Investigation of the quantitative properties of the quadrupole orthogonal acceleration time-of-flight mass spectrometer with electrospray ionisation using 3,4-methylenedioxymethamphetamine

This paper describes the investigation of the potential of a quadrupole orthogonal acceleration time-of-flight mass spectrometer (Q-TOF) equipped with an atmospheric pressure ionisation interface for quantitative measurements of small molecules separated by reversed phase liquid chromatography. To this end, the detection limits and linear dynamic range in particular were studied in an LC/MS/MS experiment using 3,4-methylenedioxymethamphetamine standards and 3,4-methylenedioxyethylamphetamine for internal standardisation. In a second phase, the experiment was repeated with real biological extracts (whole blood, serum, and vitreous humour). A calibration for 3,4-methylenedioxymethamphetamine and its metabolite 3,4-methylenedioxyamphetamine was prepared in each of these matrices again using 3,4-methylenedioxyethylamphetamine as internal standard. The resulting quantitative data were compared with those obtained by liquid chromatography with fluorescence detection for the same extracts. The Q-TOF results revealed excellent sensitivity and a linear dynamic range of nearly four decades (2-10 000 pg on-column, r(2) = 0.9998, 1/x weighting). Furthermore, all the calibration curves prepared in biological material were superimposable, LC/MS/MS and LC-fluorescence, and the quantitative results for actual samples compared very favourably. It was concluded that the Q-TOF achieves a linear dynamic range for quantitative LC/MS/MS work exceeding that of fluorescence detection and at much better absolute sensitivity. Copyright 1999 John Wiley & Sons, Ltd.     

One-pot synthesis of oligosaccharides by combining reductive openings of benzylidene acetals and glycosylations

Combining triflic acid-promoted glycosylations of trichloroacetimidates with reductive opening of benzylidene acetals with triflic acid and triethylsilane as one-pot procedures provides access to a wide range of disaccharides and 2,4- and 3,4-branched trisaccharides.     

Working group report: Heavy-ion physics and quark-gluon plasma

This is the report of Heavy Ion Physics and Quark-Gluon Plasma at WHEPP-09 which was part of Working Group-4. Discussion and work on some aspects of quark-gluon plasma believed to have created in heavy-ion collisions and in early Universe are reported.     

Quantum space-times in the year 2002

We review certain emergent notions on the nature of space-time from noncommutative geometry and their radical implications. These ideas of space-time are suggested from developments in fuzzy physics, string theory, and deformation quantization. The review focuses on the ideas coming from fuzzy physics. We find models of quantum space-time like fuzzy S ⁴ on which states cannot be localized, but which fluctuate into other manifolds like CP³. New uncertainty principles concerning such lack of localizability on quantum space-times are formulated. Such investigations show the possibility of formulating and answering questions like the probability of finding a point of a quantum manifold in a state localized on another one. Additional striking possibilities indicated by these developments is the (generic) failure of CPT theorem and the conventional spin-statistics connection. They even suggest that Planck’s ‘constant’ may not be a constant, but an operator which does not commute with all observables. All these novel possibilities arise within the rules of conventional quantum physics, and with no serious input from gravity physics.     

Chemo-enzymatic synthesis of conformationally constrained oligosaccharides

N-Acetyllactosamine derivative 4, which has a methylene amide tether between C-6 and C-2', was enzymatically glycosylated using rat liver alpha-2,6-sialyltransferase (ST6GalI) or recombinant human fucosyltransferase V (FucT-V) to give conformationally constrained trisaccharides 5 and 6, respectively. The methylene amide linker of 4 was installed by a two-step procedure, which involved acylation of a C-6 amino function of a LacNAc derivative with chloroacetic anhydride followed by macrocyclization by nucleophilic displacement of the chloride by a C-2' hydroxyl. The conformational properties of 4 were determined by a combination of NOE and trans-glycosidic heteronuclear coupling constant measurements and molecular mechanics simulations and these studies established that the glycosidic linkage of 4 is conformationally constrained and resides in only one of the several energy minima accessible to LacNAc. The apparent kinetic parameters of transfer to LacNAc and conformationally constrained saccharides 3 and 4 indicates that fucosyltransferase V recognize LacNAc in its A-conformer whereas alpha-2,6-sialyltransferase recognizes the B-conformer of LacNAc.     

Trisaccharide mimetics of the aminoglycoside antibiotic neomycin

A highly convergent approach for the chemical synthesis of eight structurally related trisaccharides that contain 3 to 5 amino groups has been described. Fourier-transformation ion cyclotron resonance mass spectrometry (FT-ICR MS) has been employed to determine the dissociation constants (Kd) for the binding of the trisaccharides to a prototypical fragment of 16S ribosomal RNA. A compound that contained a 4,6-dideoxy-4-amino-beta-D-glucopyranoside moiety at C-3 displayed binding in the low micromolar range. It was found that small structural changes of the saccharides resulted in large differences in affinity. The described structure-activity relationship is expected to be valuable for the development of novel antibiotics that target rRNA.