecules are well known and well studied, species incorporating organometallic moieties potentially offer many benefits that are not available to only organic containing dendrimers. For example, catalytic or redox active organometallic functions can be included in the dendritic framework and impart these characteristics onto the dendrimer. This report will give an overview of the latest developments in this field by highlighting selected examples that detail novel synthetic strategies or dendrimer construction methodologies, interesting practical applications or address specific problems associated with organometallic dendrimers.     

Conformationally Homogeneous Heterocyclic Pseudotetrapeptides as Three‐Dimensional Scaffolds for Rational Drug Design: Receptor‐Selective Somatostatin Analogues

A would‐be amide : A 1,4‐disubstituted 1,2,3‐triazole was used as a surrogate for a trans amide bond to create a library of 16 diastereomeric pseudotetrapeptides as β‐turn mimetics. High‐resolution structural analysis indicated that these scaffolds adopt distinct, rigid, conformationally homogeneous β‐turn‐like structures (see example), some of which bind somatostatin receptor subtypes selectively, and some of which show broad‐spectrum activity.

     

C?X⋅⋅⋅O Halogen Bonding: Interactions of Trifluoromethyl Halides with Dimethyl Ether

The formation of weakly bound molecular complexes between dimethyl ether (DME) and the trifluoromethyl halides CF₃Cl, CF₃Br and CF₃I dissolved in liquid argon and in liquid krypton is investigated, using Raman and FTIR spectroscopy. For all halides evidence is found for the formation of C? X???O halogen‐bonded 1:1 complexes. At higher concentrations of CF₃Br, a weak absorption due to a 1:2 complex is also observed. Using spectra recorded at temperatures between 87 and 125 K, the complexation enthalpies for the complexes are determined to be ?6.8(3) kJ mol^?1 (DME?CF₃Cl), ?10.2(1) kJ mol^?1 (DME?CF₃Br), ?15.5(1) kJ mol^?1 (DME?CF₃I), and ?17.8(5) kJ mol^?1 [DME(?CF₃Br)₂]. Structural and spectral information on the complexes is obtained from ab initio calculations at the MP2/ 6‐311++G(d,p) and MP2/6‐311++G(d,p)+LanL2DZ* levels. By applying Monte Carlo free energy perturbation calculations to account for the solvent influences, and statistical thermodynamics to estimate the zero‐point vibrational and thermal influences, the ab initio complexation energies are converted into complexation enthalpies for the solutions in liquid argon. The resulting values are compared with the experimental data deduced from the cryosolutions.     

Theoretical and experimental studies on the carbon-nanotube surface oxidation by nitric acid: interplay between functionalization and vacancy enlargement

The nitric acid oxidation of multiwalled carbon nanotubes leading to surface carboxylic groups has been investigated both experimentally and theoretically. The experimental results show that such a reaction involves the initial rapid formation of carbonyl groups, which are then transformed into phenol or carboxylic groups. At room temperature, this reaction takes place on the most reactive carbon atoms. At higher temperatures a different mechanism would operate, as evidenced by the difference in activation energies. Experimental data can be partially related to first-principles calculations, showing a multistep functionalization mechanism. The theoretical aspects of the present article have led us to propose the most efficient pathway leading to carboxylic acid functional groups on the surface. Starting from mono-vacancies, it ends up with the synergistic formation of dangling -COOH groups and the enlargement of the vacancies.     

Highly porous and robust scandium-based metal-organic frameworks for hydrogen storage

The metal-organic frameworks NOTT-400 and NOTT-401, based on a binuclear [Sc(2)(μ(2)-OH)(O(2)CR)(4)] building block, have been synthesised and characterised; the desolvated framework NOTT-401a shows a BET surface area of 1514 m(2) g(-1) with a total H(2) uptake of 4.44 wt% at 77 K and 20 bar.     

The three-dimensional model for helical columns on type-J synchronous counter-current chromatography

Unlike the existing 2-D pseudo-ring model for helical columns undergoing synchronous type-J planetary motion of counter-current chromatograph (CCC), the 3-D "helix" model developed in this work shows that there is a second normal force (i.e. the binormal force) applied virtually in the axial direction of the helical column. This force alternates in the two opposite directions and intensifies phase mixing with increasing the helix angle. On the contrary, the 2-D spiral column operated on the same CCC device lacks this third-dimensional mixing force. The (principal) normal force quantified by this "helix" model has been the same as that by the pseudo-ring model. With β>0.25, this normal centrifugal force has been one-directional and fluctuates cyclically. Different to the spiral column, this "helix" model shows that the centrifugal force (i.e. the hydrostatic force) does not contribute to stationary phase retention in the helical column. Between the popular helical columns and the emerging spiral columns for type-J synchronous CCC, this work has thus illustrated that the former is associated with better phase mixing yet poor retention for the stationary phase whereas the latter has potential for better retention for the stationary phase yet poor phase mixing. The methodology developed in this work may be regarded as a new platform for designing optimised CCC columns for analytical and engineering applications.     

Neurotoxin II bound to acetylcholine receptors in native membranes studied by dynamic nuclear polarization NMR

Methods enabling structural studies of membrane-integrated receptor systems without the necessity of purification provide an attractive perspective in membrane protein structural and molecular biology. This has become feasible in principle since the advent of dynamic nuclear polarization (DNP) magic-angle-spinning NMR spectroscopy, which delivers the required sensitivity. In this pilot study, we observed well-resolved solid-state NMR spectra of extensively (13)C-labeled neurotoxin II bound to the nicotinic acetylcholine receptor (nAChR) in native membranes. We show that TOTAPOL, a biradical required for DNP, is localized at membrane and protein surfaces. The concentration of active, membrane-attached biradical decreases with time, probably because of reactive components of the membrane preparation. An optimal distribution of active biradical has strong effects on the NMR data. The presence of inactive TOTAPOL in membrane-proximal situations but active biradical in the surrounding water/glycerol "glass" leads to well-resolved spectra, yet a considerable enhancement (ε = 12) is observed. The resulting spectra of a protein ligand bound to its receptor are paving the way for further DNP investigations of proteins embedded in native membrane patches.     

Probing the transition from hydrophilic to hydrophobic solvation with atomic scale resolution

Picosecond and femtosecond X-ray absorption spectroscopy is used to probe the changes of the solvent shell structure upon electron abstraction of aqueous iodide using an ultrashort laser pulse. The transient L(1,3) edge EXAFS at 50 ps time delay points to the formation of an expanded water cavity around the iodine atom, in good agreement with classical and quantum mechanical/molecular mechanics (QM/MM) molecular dynamics (MD) simulations. These also show that while the hydrogen atoms pointed toward iodide, they predominantly point toward the bulk solvent in the case of iodine, suggesting a hydrophobic behavior. This is further confirmed by quantum chemical (QC) calculations of I(-)/I(0)(H(2)O)(n=1-4) clusters. The L(1) edge sub-picosecond spectra point to the existence of a transient species that is not present at 50 ps. The QC calculations and the QM/MM MD simulations identify this transient species as an I(0)(OH(2)) complex inside the cavity. The simulations show that upon electron abstraction most of the water molecules move away from iodine, while one comes closer to form the complex that lives for 3-4 ps. This time is governed by the reorganization of the main solvation shell, basically the time it takes for the water molecules to reform an H-bond network. Only then is the interaction with the solvation shell strong enough to pull the water molecule of the complex toward the bulk solvent. Overall, much of the behavior at early times is determined by the reorientational dynamics of water molecules and the formation of a complete network of hydrogen bonded molecules in the first solvation shell.     

Chirped pulse Fourier transform microwave study of 2,2,2-trifluoroethyl formate

The rotational spectra of 2,2,2-trifluoroethyl formate and its three (13)C isotopologues have been measured with a molecular-beam-based, chirped-pulsed Fourier transform microwave spectrometer in combination with a conventional Balle-Flygare-type instrument up to 18 GHz. Although ab initio calculations predict the presence of two low-energy conformers (analogous to the trans and gauche forms of ethyl formate), the trans isomer was the only stable conformer observed. The r(s) geometry of the molecular main carbon frame was precisely derived based on a coplanar heavy-atom backbone of this conformer. ESPs of the two lowest energy conformers were calculated to obtain information about the role of through-space effects on their structures and relative stability.