Determination of the impurity profile of ethyl-2-(4-[(5R)-3[4-(methoxycarboxamidoiminomethyl)-phenyl]-2- oxo-5-oxazolidinylmethyl]-1-piperazinyl) acetate, citrate, a highly active platelet aggregation inhibitor, by liquid chromatography-mass spectrometry.

Ethyl-2-(4-[(5R)-3-[4-(methoxycarboxamidoiminomethyl)-phenyl] -2-oxo-5-oxazolidinylmethyl]-1-piperazinyl) acetate, a glycoprotein IIb/IIIa antagonist, is a drug substance of the oxazolidinone type from Merck's research to be developed for the chronic oral treatment of thrombotic disorders. For the separation of the byproducts in the bulk drug substance, a reversed-phase HPLC gradient separation was developed. The eluent consisting of a nonvolatile phosphate buffer system had to be changed to a volatile acetate buffer system in order to perform on-line LC-MS coupling.With a triple quadrupole system it was possible to characterize most of the unknown byproducts occuring during synthesis and during scale-up to kg amounts of the bulk drug substance.     

The order-interval hypergraph of a finite poset and the König property

We study the hypergraph H(P) whose vertices are the points of a finite poset and whose edges are the maximal intervals in P (i.e. sets of the form I = {{v ε P: p ν q}}, p minimal, q maximal). We mention resp. show that the problems of the determination of the independence number , the point covering number τ, the matching number v and the edge covering number p are NP-complete. For interval orders we describe polynomial algorithms and prove the König property (v = τ) and the dual König property (a = p). Finally we show that the (dual) König property is preserved by product.     

Preparation of relativistic 7Li+ ion beams for precision experiments at storage rings

Heavy ion storage rings allow for tests of the structure of local space time via the Doppler effect. At the TSR/Heidelberg an experiment with high resolution laser spectroscopy at ⁷Li⁺ is performed. To gain the maximum resolution for saturation spectroscopy new methods of relativistic ion beam preparation and diagnostics have been developed. The laser cooling of the beam allows for precision determination of the mean velocity of the ions. A novel phase synchronous detection scheme, ultimately sensitive to single ions, gives insights into the cooling mechanism and dynamics. With an additional synchronous excitation scheme systematic uncertainties of the test experiment can be drastically reduced. After separation of the ground state ions from the triplet states of ⁷Li⁺ by the combination of laser and electron cooling, a bunched and cooled ensemble of fast moving high precision clocks with minimized perturbations by space charge effects and intra beam scattering is available. This revised version was published online in August 2006 with corrections to the Cover Date.     

Temperature resolved X-ray diffraction as a tool of thermal analysis

Time and temperature resolved X-ray diffraction was used for thermal analysis. Series of diffraction patterns were measured, while the samples are heated/cooled stepwise or isothermally with freely selectable temperature programs.The method was applied for the investigation of the phase transitions of ammonium nitrate and HMX (1,3,5,7-tetranitro-1,3,5,7-tetraaza-cyclooctane), when the identification of phases was required. Its capability in the field of kinetics is demonstrated with the isothermal investigation of the solid state reaction of ammonium nitrate with copper oxide and the non-isothermal investigation of the high temperature corrosion of nickel, which was performed by means of a difference procedure. For obtaining structural details peak fitting and Rietveld refinement were applied for the investigation of ammonium nitrate and HMX.We are indebted to Mr. K. O. Hartmann, Mr. H. Fietzek and Mr. H. G. Farr for their assistance during the measurements and for the maintenance of the measuring systems.     

Self-assembly of monatomic complex crystals and quasicrystals with a double-well interaction potential

For the study of crystal formation and dynamics, we introduce a simple two-dimensional monatomic model system with a parametrized interaction potential. We find in molecular dynamics simulations that a surprising variety of crystals, a decagonal, and a dodecagonal quasicrystal are self-assembled. In the case of the quasicrystals, the particles reorder by phason flips at elevated temperatures. During annealing, the entropically stabilized decagonal quasicrystal undergoes a reversible phase transition at 65% of the melting temperature into an approximant, which is monitored by the rotation of the de Bruijn surface in hyperspace.     

Single-shot gradient-assisted photon echo electronic spectroscopy

Two-dimensional electronic spectroscopy (2D ES) maps the electronic structure of complex systems on a femtosecond time scale. While analogous to multidimensional NMR spectroscopy, 2D optical spectroscopy differs significantly in its implementation. Yet, 2D Fourier spectroscopies still require point-by-point sampling of the time delay between two pulses responsible for creating quantum coherence among states. Unlike NMR, achieving the requisite phase stability at optical frequencies between these pulse pairs remains experimentally challenging. Nonetheless, 2D optical spectroscopy has been successfully demonstrated by combining passive and active phase stabilization along with precise control of optical delays and long-term temperature stability, although the widespread adoption of 2D ES has been significantly hampered by these technical challenges. Here, we exploit an analogy to magnetic resonance imaging (MRI) to demonstrate a single-shot method capable of acquiring the entire 2D spectrum in a single laser shot using only conventional optics. Unlike point-by-point sampling protocols typically used to record 2D spectra, this method, which we call GRadient-Assisted Photon Echo (GRAPE) spectroscopy, largely eliminates phase errors while reducing the acquisition time by orders of magnitude. By incorporating a spatiotemporal encoding of the nonlinear polarization along the excitation frequency axis of the 2D spectrum, GRAPE spectroscopy achieves no loss in signal while simultaneously reducing overall noise. Here, we describe the principles of GRAPE spectroscopy and discuss associated experimental considerations.     

Quantitative evaluation of mechanosensing of cells on dynamically tunable hydrogels

Thin hydrogel films based on an ABA triblock copolymer gelator [where A is pH-sensitive poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) and B is biocompatible poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC)] were used as a stimulus-responsive substrate that allows fine adjustment of the mechanical environment experienced by mouse myoblast cells. The hydrogel film elasticity could be reversibly modulated by a factor of 40 via careful pH adjustment without adversely affecting cell viability. Myoblast cells exhibited pronounced stress fiber formation and flattening on increasing the hydrogel elasticity. As a new tool to evaluate the strength of cell adhesion, we combined a picosecond laser with an inverted microscope and utilized the strong shock wave created by the laser pulse to determine the critical pressure required for cell detachment. Furthermore, we demonstrate that an abrupt jump in the hydrogel elasticity can be utilized to monitor how cells adapt their morphology to changes in their mechanical environment.