Screening for library-assisted identification and fully validated quantification of 22 beta-blockers in blood plasma by liquid chromatography-mass spectrometry with atmospheric pressure chemical ionization

A liquid chromatographic-mass spectrometric assay with atmospheric pressure chemical ionization (LC-APCI-MS) is presented for screening for, library-assisted identification (both in scan mode) and quantification (selected-ion mode) of the beta-blockers acebutolol, diacetolol, alprenolol, atenolol, betaxolol, bisoprolol, bupranolol, carazolol, carteolol, carvedilol, celiprolol, esmolol, labetalol, metoprolol, nadolol, nebivolol, oxprenolol, penbutolol, propranolol, sotalol, talinolol and timolol in blood plasma after mixed-mode (HCX) solid-phase extraction (SPE) and separation by reverse-phase liquid chromatography with gradient elution. The validation data were within the required limits. The assay was successfully applied to authentic plasma samples allowing confirmation of diagnosis of overdose situations as well as monitoring of patients' compliance.     

Synthèse partielle et propriétés oncostatiques des pseudo-tubulosines,analogues de l'émétine et de la tubulosine

Partial Synthesis and Oncostatic Properties of Pseudotubulosines, Analogues of Emetine and Tubulosine Pseudotubulosines, structural analogues of emetine and tubulosine, have been synthesized by either Pictet-Spengler or Bischler-Napieralski condensation from dihydrocorynantheal or corynantheidal. Spectral data, cytotoxic and oncostatic properties of these new alkaloids are described.     

Synthèse de dérivés de la benzo[c] quinolizine

The introduction of polar groups in planar polycyclic systems, for the purpose of studying their intercalating action, has been realized in the benzo[c]quinolizinium series. A functionalizing synthesis has been developed from 2-picolyl-and quinaldyllithium. Intermediate ketones or imines were cyclized by a quaternization reaction involving a concerted process. Structure and physico-chemical features of the compounds prepared were studied.     

Synthesis,Structure, and Optical Properties of Terminally Sulfur‐Functionalized Core‐Substituted Naphthalene‐Bisimide Dyes

The synthesis, characterization, and optical properties of a series of new 2,6‐disubstituted naphthalene‐bisimide dyes as molecular rods comprising terminal AcS groups is reported. The first series of dyes ( 1 – 3 ), comprising phenylhetero (Ph‐X) core substituents, cover a broad range of the VIS spectrum, ranging from yellow ( 2 ) over red ( 3 ) to blue ( 1 ). The second series of dyes contains benzylhetero (Bn‐X) core substituents ( 4 – 7 ). For the same heteroatom connecting the substituent to the naphthalene core, both series were found to display comparable colors. For the second series, the colors were blue ( 4 ), red ( 5 ), and violet ( 6, 7 ). The Ph‐X‐substituted dyes 1 – 3 are nonfluorescent, in contrast to the Bn‐X‐substituted compounds 4 – 7 . This rich variety of optical features that can be adjusted by rather small alterations of the core substituents makes these structurally very comparable molecular rods ideal candidates for optically triggered molecular‐transport investigations. Also, thanks to the terminal AcS groups, these compounds can be placed between nobel‐metal electrodes for optically triggered transport experiments.     

Hydrogen bonds of RNA are stronger than those of DNA, but NMR monitors only presence of methyl substituent in uracil/thymine

Recently, Vakonakis and LiWang (J. Am. Chem. Soc. 2004, 126, 5688) reported experimental evidence for stronger hydrogen bonds in RNA A:U than in DNA A:T base pairs, which was based on differences in NMR shielding for adenine C2. We have analyzed the proposed correlation between NMR shielding and hydrogen-bond strength using density functional theory. Although we agree with the conclusion that A:U is more strongly bound, we find no correlation between the hydrogen-bond strength and the NMR shielding of C2. Our study shows that NMR merely probes the presence/absence of the methyl group in thymine/uracil, without any relation to the strength of the hydrogen bonds involved. In other words, one cannot infer the Watson-Crick hydrogen-bond strength from the NMR shielding constant of adenine C2.     

Adrenaline recognition in water

Host molecule 1 displays a high affinity in water towards catecholamines and especially related structures such as beta-blockers with extended aromatic pi-faces (up to 7x10(3) M(-1) for each single complexation step or 5x10(7) M(-2) for both steps). The amphiphilic structural design leads to an extensive self-association of host molecules through their aromatic flanks. Above a cmc (critical micelle concentration) of 3x10(-4) M, host 1 forms micelles that produce a favorable microenvironment for hydrophobic interactions with the included guest molecules. Electrostatic attraction of the ammonium alcohol by the phosphonate anions is thus combined with hydrophobic contributions between the aromatic moieties. Ionic hydrogen bonds with polar OH or NH groups of the guest enforce the non-covalent interactions, and finally lead to increased specificity. Both its affinity and its selectivity towards adrenergic receptor substrates are greatly enhanced if the receptor molecule 1 is transferred from water into a lipid monolayer. Catecholamines and beta-blockers lead to drastically different effects at concentrations approaching the micromolar regime. Especially beta-blockers with minute structural changes can be easily distinguished from each other. In both cases, extensive hydrophobic interactions with a self-associated and/or self-organized microenvironment are largely responsible for the observed high efficiency and specificity.     

Cellular logic with orthogonal ribosomes

The creation and use of unnatural molecules to control cellular function is a long standing goal of the chemical community, but in general, these efforts have been directed at finding molecules to inhibit or activate a particular molecular target or function, or to elicit a particular phenotype. Here we show that multiple unnatural molecules (orthogonal ribosomes) can be used combinatorially, in a single cell, to program Boolean logic functions. These experiments show how attention to the molecular specificity of noncovalent interactions between unnatural macromolecules allows the synthesis of complex function from the "bottom-up" in living matter.     

A catalytic synthesis of thiosilanes and silthianes: palladium nanoparticle-mediated cross-coupling of silanes with thio phenyl and thio vinyl ethers through selective carbon-sulfur bond activation

Palladium nanoparticles generated in situ from N,N-dimethyl-acetamide (DMA) solutions of PdX(2) (X = Cl(-), OAc(-), OCOCF(3)(-)) or Pd(2)(dba)(3) by reduction with alkyl silanes R(3)SiH (R = Me, Et, i-Pr, t-Bu) are selective catalysts for the cross-coupling of the silanes R(3)SiH with phenyl and vinyl thioethers forming the corresponding thiosilanes and silthianes in high yields and under mild conditions. The method is applicable to phenyl thioglycosides, giving access to thiosilyl glycosides a new class of sugar derivatives.     

Rapid prototyping of polymer microsystems via excimer laser ablation of polymeric moulds

This study presents a novel method for rapid prototyping of polymer microsystems. The method is based on excimer laser ablation of a thermally and mechanically stable polymer, such as PEEK (poly-ether-ether-ketone). A negative of the desired microsystem is laser machined in PEEK, which can then be used directly for hot embossing or injection moulding of a series of prototypes. This approach is very rapid and considerably cheaper than more traditional approaches to toolmaking, while still performing well in terms of reproduction of tool dimensions. The reduction in time and cost for a master tool using this method opens up new possibilities for testing small series in the R&D phase of a microsystem. Finally, two particular applications of the technique are presented.