Switchable stimulated Raman scattering microscopy with photochromic vibrational probes

Photochromic probes with reversible fluorescence have revolutionized the fields of single molecule spectroscopy and super-resolution microscopy, but lack sufficient chemical specificity. In contrast, Raman probes with stimulated Raman scattering (SRS) microscopy provides superb chemical resolution for super-multiplexed imaging, but are relatively inert. Here we report vibrational photochromism by engineering alkyne tagged diarylethene to realize photo-switchable SRS imaging. The narrow Raman peak of the alkyne group shifts reversibly upon photoisomerization of the conjugated diarylethene when irradiated by ultraviolet (UV) or visible light, yielding “on” or “off” SRS images taken at the photoactive Raman frequency. We demonstrated photo-rewritable patterning and encryption on thin films, painting/erasing of cells with labelled alkyne-diarylethene, as well as pulse-chase experiments of mitochondria diffusion in living cells. The design principle provides potentials for super-resolution microscopy, optical memories and switches with vibrational specificity.

High-resolution terahertz-driven atom probe tomography

Ultrafast control of matter by a strong electromagnetic field on the atomic scale is essential for future investigations and manipulations of ionization dynamics and excitation in solids. Coupling picosecond duration terahertz pulses to metallic nanostructures allows the generation of extremely localized and intense electric fields. Here, using single-cycle terahertz pulses, we demonstrate control over field ion emission from metallic nanotips. The terahertz near field is shown to induce an athermal ultrafast evaporation of surface atoms as ions on the subpicosecond time scale, with the tip acting as a field amplifier. The ultrafast terahertz-ion interaction offers unprecedented control over ultrashort free-ion pulses for imaging, analyzing, and manipulating matter at atomic scales. Here, we demonstrate terahertz atom probe microscopy as a new platform for microscopy with atomic spatial resolution and ultimate chemical resolution.

Two methods for the preparation of sitagliptin phosphate via chemical resolution and asymmetric hydrogenation

Two effective processes have been developed for the preparation of sitagliptin phosphate.

Structure of the Bacterial Ribosome at 2 Å Resolution

Continuing advances in cryo-electron microscopy (cryo-EM) demonstrate the promise it holds for revealing biological structures at chemical resolution, in which noncovalent interactions, RNA and protein modifications, and solvation can be modeled accurately. At present, the best cryo-EM-derived models of the bacterial ribosome are of the large (50S) ribosomal subunit with effective global resolutions of 2.4-2.5 Å, based on map-to-model Fourier shell correlation (FSC). Here we present a model of the E. coli 70S ribosome with an effective global resolution of 2.0 Å, based on maps showcasing unambiguous positioning of residues, their detailed chemical interactions, and chemical modifications. These modifications include the first examples of isopeptide and thioamide backbone substitutions in ribosomal proteins, the former of which is likely conserved in all domains of life. The model also defines extensive solvation of the small (30S) ribosomal subunit for the first time, as well as interactions with A-site and P-site tRNAs, mRNA, and the antibiotic paromomycin. The high quality of the maps now allows a deeper phylogenetic analysis of ribosomal components, and identification of structural conservation to the level of solvation. The maps and models of the bacterial ribosome presented here should enable future structural analysis of the chemical basis for translation, and the development of robust tools for cryo-EM structure modeling and refinement.

Cryogenic OrbiSIMS Localizes Semi-Volatile Molecules in Biological Tissues

OrbiSIMS is a recently developed instrument for label-free imaging of chemicals with micron spatial resolution and high mass resolution. Here we report a cryogenic workflow for OrbiSIMS (Cryo-OrbiSIMS) that improves chemical detection of lipids and other biomolecules in tissues. Cryo-OrbiSIMS decreases ion-beam induced fragmentation, allowing large molecules such as triglycerides to be more reliably identified. It also increases chemical coverage to include biomolecules with intermediate or high vapor pressures, such as free fatty acids and semi-volatile organic compounds (SVOCs). We find that Cryo-OrbiSIMS reveals the hitherto unknown localization patterns of SVOCs with high spatial and chemical resolution in diverse plant, animal and human tissues. We also show that Cryo-OrbiSIMS can be combined with genetic analysis to identify enzymes regulating SVOC metabolism. Cryo-OrbiSIMS is applicable to high resolution imaging of a wide variety of non-volatile and semi-volatile molecules across many areas of biomedicine.

Asymmetric Synthetic Strategies of (R)-(–)-Baclofen: An Antispastic Drug

Baclofen is an antispastic drug used as a muscle relaxant in the treatment of the paroxysmal pain of trigeminal neuralgia, spasticity of the spinal cord and cerebral origin. Baclofen resides biological activity exclusively in its (R)-(–)-enantiomer. In this review, various asymmetric synthetic strategies for (R)-(–)-baclofen are described.1 Introduction2 Resolution Synthetic Approaches2.1 Chemical Resolution2.2 Biocatalytic Resolution3 Asymmetric Desymmetrization3.1 Catalytic Enantioselective Desymmetrization3.2 Enzymatic Desymmetrization4 Chiral Auxiliary Induced Asymmetric Synthesis4.1 Asymmetric Michael Addition4.2 Asymmetric Aldol Addition4.3 Asymmetric Nucleophilic Substitution5 Asymmetric Reduction5.1 Catalytic Asymmetric Hydrogenation5.2 Bioreduction6 Catalytic Asymmetric Conjugate Addition7 Conclusion