Atmospheric pressure photoionization coupled to porous graphitic carbon liquid chromatography for the analysis of globotriaosylceramides. Application to Fabry disease

Globotriaosylceramides (Gb(3)) are biological compounds implicated in Fabry disease, a lysosomal storage disease due to the deficient activity of alpha-D-galactosidase A, which results in an accumulation of Gb(3) in many organs. The naturally occurring samples are composed of mixtures of several molecular species differing by the structure of the alkyl chains and the nature of the sphingoid base. Atmospheric pressure photoionization mass spectrometry (APPI-MS) proved to be an efficient method for the analysis of globotriaosylceramide molecular species, both in direct injection and by coupling with liquid chromatography (LC). In the positive ion mode, in-source fragmentations yield very precious information that can be used to determine the structure of the alkyl chains. In the negative ion mode, the chloroform solvent participates to the analyte ionization by forming an adduct with chloride ions generated in situ. Combination of LC on a Porous Graphitic Carbon stationary phase and APPI-MS allowed the detection of a great number of species from biological samples isolated from Fabry patients. This method could be an interesting analytical tool for the biochemical investigation of (sphingo) lipid metabolism.     

Asymmetric synthesis of (-)-1-hydroxyquinolizidinone, a common intermediate for the syntheses of (-)-homopumiliotoxin 223G and (-)-epiquinamide

The short and efficient asymmetric synthesis of (-)-1-hydroxyquinolizidinone was achieved in seven steps and 25.2% overall yield from readily available 5-chloropentanal. It is a key intermediate in the formal syntheses of (-)-homopumilotoxin 223G and (-)-epiquinamide.     

Synthesis,Photophysics and Nonlinear Optical Properties of Stilbenoid Pyrimidine‐Based Dyes Bearing Methylenepyran Donor Groups

The nonlinear properties and the photophysical behavior of two π‐conjugated chromophores that incorporate an electron‐deficient pyrimidine core (A) and γ‐methylenepyrans as terminal donor (D) groups have been thoroughly investigated. Both dipolar and quadrupolar branching strategies are explored and rationalized on the basis of the Frenkel exciton model. Even though a cooperative effect is clearly observed if the dimensionality is increased, the nonlinear optical (NLO) response of this series is moderate if one considers the nature of the D/A couple and the size of the chromophores (as measured by the number of π electrons). This effect was attributed to a disruption in the electronic conjugation within the dyes’ scaffold for which the geometry deviates from planarity owing to a noticeable twisting of the pyranylidene end‐groups. This latter structural parameter also has a strong influence on the excited‐state dynamics, which leads to a very efficient fluorescence quenching.     

The dynamical properties of the aromatic hydrogen bond in NH4(C6H5)4B from quasielastic neutron scattering

NH(4)(C(6)H(5))(4)B represents a prototypical system for understanding aromatic H bonds. In NH(4)(C(6)H(5))(4)B an ammonium cation is trapped in an aromatic cage of four phenyl rings and each phenyl ring serves as a hydrogen bond acceptor for the ammonium ion as donor. Here the dynamical properties of the aromatic hydrogen bond in NH(4)(C(6)H(5))(4)B were studied by quasielastic incoherent neutron scattering in a broad temperature range (20< or =T< or =350 K). We show that in the temperature range from 67 to 350 K the ammonium ions perform rotational jumps around C(3) axes. The correlation time for this motion is the lifetime of the "transient" H bonds. It varies from 1.5 ps at T=350 K to 150 ps at T=67 K. The activation energy was found to be 3.14 kJ mol, which means only 1.05 kJ mol per single H bond for reorientations around the C(3) symmetry axis of the ammonium group. This result shows that the ammonium ions have to overcome an exceptionally low barrier to rotate and thereby break their H bonds. In addition, at temperatures above 200 K local diffusive reorientational motions of the phenyl rings, probably caused by interaction with ammonium-group reorientations, were found within the experimental observation time window. At room temperature a reorientation angle of 8.4 degrees +/-2 degrees and a correlation time of 22+/-8 ps were determined for the latter. The aromatic H bonds are extremely short lived due to the low potential barriers allowing for molecular motions with a reorientational character of the donors. The alternating rupture and formation of H bonds causes very strong damping of the librational motion of the acceptors, making the transient H bond appear rather flexible.