Sheath liquid interface for the coupling of normal-phase liquid chromatography with electrospray mass spectrometry and its application to the analysis of neoflavonoids

A novel interface that allows normal-phase liquid chromatography to be coupled with electrospray ionization (ESI) is reported. A make-up solution of 60 mM ammonium acetate in methanol, infused at a 5 microl min(-1) flow-rate at the tip of the electrospray probe, provides a sheath liquid which is poorly miscible with the chromatographic effluent, but promotes efficient ionization of the targeted analytes. Protonated molecules generated in the ESI source were subjected to tandem mass spectrometric experiments in a triple-quadrupole mass spectrometer. The main fragmentation reactions were characterized for each analyte and specific mass spectral transitions were used to acquire chromatographic data in the multiple reaction monitoring detection mode. Results obtained during optimization of the sheath liquid composition and flow-rate suggest that the electrospray process was mainly under the control of the make-up solution, and that it forms an external charged layer around a neutral chromatographic mobile phase core. This sheath liquid interface was implemented for the analysis of some neoflavonoid compounds and its performance was evaluated. Limits of detection were established for calophillolide, inophyllum B, inophyllum P and inophyllum C at 100, 25, 15 and 100 ng ml(-1), respectively.     

Metalloligands for designing single-molecule and single-chain magnets

2-Hydroxy-N-{2-[2-hydroxyethyl)amino]ethyl}benzamide (L1H?) and 2-hydroxy-N-{2-[2-hydroxybutyl)amino]ethyl}benzamide (L2H?) ligands coordinate to copper ions to give anionic metalloligands, L1Cu? and L2Cu?, after deprotonation of their amide, alcohol and phenol functions. In presence of ancillary ligands as diketones, these metalloligands react with lanthanide salts to yield tetranuclear [Cu-Ln]? complexes while in presence of lanthanide salts alone, L1Cu? gives 1D chains of tetranuclear entities linked through the Ln ions. The micro-SQUID data evidence the SMM behavior of the tetranuclear Tb complexes and the SCM behavior of the Tb chain derivative.     

The production and properties of polylactide composites filled with expanded graphite

Composites have been produced by melt-blending biodegradable polylactide (PLA) with commercially available expanded graphite (EG). Using different techniques of addition, the manifold effects of EG on PLA molecular, thermo-mechanical and fire-retardant properties were evaluated. The EG nanofiller provides PLA composites with competitive functional properties. They have a high rigidity, with Young's modulus and storage modulus increasing with EG content. They also have excellent thermal stability while preserving the glass transition and melting temperature of the original PLA matrix. Purification and pre-dispersion of EG nanofiller proved beneficial for preserving PLA molecular weights and led to improved mechanical performance. The presence of dispersed graphene nanolayers in PLA significantly accelerated the polyester crystallization process. The flame retardant properties also displayed improvements with a large decrease in the maximum rate of heat release as recorded by cone calorimetry, whereas the horizontal burning test (UL94 HB) was successfully passed revealing non-dripping and char formation.     

Selectivity optimization in green chromatography by gradient stationary phase optimized selectivity liquid chromatography

Stationary phase optimized selectivity liquid chromatography (SOSLC) is a promising technique to optimize the selectivity of a given separation by using a combination of different stationary phases. Previous work has shown that SOSLC offers excellent possibilities for method development, especially after the recent modification towards linear gradient SOSLC. The present work is aimed at developing and extending the SOSLC approach towards selectivity optimization and method development for green chromatography. Contrary to current LC practices, a green mobile phase (water/ethanol/formic acid) is hereby preselected and the composition of the stationary phase is optimized under a given gradient profile to obtain baseline resolution of all target solutes in the shortest possible analysis time. With the algorithm adapted to the high viscosity property of ethanol, the principle is illustrated with a fast, full baseline resolution for a randomly selected mixture composed of sulphonamides, xanthine alkaloids and steroids.     

Efficient Synthesis of Differentiated syn‐1,2‐Diol Derivatives by Asymmetric Transfer Hydrogenation–Dynamic Kinetic Resolution of α‐Alkoxy‐Substituted β‐Ketoesters

Asymmetric transfer hydrogenation was applied to a wide range of racemic aryl α‐alkoxy‐β‐ketoesters in the presence of well‐defined, commercially available, chiral catalyst Ru^II–(N‐p‐toluenesulfonyl‐1,2‐diphenylethylenediamine) and a 5:2 mixture of formic acid and triethylamine as the hydrogen source. Under these conditions, dynamic kinetic resolution was efficiently promoted to provide the corresponding syn α‐alkoxy‐β‐hydroxyesters derived from substituted aromatic and heteroaromatic aldehydes with a high level of diastereoselectivity (diastereomeric ratio (d.r.)>99:1) and an almost perfect enantioselectivity (enantiomeric excess (ee)>99 %). Additionally, after extensive screening of the reaction conditions, the use of Ru^II‐ and Rh^III‐tethered precatalysts extended this process to more‐challenging substrates that bore alkenyl‐, alkynyl‐, and alkyl substituents to provide the corresponding syn α‐alkoxy‐β‐hydroxyesters with excellent enantiocontrol (up to 99 % ee) and good to perfect diastereocontrol (d.r.>99:1). Lastly, the synthetic utility of the present protocol was demonstrated by application to the asymmetric synthesis of chiral ester ethyl (2S)‐2‐ethoxy‐3‐(4‐hydroxyphenyl)‐propanoate, which is an important pharmacophore in a number of peroxisome proliferator‐activated receptor α/γ dual agonist advanced drug candidates used for the treatment of type‐II diabetes.     

Ruthenium‐Catalyzed Cross‐Dehydrogenative ortho‐N‐Carbazolation of Diarylamines: Versatile Access to Unsymmetrical Diamines

The dehydrogenative C–N cross‐coupling of unprotected, secondary anilines through ortho‐N‐carbazolation has been achieved using a Ru catalytic system with O₂ as the terminal oxidant. The reactions proceed in an intermolecular fashion, selectively in the ortho position. Implications for the field of organic synthesis are discussed.     

Characterization of New Specific Copper Chelators as Potential Drugs for the Treatment of Alzheimer’s Disease

The non‐controlled redox‐active metal ions, especially copper, in the brain of patients with Alzheimer disease (AD) should be considered at the origin of the intense oxidative damage in the AD brain. Several bis(8‐aminoquinoline) ligands, such as 1 and PA1637, are able to chelate Cu²⁺ with high affinity, and are specific chelators of copper with respect to iron and zinc. They are able to efficiently extract Cu²⁺ from a metal‐loaded amyloid. In addition, these tetradentate ligands are specific for the chelation of Cu²⁺ compared with Cu⁺. Consequently, the copper ion is easily released from the bis(8‐aminoquinoline) ligand under reductive conditions, and can be trapped again by a protein having some affinity for copper such as human serum albumin (HSA) proteins. In addition, the copper is not efficiently released from [Cu(CQ)₂] in reductive conditions. The catalytic production of H₂O₂ by [Cu²⁺‐Aβ_1?28]/ascorbate is inhibited in vitro by the bis(8‐aminoquinoline) 1 , suggesting that 1 should be able to play a protective role against oxidative damages induced by copper‐loaded amyloids.     

Synthesis and vibrational circular dichroism of enantiopure chiral oxorhenium(V) complexes containing the hydrotris(1-pyrazolyl)borate ligand

The infrared and vibrational circular dichroism (VCD) spectra of six chiral oxorhenium(V) complexes, bearing a hydrotris(1-pyrazolyl)borate (Tp) ligand, have been investigated. These complexes are promising candidates for observation of parity violation (symmetry breaking due to the weak nuclear force). New chiral oxorhenium complexes have been synthesized, namely, [TpReO(eta2-O(CH3)CH2CH2O-O,O)] (4a and 4b) diastereomers and [TpReO(eta2-N(CH3)CH2CH2O-N,O)] (5) and [TpReO(eta2-N(tBu)CH2CH2O-N,O)] (6) enantiomers. All compounds could be obtained in enantiomerically pure form by using either column chromatography or HPLC over chiral columns. VCD spectroscopy of these compounds and of [TpReO(eta2-N(CH3)CH(CH3)CH(Ph)O-N,O)] (2) and [TpReO(eta2-N(CH2)3CHCO2-N,O)] (3) (with chiral bidentate ligands derived, respectively, from ephedrine and proline) were studied. This allowed the absolute configuration determination of all compounds together with their conformational analysis, by comparing calculated and experimental spectra. This is the first VCD study of rhenium complexes which further demonstrates the applicability of VCD spectroscopy in determining the chirality of inorganic complexes.     

B?H,C?H,and B?C Bond Activation: The Role of Two Adjacent Agostic Interactions

Tuning the nature of the linker in a L∼BHR phosphinoborane compound led to the isolation of a ruthenium complex stabilized by two adjacent, δ‐C H and ε‐B_sp2 H, agostic interactions. Such a unique coordination mode stabilizes a 14‐electron “RuH₂P₂” fragment through connected σ‐bonds of different polarity, and affords selective B H, C H, and B C bond activation as illustrated by reactivity studies with H₂ and boranes.