Fast and Reliable Automated Synthesis of RNA and Partially 2′-O- Protected Precursors (`Caged RNA') Based on Two Novel,Orthogonal 2′-O-Protecting Groups,Preliminary Communication

Two sets of RNA phosphoramidites, carrying the (fluoride-labile) 2′-O-[(triisopropylsilyl)oxy]methyl (=tom) group and the (photolabile) [(R)-1-(2-nitrophenyl)ethoxy]methyl (=(R)-npeom) group, were prepared (see 1 – 4 and 5 – 8 , resp.). The two protecting groups were completely orthogonal to each other. Three ribozyme-substrate constructs, protected each by a (R)-npeom group, were synthesized; on photolysis, efficient cleavage of this remaining protecting group occurred (Scheme 3). It could be demonstrated that the presence of one (R)-npeom group within a RNA strand has only a minor influence on the pairing properties of corresponding duplexes.     

Mechanistic Insights into the Interface‐Directed Transformation of Thiols into Disulfides and Molecular Hydrogen by Visible‐Light Irradiation of Quantum Dots

Quantum dots (QDs) offer new and versatile ways to harvest light energy. However, there are few examples involving the utilization of QDs in organic synthesis. Visible‐light irradiation of CdSe QDs was found to result in virtually quantitative coupling of a variety of thiols to give disulfides and H₂ without the need for sacrificial reagents or external oxidants. The addition of small amounts of nickel(II) salts dramatically improved the efficiency and conversion through facilitating the formation of hydrogen atoms, thereby leading to faster regeneration of the ground‐state QDs. Mechanistic studies reveal that the coupling reaction occurs on the QD surfaces rather than in solution and offer a blueprint for how these QDs may be used in other photocatalytic applications. Because no sacrificial agent or oxidant is necessary and the catalyst is reusable, this method may be useful for the formation of disulfide bonds in proteins as well as in other systems sensitive to the presence of oxidants.     

Improved sensitivity proteomics by postharvest alkylation and radioactive labelling of proteins

We describe approaches to improve the detection of proteins by postharvest alkylation and subsequent radioactive labeling with either [3H]iodoacetamide or 125I. Database protein sequence analysis suggested that cysteine is not suitable for detection of the entire proteome, but that cysteine alkylating reagents can increase the number of proteins able to be detected by iodination chemistry. Proteins were alkylated with beta-(4-hydroxyphenyl)ethyl iodoacetamide, or with 1,5-l-AEDANS (the Hudson Weber reagent). Subsequent iodination using the Iodo-Gen system was found to be most efficient. The enhanced sensitivity obtainable by using these approaches is expected to be sufficient for visualization of the lowest copy number proteins from human cells, such as from clinical samples. However, we argue that significantly improved methods of protein separation will be necessary to resolve the large number of proteins expected to be detectable with this sensitivity.     

Spectroscopic characterization of molybdenum dinitrogen complexes containing a combination of di- and triphosphine coligands: 31P NMR analysis of five-spin systems

The three molybdenum-N2 complexes [Mo(N2)(dpepp)(depe)] (1), [Mo(N2)(dpepp)(dppe)] (2), and [Mo(N2)(dpepp)(1,2-dppp)] (3), all of which contain a combination of a bi- and a tridentate phosphine ligand, were prepared and investigated by vibrational and (31)P NMR spectroscopy. As a tridentate ligand bis(2-diphenylphosphinoethyl)phenylphosphine (dpepp) has been employed. The three different bidentate ligands are 1,2-bis(diethylphosphino)ethane (depe), 1,2-bis(diphenylphosphino)ethane (dppe), and R-(+)-1,2-bis(diphenylphosphino)propane (1,2-dppp). N-N as well as metal-N vibrations of 1-3 are identified and interpreted in terms of the geometric and electronic structures of the complexes. (31)P NMR spectra are recorded and fully analyzed. Moreover, correlation spectroscopy (COSY)-45 measurements are performed to determine the relative signs of coupling constants. Special attention is directed to a detection of different isomers and their (31)P NMR, as well as vibrational spectroscopic properties. The implications of the results for the area of synthetic nitrogen fixation with phosphine complexes are discussed.     

A Chemical Proteomic Strategy Reveals Inhibitors of Lipoate Salvage in Bacteria and Parasites

The development of novel anti-infectives requires unprecedented strategies targeting pathways which are solely present in pathogens but absent in humans. Following this principle, we developed inhibitors of lipoic acid ( LA ) salvage, a crucial pathway for the survival of LA auxotrophic bacteria and parasites but non-essential in human cells. An LA -based probe was selectively transferred onto substrate proteins via lipoate protein ligase (LPL) in intact cells, and their binding sites were determined by mass spectrometry. Probe labeling served as a proxy of LPL activity, enabling in situ screenings for cell-permeable LPL inhibitors. Profiling a focused compound library revealed two substrate analogs ( LAMe and C3 ) as inhibitors, which were further validated by binding studies and co-crystallography. Importantly, LAMe exhibited low toxicity in human cells and achieved killing of Plasmodium falciparum in erythrocytes with an EC₅₀ value of 15 μM, making it the most effective LPL inhibitor reported to date.     

Phosphino-Phosphination Reactions: Frustrated Lewis Pair Reactivity of Phosphino-Phosphonium Cations with Alkynes

The phosphino-phosphonium cations of the form [R₃PPR′₂]⁺ are labile and provide access to the constituent Lewis acidic and Lewis basic fragments. This permits frustrated Lewis pair-type addition reactions to alkynes, affording unprecedented phosphino-phosphination reactions and giving cations of the form [cis-R₃PCHC(R′′)PR′₂]⁺. This reactivity is further adapted to prepare several examples of a rare class of dissymmetric cis-olefin-linked bidentate phosphines.     

Quantitative Depth Profiling Using Online-Laser Ablation of Solid Samples in Liquid (LASIL) to Investigate the Oxidation Behavior of Transition Metal Borides

The increased demand for sustainability requires, among others, the development of new materials with enhanced corrosion resistance. Transition metal diborides are exceptional candidates, as they exhibit fascinating mechanical and thermal properties. However, at elevated temperatures and oxidizing atmospheres, their use is limited due to the fact of their inadequate oxidation resistance. Recently, it was found that chromium diboride doped with silicon can overcome this limitation. Further improvement of this protective coating requires detailed knowledge regarding the composition of the forming oxide layer and the change in the composition of the remaining thin film. In this work, an analytical method for the quantitative measurement of depth profiles without using matrix-matched reference materials was developed. Using this approach, based on the recently introduced online-LASIL technique, it was possible to achieve a depth resolution of 240 nm. A further decrease in the ablation rate is possible but demands a more sensitive detection of silicon. Two chromium diboride samples with different Si contents suffering an oxidation treatment were used to demonstrate the capabilities of this technique. The concentration profiles resembled the pathway of the formed oxidation layers as monitored with transmission electron microscopy. The stoichiometry of the oxidation layers differed strongly between the samples, suggesting different processes were taking place. The validity of the LASIL results was cross-checked with several other analytical techniques.     

Non-affine structural evolution of soft colloidal crystalline latex films under stretching as observed via synchrotron X-ray scattering

A polymer dispersion consisting of soft latex spheres with a diameter of 135 nm was used to produce a crystalline film with face-centered cubic (fcc) packing of the spheres. Different from conventional small-molecule and hard-sphere colloidal crystals, the crystalline latex film in the present case is soft (i.e., easily deformable). The structural evolution of this soft colloidal latex film under stretching was investigated by in-situ synchrotron ultra-small-angle X-ray scattering. The film exhibits polycrystalline scattering behavior corresponding to fcc structure. Stretching results not only in a large deformation of the crystallographic structure but also in considerable nonaffine deformation at high draw ratios. The unexpected nonaffine deformation was attributed to slippage between rows of particles and crystalline grain boundaries. The crystalline structure remains intact even at high deformation, suggesting that directional anisotropic colloidal crystallites can be easily produced.     

PLD-assisted VLS growth of aligned ferrite nanorods, nanowires, and nanobelts-synthesis, and properties

We report here a systematic synthesis and characterization of aligned alpha-Fe2O3 (hematite), epsilon-Fe2O3, and Fe3O4 (magnetite) nanorods, nanobelts, and nanowires on alumina substrates using a pulsed laser deposition (PLD) method. The presence of spherical gold catalyst particles at the tips of the nanostructures indicates selective growth via the vapor-liquid-solid (VLS) mechanism. Through a series of experiments, we have produced a primitive "phase diagram" for growing these structures based on several designed pressure and temperature parameters. Transmission electron microscopy (TEM) analysis has shown that the rods, wires, and belts are single-crystalline and grow along <111>m or <110>h directions. X-ray diffraction (XRD) measurements confirm phase and structural analysis. Superconducting quantum interference device (SQUID) measurements show that the iron oxide structures exhibit interesting magnetic behavior, particularly at room temperature. This work is the first known report of magnetite 1D nanostructure growth via the vapor-liquid-solid (VLS) mechanism without using a template, as well as the first known synthesis of long epsilon-Fe2O3 nanobelts and nanowires.     

Phosphonium-borate zwitterions, anionic phosphines, and dianionic phosphonium-dialkoxides via tetrahydrofuran ring-opening reactions

Sterically demanding secondary phosphines and phosphides react with (THF)B(C(6)F(5))(3) (THF = tetrahydrofuran) to give the THF ring-opened compounds [R(2)PHC(4)H(8)OB(C(6)F(5))(3)] and [Mes(2)PC(4)H(8)OB(C(6)F(5))(3)Li(THF)(2)] (Mes = C(6)H(2)Me-2,4,6). These reactions also occur consecutively to give the double THF ring-opened compounds [Mes(2)P(C(4)H(8)OB(C(6)F(5))(3))(2)][Li(THF)(4)] and [t-Bu(2)P(C(4)H(8)OB(C(6)F(5))(3))(2)Li].