The total synthesis of (+)-tedanolide

The first total synthesis of the (+)-tedanolide is described. Pivotal steps are the Felkin-selective aldol coupling between C12 and C13 and an efficient Mitsunobu macrolactonization. Selective protecting group transformations and subsequent oxidations generate the macrocyclic triketone. In the endgame of the synthesis, four TBS groups are removed in one reaction and a chemo- and stereoselective final step epoxidation generates (+)-tedanolide.     

An online nano-LC-ESI-FTICR-MS method for comprehensive characterization of endogenous fragments from amyloid β and amyloid precursor protein in human and cat cerebrospinal fluid

Amyloid precursor protein (APP) is the precursor protein to amyloid β (Aβ), the main constituent of senile plaques in Alzheimer's disease (AD). Endogenous Aβ peptides reflect the APP processing, and greater knowledge of different APP degradation pathways is important to understand the mechanism underlying AD pathology. When one analyzes longer Aβ peptides by low-energy collision-induced dissociation tandem mass spectrometry (MS/MS), mainly long b-fragments are observed, limiting the possibility to determine variations such as amino acid variants or post-translational modifications (PTMs) within the N-terminal half of the peptide. However, by using electron capture dissociation (ECD), we obtained a more comprehensive sequence coverage for several APP/Aβ peptide species, thus enabling a deeper characterization of possible variants and PTMs. Abnormal APP/Aβ processing has also been described in the lysosomal storage disease Niemann-Pick type C and the major large animal used for studying this disease is cat. By ECD MS/MS, a substitution of Asp7 → Glu in cat Aβ was identified. Further, sialylated core 1 like O-glycans at Tyr10, recently discovered in human Aβ (a previously unknown glycosylation type), were identified also in cat cerebrospinal fluid (CSF). It is therefore likely that this unusual type of glycosylation is common for (at least) species belonging to the magnorder Boreoeutheria. We here describe a detailed characterization of endogenous APP/Aβ peptide species in CSF by using an online top-down MS-based method.     

Nd[Al(iPrO)4]3, a novel tetranuclear alkoxide forming merohedrally twinned crystals

The new tetranuclear alkoxide hexa‐μ₂‐isopropoxy‐1:2κ⁴O;1:3κ⁴O;1:4κ⁴O‐hexaisopropoxy‐2κ²O,3κ²O,4κ²O‐trialumin­ium(III)­neodymium(III), [Nd{Al(C₃H₇O)₄}₃], has a metal–oxy­gen NdAl₃O₁₂ core which consists of four metal atoms arranged in an approximately planar triangular geometry. The central Nd atom is six‐coordinated by O atoms and the Al atoms are four‐coordinated by O atoms.     

A New Way of Using Semidefinite Programming with Applications to Linear Equations mod p

We introduce a new method of constructing approximation algorithms for combinatorial optimization problems using semidefinite programming. It consists of expressing each combinatorial object in the original problem as a constellation of vectors in the semidefinite program. When we apply this technique to systems of linear equations mod p with at most two variables in each equation, we can show that the problem is approximable within (1 − κ(p))p, where κ(p) > 0 for all p. Using standard techniques, we also show that it is NP-hard to approximate the problem within a constant ratio, independent of p.     

Curves on normal surfaces

We study locally Cohen-Macaulay space curves lying on normal surfaces. We prove some theorems on the behaviour of the cohomology functions and initial ideals of such space curves, which give a basic distinction between those curves and curves lying on non-normal surfaces.

     

Separation of polyelectrolyte chain dynamics and dynamics of counterion attachment by EPR spectroscopy

Rotational dynamics and local enrichment of counterions close to polyelectrolyte chains were studied by EPR spectroscopy in solvents of different viscosity. The results confirm previous findings (D. Hinderberger, G. Jeschke, and H. W. Spiess, Macromolecules 2002, 35, 9698) that electrostatic attachment of counterions to the chains is dynamic with lifetimes of contact ion pairs shorter than 1 ns. While in low-viscosity solvents linewidths for a dianionic nitroxide probe and their dependence on polyelectrolyte concentration are dominated by the gradient of local concentration in the vicinity of the chain, they are more strongly influenced by changes in rotational dynamics in a glycerol/water mixture. The slowdown of dynamics at higher viscosity strongly depends on polyelectrolyte concentration, suggesting that the lifetime of the attached state increases. The linewidths of trianionic triarylmethyl probes and of the center line of the nitroxide probes are dominated by local counterion enrichment both at low and high viscosity. Comparison of these linewidths and of the extent to which the lineshapes are non-Lorentzian indicates build-up of larger concentration gradients at higher viscosity.     

Survival of Dipolar Splittings between Equivalent Nuclei in High-Speed MAS-NMR—Interpretation of the 31P Coupling Patterns for Tetraphosphorus Decaoxide

Unexpected splittings in solid-state MAS-NMR spectra can indicate high rather than low local symmetry. A quantitative analysis of the resulting lineshapes provides information about geometry from a different range of space and time averaging than that of X-ray crystallography, as is demonstrated here for tetraphosphorus decaoxide (spectra on the right).     

Application of sensitive hydrogels in chemical and pH sensors

In the present work, pH-sensitive poly(vinyl alcohol)/poly(acrylic acid) (PVA/PAA) blends as well as hydrogels based on poly(N-isopropylacrylamide) (PNIPAAm), which are sensitive to organic solvent concentration in aqueous solutions, were used in silicon micromachined sensors. A sensitivity of approximately 15 mV/pH was obtained for a pH sensor with a 50 μm thick PVA/PAA hydrogel layer in a pH range above the acid exponent of acrylic acid (pK_a=4.7). The output voltage versus pH-value characteristics and the long-term signal stability of hydrogel-based sensors were investigated and the measurement conditions necessary for high signal reproducibility were determined. The influence of the preparation conditions of the hydrogel films on the sensitivity and response time of the chemical and pH sensors is discussed.