Evaluation of a multiarray system for pharmaceutical analysis by microemulsion electrokinetic chromatography

A multiplexed capillary electrophoresis (CE) system equipped with 96 channels was evaluated for high-throughput screening in drug discovery by microemulsion electrokinetic chromatography (MEEKC). Method transfer from a single channel to a multichannel CE system is described. Loss of efficiency and reduced migration times could be elucidated to the poor efficacy in Joule heat dissipation by forced air cooling in the multiarray system compared to liquid cooling in the single channel instrument. On the other hand, only 48 channels could actually be used because of the maximum total current of 3 mA. Precision data remained below 8% and 9% for migration times and peak areas, respectively. Some UV-detector cross-talk interference between neighboring capillary channels was noted. Impurities at 0.5% compared to the main peak (100%) could be detected with the multiplexed system which is 10 times lower compared to the single capillary system. Higher efficiency and improved figures of merit (absolute sensitivity and no cross-talk interferences) were obtained by using an array of only 24 capillaries.     

Incorporation of a flame retardancy enhancing phosphorus-containing diol into poly(butylene terephthalate) via solid state polycondensation: A comparative study

The phosphorus-containing aliphatic-aromatic diol 2-[4-(2-hydroxy-ethoxy)-3-(10-oxo-10-H9-oxa-10-λ5-phospha-phenanthrene-10-yl)-phenoxy]-ethanol, a potential flame retardant, was incorporated into poly(butylene terephthalate) (PBT) by solid state polycondensation. Thus, polymers with various ratios of PBT/DOPO-diol and number-average molar masses up to 57,000 g mol⁻¹ could be prepared. Their molar masses were higher than those of copolyesters with comparable composition obtained by direct melt polycondensation. Structures and properties of copolyesters produced by both methods were not significantly different after melt processing. Their thermal properties and combustion behaviour were investigated by means of DSC, TGA, and pyrolysis combustion flow calorimetry. Combustion studies revealed high char yields, very low heat release capacities and high limiting oxygen index (LOI) at rather low P-contents, indicative of better flame-retardancy properties.     

Electrochemistry/liquid chromatography/mass spectrometry as a tool in metabolism studies

Electrochemistry/liquid chromatography/mass spectrometry is a powerful complementary tool for the simulation of the oxidative metabolism of drugs and other xenobiotics.     

Structural modification of nanocrystalline ceria by ion beams

Exceptional size-dependent electronic-ionic conductivity of nanostructured ceria can significantly alter materials properties in chemical, physical, electronic and optical applications. Using energetic ions, we have demonstrated effective modification of interface volume and grain size in nanocrystalline ceria from a few nm up to ～25 nm, which is the critical region for controlling size-dependent material property. The grain size increases and follows an exponential law as a function of ion fluence that increases with temperature, while the cubic phase is stable under the irradiation. The unique self-healing response of radiation damage at grain boundaries is utilized to control the grain size at the nanoscale. Structural modification by energetic ions is proposed to achieve desirable electronic-ionic conductivity.     

Combination of spectroscopic and computational methods to get an understanding of supramolecular chemistry of drugs: from simple host systems to biomolecules

Circular dichroism (CD) spectra of non-covalent ligand : biomolecule couples contain information on the equilibrium geometries of the associated structures that can be retrieved upon comparison of the sign and intensity of the experimental CD bands with the quantum mechanically calculated rotational strengths of low energy supramolecular complexes, obtained from molecular modelling methods. For both chiral and achiral ligands this approach proved useful to reach a structure based rationale of ground and excited state properties of the non-covalent ligand : protein associates. In this Perspective we illustrate the potential of this method focusing on the main achievements of our recent spectroscopic, conformational and photochemical studies on drug-albumin complexes and collocate it in the frame of current methodologies of molecular modelling and spectroscopic investigation of ligand : biomolecule binding.     

Synthesis of 1-substituted 1,2,3,4-tetrahydrobenz[g]isoquinoline-5,10-diones

1,2-Disubstituted 1,2,3,4-tetrahydrobenz[g]isoquinoline-5,10-diones are prepared for the first time through an activated Pictet-Spengler reaction of the corresponding imines of 2-(1,4-dimethoxynaphth-2-yl)ethylamine in the presence of an acyl chloride and AlCl(3) followed by an oxidation with silver(II) oxide in nitric acid. Depending on the reaction conditions the N-trichloroacetyl protecting group could be cleaved off, converted to an N-methoxycarbonyl group or transformed to an N-(2-oxoacetamide) moiety. The synthesized 1,2-disubstituted 1,2,3,4-tetrahydrobenz[g]isoquinoline-5,10-diones constitute a new class of quinones, which has not been reported yet.     

A comparison between artificial and natural water oxidation

Two artificial water oxidation catalysts, the blue dimer and the Llobet catalyst, have been studied using hybrid DFT methods. The results are compared to those for water oxidation in the natural photosystem II enzyme. Studies on the latter system have now reached a high level of understanding, at present much higher than the one for the artificial systems. A recent high resolution X-ray structural investigation of PSII has confirmed the main features of the structure of the oxygen evolving complex (OEC) suggested by previous DFT cluster studies. The O-O bond formation mechanism suggested is of direct coupling (DC) type between an oxygen radical and a bridging oxo ligand. A similar DC mechanism is found for the Llobet catalyst, while an acid-base (AB) mechanism is preferred for the blue dimer. All of them require at least one oxygen radical. Full energy diagrams, including both redox and chemical steps, have been constructed illustrating similarities and differences to the natural system. Unlike previous DFT studies, the results of the present study suggest that the blue dimer is rate-limited by the initial redox steps, and the Llobet catalyst by O(2) release. The results could be useful for further improvement of the artificial systems.     

Wilsoniamines A and B: novel alkaloids from the temperate Australian bryozoan, Amathia wilsoni

Two novel alkaloids, wilsoniamines A and B, both possessing a hexahydropyrrolo[1,2-c]imidazol-1-one ring system that has not previously been found in nature, together with a new alkaloid, amathamide H and a known alkaloid, amathamide C were isolated from the temperate Australian bryozoan, Amathia wilsoni. MS and NMR analysis established the structure of the new compounds and indicated that the structure of amathamide C and several related compounds be revised. Amathamides C and H showed moderate anti-malarial and anti-trypanosomal activity.     

Cyclometalated Pt(IV) trans-diiodo adducts: experimental and computational studies within an homologous series of compounds

Four cyclometalated Pt(IV) compounds, 1a,b and 2a,b, were successfully obtained by oxidative addition of I(2) to 2-phenylpyridinate (PhPy) and Nile Red (NR) derived Pt(II) complexes with acetylacetonate (acac) or hexafluoroacetylacetonate (hacac) ancillary ligands. Single crystal X-ray diffraction, electrochemical, photophysical and computational studies have been performed in comparison with the analogues Pt(II) compounds, shedding new light on the role of the oxidation state of the metal centre towards both the luminescence properties and the dioxygen quenching.