Asymmetric synthesis of highly substituted azapolycyclic compounds via 2-alkenyl sulfoximines: potential scaffolds for peptide mimetics

The application of metalated, enantiomerically pure acyclic and cyclic 2-alkenyl sulfoximines for the synthesis of highly substituted aza(poly)cyclic ring systems is described. The method relies on a one-pot combination of a reagent-controlled allyl transfer reaction to alpha- or beta-amino aldehydes, followed by a Michael-type cyclization of the intermediate vinyl sulfoximines generated in the first step. The sulfur-free target compounds are preferentially obtained by samarium iodide treatment of the sulfonimidoyl substituted heterocycles. In addition to this methodological work, initial results on the biological activity of selected examples are reported. Furthermore, a concept for the transformation of peptidic lead structures into non-peptide mimetics is described, and the relevance of the new approach to highly substituted azaheterocycles in this context is discussed.     

Mass spectrometry meets chip technology: a new proteomic tool in cancer research?

DNA chip technologies are the most exiting genomic tools, which were developed within the last few years. It is, however, evident that knowledge of the gene sequence or the quantity of gene expression is not sufficient to predict the biological nature and function of a protein. This can be particularly important in cancer research where post-translational modifications of a protein can specifically contribute to the disease. To address this problem, several proteomic tools have been developed. Currently the most widely used proteomic tool is two-dimensional protein gel electrophoresis (2-DE), which can display protein expression patterns to a high degree of resolution. As an alternative to 2-DE, a preliminary study using a new technique was employed to generate protein expression patterns from whole tissue extracts. Surface-enhanced laser desorption/ionization (SELDI) allows the retention of proteins on a solid-phase chromatographic surface (ProteinChip Array) with direct detection of retained proteins by time of flight-mass spectrometry (TOF-MS). Using this system, we analyzed eight cases of renal cell carcinoma (RCC) including normal, peripheral and central tumor tissue as well as four microdissected cases of cervical intraepithelial neoplasia (CIN) and three microdissected cases of cervix uteri carcinoma. Differentially expressed proteins were found by comparing the protein expression patterns generated using SELDI-based TOF-MS of tumor tissue with normal and neoplastic tissue, respectively. By applying this fast and powerful ProteinChip array technology it becomes possible to investigate complex changes at the protein level in cancer associated with tumor development and progression.     

Synthesen und Strukturen donorstabilisierter Aluminiumdihalogenide

Syntheses and Structures of Donor-stabilized Aluminiumdihalides During the disproportionation of metastable AlX-solutions (X = Cl, Br, I) donor-stabilized aluminiumdihalides are formed. X-ray diffraction analysis shows that all of them exhibit a dimeric structure DoX₂Al–AlX₂Do (Do = donor-molecule). The Al–Al-bond length which is significantly shorter than in the organometallic R₂Al–AlR₂-species is strongly influenced by the donor-molecule as well as by the halogen ligands. With the help of quantum chemical calculations a deeper understanding of this bonding situation is obtained.     

Energy loss of deuterons in 3He gas: a threshold effect

The energy loss of deuterons in ³He gas was measured at E _d = 15 to 100 keV using the ³He pressure dependence of the ³He(d,p)⁴He cross-section at a given incident energy. At the highest energies, the observed energy loss is in good agreement with a standard compilation. However, with decreasing energy the experimental values drop steadily below the theoretical values and near E _d = 18 keV they drop sharply (within 1 keV) reaching the domain of nuclear stopping power. This threshold behavior is due to the minimum 1s → 2s electron excitation of the He target atoms, i.e. it is a quantum effect. Some consequences are discussed.     

Development of Bicyclo[3.1.0]hexane-Based A3 Receptor Ligands: Closing the Gaps in the Structure–Affinity Relationships

The adenosine A₃ receptor is a promising target for treating and diagnosing inflammation and cancer. In this paper, a series of bicyclo[3.1.0]hexane-based nucleosides was synthesized and evaluated for their P1 receptor affinities in radioligand binding studies. The study focused on modifications at 1-, 2-, and 6-positions of the purine ring and variations of the 5′-position at the bicyclo[3.1.0]hexane moiety, closing existing gaps in the structure–affinity relationships. The most potent derivative 30 displayed moderate A₃AR affinity (Ki of 0.38 μM) and high A₃R selectivity. A subset of compounds varied at 5′-position was further evaluated in functional P2Y₁R assays, displaying no off-target activity.     

Electronic excitations during grazing scattering of hydrogen atoms on KI(001) and LiF(001) surfaces

The energy loss of hydrogen atoms with energies of 400 eV and 1 keV is studied in coincidence with the number of emitted electrons during grazing scattering from atomically clean and flat KI(001) and LiF(001) surfaces. The energy loss spectra for specific numbers of emitted electrons are analyzed in terms of a binary interaction model based on the formation of transient negative ions via local capture of valence band electrons from anion sites. Based on computer simulations we derive for this interaction scenario probabilities for the production of surface excitons, for electron loss to the conduction band of KI, for emission of electrons, and for formation of negative hydrogen ions. The pronounced differences of data obtained for the two surfaces are attributed to the different electronic structures of KI and LiF.     

14.5GHz紧凑型、低成本、全永磁ECR离子源

A compact 14.5GHz electron cyclotron resonance (ECR) ion source for the production of slow, multiply charged ions has been constructed,with the plasma-confining magnetic field produced exclusively by permanent magnets.Microwave power of up to 175W in the frequency range from 12.75 to 14.SGHz is transmitted from ground potential via a PTFE window into the water-cooled plasma chamber which can be equipped with an aluminum liner.The waveguide coupling system serves also as biased electrode,and two remotely-controlled gas inlet valves connected via an insulating break permit plasma operation in the gas- mixing mode.A triode extraction system sustains ion acceleration voltages between 1kV and 10kV.The ECR ion source is fully computer-controlled and can be remotely operated from any desired location via Ethernet.     

Intensity dependence of photoassociation in a quantum degenerate atomic gas

We have measured the intensity dependent rate and frequency shift of a photoassociation transition in a quantum degenerate gas of 7Li. The rate increases linearly with photoassociation laser intensity for low intensities, whereas saturation is observed at higher intensities. The measured rates and shifts agree reasonably well with theory within the estimated systematic uncertainties. Several theoretically predicted saturation mechanisms are discussed, but a theory in which saturation arises because of quantum mechanical unitarity agrees well with the data.     

Superconducting transition in polysulfur nitride as a function of crystal quality

The superconducting transition temperature in polysulfur nitride crystals of various quality appears invariant between 0.26 and 0.28°K, but the completeness of the transition varies from sample to sample. A residual resistance remains in bulk samples which reflects the density of fiber segment junctions.