A new, mild synthesis of N-sulfonyl ketimines via the palladium-catalyzed isomerization of aziridines

[reaction: see text] A new method for the synthesis of N-tosylketimines via the palladium-catalyzed isomerization of N-tosylaziridines is described. The mild reaction conditions tolerate the presence of a variety of functional groups including ketones, esters, and acetals. The reactions are believed to proceed via the oxidative addition of the aziridine to Pd(0) and represent the first examples of transformations involving Pd(0)-mediated oxidative additions of aziridines that do not proceed through allylpalladium intermediates.     

Improved generation of anti-tumor immunity by antigen dose limitation

Background  

The malignant cells of cutaneous T cell lymphoma (CTCL) display immunogenic peptides derived from the clonal T cell receptor (TCR) providing an attractive model for refinement of anti-tumor immunization methodology. To produce a clinically meaningful anti-tumor response, induction of cytotoxic anti-CTCL cells must be maximized while suppressive T regulatory cells (Treg) should be minimized. We have demonstrated that engulfment of apoptotic CTCL cells by dendritic cells (DC) can lead to either CD8 anti-CTCL responses or immunosuppressive Treg induction. Treg generation is favored when the number of apoptotic cells available for ingestion is high.     

The Synthesis And Chemical Properties Of N-D-Pentopyranosylamines,Derivatives Of Tryptamine And Tyramine.

Abstract

The synthesis and structure of N-D-pentopyranosylamines derived from the amines tiyptamine tyramine and the pentoses D-xylose, D-arabinose and D-lyxose are presented. NMR spectroscopy and mass spectrometry were used to verify the proposed α,β-D-pentopyranosylamine structures.     

Atmospheric plasma treatment of pre‐electrospinning polymer solution: A feasible method to improve electrospinnability

The electrospinnability of polyethylene oxide (PEO) was manipulated by atmospheric plasma treatment of pre‐electrospinning solutions. Conductivity, viscosity, and surface tension of PEO solutions increased after plasma treatment, and the plasma effect remained longer when the solution concentrate increased. Both untreated and treated solutions were then electrospun, and the morphology of the resultant nanofibers was observed by SEM. Atmospheric plasma treatment improved the electrospinnability of PEO solutions and led to less beads and finer diameter distribution in the resultant nanofibers. Additionally, plasma treatment of the pre‐electrospinning solutions affected the crystal structure of resultant nanofibers. These results suggest that atmospheric plasma treatment is a feasible approach to improve the electrospinnability of polymer solutions and can used to control the structure of electrospun nanofibers. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011     

Applying Unconventional Spectroscopies to the Single-Molecule Magnets,Co(PPh3)2X2 (X=Cl,Br, I): Unveiling Magnetic Transitions and Spin-Phonon Coupling

Large separation of magnetic levels and slow relaxation in metal complexes are desirable properties of single-molecule magnets (SMMs). Spin-phonon coupling (interactions of magnetic levels with phonons) is ubiquitous, leading to magnetic relaxation and loss of memory in SMMs and quantum coherence in qubits. Direct observation of magnetic transitions and spin-phonon coupling in molecules is challenging. We have found that far-IR magnetic spectra (FIRMS) of Co(PPh₃)₂X₂ ( Co-X ; X=Cl, Br, I) reveal rarely observed spin-phonon coupling as avoided crossings between magnetic and u-symmetry phonon transitions. Inelastic neutron scattering (INS) gives phonon spectra. Calculations using VASP and phonopy programs gave phonon symmetries and movies. Magnetic transitions among zero-field split (ZFS) levels of the S=3/2 electronic ground state were probed by INS, high-frequency and -field EPR (HFEPR), FIRMS, and frequency-domain FT terahertz EPR (FD-FT THz-EPR), giving magnetic excitation spectra and determining ZFS parameters (D, E) and g values. Ligand-field theory (LFT) was used to analyze earlier electronic absorption spectra and give calculated ZFS parameters matching those from the experiments. DFT calculations also gave spin densities in Co-X , showing that the larger Co(II) spin density in a molecule, the larger its ZFS magnitude. The current work reveals dynamics of magnetic and phonon excitations in SMMs. Studies of such couplings in the future would help to understand how spin-phonon coupling may lead to magnetic relaxation and develop guidance to control such coupling.     

Towards the stable chelation of radium for biomedical applications with an 18-membered macrocyclic ligand

Targeted alpha therapy is an emerging strategy for the treatment of disseminated cancer. [²²³Ra]RaCl₂ is the only clinically approved alpha particle-emitting drug, and it is used to treat castrate-resistant prostate cancer bone metastases, to which [²²³Ra]Ra²⁺ localizes. To specifically direct [²²³Ra]Ra²⁺ to non-osseous disease sites, chelation and conjugation to a cancer-targeting moiety is necessary. Although previous efforts to stably chelate [²²³Ra]Ra²⁺ for this purpose have had limited success, here we report a biologically stable radiocomplex with the 18-membered macrocyclic chelator macropa. Quantitative labeling of macropa with [²²³Ra]Ra²⁺ was accomplished within 5 min at room temperature with a radiolabeling efficiency of >95%, representing a significant advancement over conventional chelators such as DOTA and EDTA, which were unable to completely complex [²²³Ra]Ra²⁺ under these conditions. [²²³Ra][Ra(macropa)] was highly stable in human serum and exhibited dramatically reduced bone and spleen uptake in mice in comparison to bone-targeted [²²³Ra]RaCl₂, signifying that [²²³Ra][Ra(macropa)] remains intact in vivo. Upon conjugation of macropa to a single amino acid β-alanine as well as to the prostate-specific membrane antigen-targeting peptide DUPA, both constructs retained high affinity for ²²³Ra, complexing >95% of Ra²⁺ in solution. Furthermore, [²²³Ra][Ra(macropa-β-alanine)] was rapidly cleared from mice and showed low ²²³Ra bone absorption, indicating that this conjugate is stable under biological conditions. Unexpectedly, this stability was lost upon conjugation of macropa to DUPA, which suggests a role of targeting vectors in complex stability in vivo for this system. Nonetheless, our successful demonstration of efficient radiolabeling of the β-alanine conjugate with ²²³Ra and its subsequent stability in vivo establishes for the first time the possibility of delivering [²²³Ra]Ra²⁺ to metastases outside of the bone using functionalized chelators, marking a significant expansion of the therapeutic utility of this radiometal in the clinic.

The therapeutic alpha-emitter ²²³Ra can be stably complexed in vivo, creating opportunities for the development of targeted radiopharmaceutical agents with this radionuclide.