Inducing axial chirality in a "Geländer" oligomer by length mismatch of the oligomer strands.

Helical molecules are not only esthetically appealing due to their structural beauty, they also display unique physical properties as a result of their chirality. We describe herein a new approach to "Geländer" oligomers by interlinking two oligomer strands of different length. To compensate for the dimensional mismatch, the longer oligo(benzyl ether) oligomer wraps around the oligophenyl backbone. The new "Geländer" oligomer 1 was assembled in a sequence of functional-group transformations and cross-coupling steps followed by final cyclizations based on nucleophilic substitution reactions, and was fully characterized, including X-ray diffraction analysis. The isolation of pure enantiomers enabled the racemization process to be studied by circular dichroism spectroscopy.

A novel self-lipid antigen targets human T cells against CD1c(+) leukemias.

T cells that recognize self-lipids presented by CD1c are frequent in the peripheral blood of healthy individuals and kill transformed hematopoietic cells, but little is known about their antigen specificity and potential antileukemia effects. We report that CD1c self-reactive T cells recognize a novel class of self-lipids, identified as methyl-lysophosphatidic acids (mLPAs), which are accumulated in leukemia cells. Primary acute myeloid and B cell acute leukemia blasts express CD1 molecules. mLPA-specific T cells efficiently kill CD1c(+) acute leukemia cells, poorly recognize nontransformed CD1c-expressing cells, and protect immunodeficient mice against CD1c(+) human leukemia cells. The identification of immunogenic self-lipid antigens accumulated in leukemia cells and the observed leukemia control by lipid-specific T cells in vivo provide a new conceptual framework for leukemia immune surveillance and possible immunotherapy.

Atropisomerization of di-para-substituted propyl-bridged biphenyl cyclophanes.

The influence of electron donors and electron acceptors of variable strength in the 4 and 4' position of 2 and 2' propyl-bridged axial chiral biphenyl cyclophanes on their atropisomerization process was studied. Estimated free energies ΔG(‡)(T) of the rotation around the central biphenyl bond which were obtained from (1)H-NMR coalescence measurements were correlated to the Hammett parameters σ(p) as a measure for electron donor and acceptor strength. It is demonstrated that the resulting nice linear correlation is mainly based on the influence of the different substituents on the π-system of the biphenyl cyclophanes. By lineshape analysis the rate constants were calculated and by the use of the Eyring equation the enthalpic and entropic contributions were evaluated. Density functional theory calculations show a planar transition state of the isomerization process and the calculated energy barriers based on this reaction mechanism are in good agreement with the experimentally obtained free energies.

Racemisation dynamics of torsion angle restricted biphenyl push-pull cyclophanes.

The thermodynamics of the atropisomerisation of torsion angle restricted, axial chiral biphenyl-based push-pull cyclophanes were studied. Using (1)H NMR coalescence measurements the rotation barrier around the central C-C bond was determined to be 50 kJ mol(-1) for the propyl-bridged biphenyl derivative 1b, displaying only a negligible solvent dependence. By protonation of the piperidinyl nitrogen as electron donor, the free energy ΔG(‡)(T) of the rotation barrier increased, indicating that the tendency of the push-pull system to planarise may be considered as a driving force for the atropisomerisation. For the more restricted butyl-bridged cyclophane 1c a rotation barrier of ΔG(‡)(T) = 90 kJ mol(-1) was measured using dynamic chromatography. The difference in the free energy of rotation around the central C-C bond probably reflects the crowdedness of the transition states.