One Way Traffic: Base-to-Backbone Hole Transfer in Nucleoside Phosphorodithioate

The directionality of the hole-transfer processes between DNA backbone and base was investigated by using phosphorodithioate [P(S⁻)=S] components. ESR spectroscopy in homogeneous frozen aqueous solutions and pulse radiolysis in aqueous solution at ambient temperature confirmed initial formation of G^.+-P(S⁻)=S. The ionization potential of G-P(S⁻)=S was calculated to be slightly lower than that of guanine in 5′-dGMP. Subsequent thermally activated hole transfer from G^.+ to P(S⁻)=S led to dithiyl radical (P-2S^.) formation on the μs timescale. In parallel, ESR spectroscopy, pulse radiolysis, and density functional theory (DFT) calculations confirmed P-2S^. formation in an abasic phosphorodithioate model compound. ESR investigations at low temperatures and higher G-P(S⁻)=S concentrations showed a bimolecular conversion of P-2S^. to the σ²-σ*¹-bonded dimer anion radical [-P-2S 2S-P-]⁻ [ΔG (150 K, DFT)=−7.2 kcal mol⁻¹]. However, [-P-2S 2S-P-]⁻ formation was not observed by pulse radiolysis [ΔG° (298 K, DFT)=−1.4 kcal mol⁻¹]. Neither P-2S^. nor [-P-2S 2S-P-]⁻ oxidized guanine base; only base-to-backbone hole transfer occurs in phosphorodithioate.     

Time Window Expansion for HDX Analysis of an Intrinsically Disordered Protein

Application of typical HDX methods to examine intrinsically disordered proteins (IDP), proteins that are natively unstructured and highly dynamic at physiological pH, is limited because of the rapid exchange of unprotected amide hydrogens with solvent. The exchange rates of these fast exchanging amides are usually faster than the shortest time scale (10 s) employed in typical automated HDX-MS experiments. Considering the functional importance of IDPs and their association with many diseases, it is valuable to develop methods that allow the study of solution dynamics of these proteins as well as the ability to probe the interaction of IDPs with their wide range of binding partners. Here, we report the application of time window expansion to the millisecond range by altering the on-exchange pH of the HDX experiment to study a well-characterized IDP; the activation domain of the nuclear receptor coactivator, peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α). This method enabled mapping the regions of PGC-1α that are stabilized upon binding the ligand binding domain (LBD) of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ). We further demonstrate the method’s applicability to other binding partners of the IDP PGC-1α and pave the way for characterizing many other biologically important ID proteins.

First Synthesis of 1,3-Alternate 25,27-Dialkyloxy-5,17-diarylcalix[4]arenes-crown-6 as New Cesium Selective Extractants by Suzuki Cross-coupling Reaction

The synthesis of new 25,27-dialkyloxy-5,17-diarylcalix[4]arenes-crown-6 1a–f in 1,3-alternate conformation by Suzuki cross-coupling reaction is reported. Their conformation was determined using ¹H, ¹³C, 2D NMR and ROESY analysis, and X-ray crystallography. Extraction experiments using a two-phase solvent method involving sodium, potassium or cesium picrate showed good extraction of the cesium cation. The X-ray crystal structures of 1,3-alternate 25,27-dipropoxy-5,17-diphenylcalix[4]arene-crown-6 ether 1a and its cesium picrate complex were established. Solid-state data were used to determine the complexation behavior of these new ligands. The efficiency of calixarenes 1a–f for cesium ion extraction could be ascribed to the rigidity and flatness linkages caused by the aryl groups at the lower rim of the aromatic moieties in the calixarene skeleton. In addition, the introduction of these aromatic moieties in positions 5 and 17 enhanced the solubility of the metal complexes in organic media.     

Sterically congested macrobicycles with heteroatomic bridgehead functionality

A series of cyclophanes composed of two triarylelement caps linked by two-atom bridges has been synthesized. The bridgehead functional groups include phosphines in combination with amines, hydrosilanes, methylsilanes, and ethoxysilanes. Computational studies accurately predicted that when the bridgehead substituents are small (lone pairs or protons), an in_,in bridgehead stereochemistry is strongly favored, but larger bridgehead substituents favor the formations of in_,out stereoisomers. The X-ray structures, spectra, and reactivity of these compounds are discussed, as well as the resolution of one of the cyclophanes into pure enantiomers.     

Studies on pyrrolidones. Reactivity of β-enaminoesters derived from pyroglutamic acid. Synthesis of methyl cyano[l-methyl-5-(5-methyl[1,3,4]oxadiazol-2-yl)pyrrolidin-2-ylidene]acetate

The 5-methoxycarbonyl group of β-enaminoesters derived from methyl pyroglutamate was transformed into acids, amides and 1,3,4-oxadiazole.     

Microwave-Assisted Desulfation of the Hemolytic Saponins Extracted from Holothuria scabra Viscera

Saponins are plant and marine animal specific metabolites that are commonly considered as molecular vectors for chemical defenses against unicellular and pluricellular organisms. Their toxicity is attributed to their membranolytic properties. Modifying the molecular structures of saponins by quantitative and selective chemical reactions is increasingly considered to tune the biological properties of these molecules (i) to prepare congeners with specific activities for biomedical applications and (ii) to afford experimental data related to their structure–activity relationship. In the present study, we focused on the sulfated saponins contained in the viscera of Holothuria scabra, a sea cucumber present in the Indian Ocean and abundantly consumed on the Asian food market. Using mass spectrometry, we first qualitatively and quantitatively assessed the saponin content within the viscera of H. scabra. We detected 26 sulfated saponins presenting 5 different elemental compositions. Microwave activation under alkaline conditions in aqueous solutions was developed and optimized to quantitatively and specifically induce the desulfation of the natural saponins, by a specific loss of H₂SO₄. By comparing the hemolytic activities of the natural and desulfated extracts, we clearly identified the sulfate function as highly responsible for the saponin toxicity.     

Variability in the Formation and Framework Polymorphism of Metal-organic Frameworks based on Yttrium(III) and the Bifunctional Organic Linker 2,5-Dihydroxyterephthalic Acid

Depending on the solvothermal reaction conditions, we obtained three different metal-organic frameworks with yttrium(III) as metal component and 2,5-dihdyroxyterepthalic acid (H₄dhtp) as bifunctional organic linker: Y₂(H₂dhtp)₃(dmf)₄ · (dmf)₂ (CPO-29) contains dinuclear, paddle-wheel like inorganic secondary building units (SBUs) connected by the organic linker to a network with α-Po topology, while Y₂(H₂dhtp)(dhtp)(dmf)₂ (CPO-30) and Y₂(H₂dhtp)(dhtp)(dmf)₂(H₂O)₂ · (H₂O)₄ (CPO-31) contain one-dimensional inorganic SBUs that differ in how the half- and fully deprotonated ligands are connected to and arranged around them. Only the carboxylic acid groups of the organic linker are deprotonated in CPO-29, while CPO-30 and CPO-31 contain both 2,5-dihydroxyterephthalate (H₂dhtp^2–) linkers and fully deprotonated 2,5-dioxidoterephthalate (dhtp^4–) linkers. All three compounds contain large volumes filled with solvent, but we were able to demonstrate permanence of porosity only for CPO-30. Variable temperature powder X-ray diffraction reveals that CPO-29 and CPO-31 undergo discontinuous phase transitions upon heating, and the flexibility of the framework structure indicated by these might be the reason for the inability to access the pore volume. Desolvated CPO-30 and CPO-31 are polymorphs, whose network structures differ in whether the H₂dhtp^2– and dhtp^4– linkers are located in cis or trans arrangement around the inorganic SBU.     

Effects of brain polarization on reaction times and pinch force in chronic stroke

Background  

Previous studies showed that anodal transcranial DC stimulation (tDCS) applied to the primary motor cortex of the affected hemisphere (M1_{affected hemisphere}) after subcortical stroke transiently improves performance of complex tasks that mimic activities of daily living (ADL). It is not known if relatively simpler motor tasks are similarly affected. Here we tested the effects of tDCS on pinch force (PF) and simple reaction time (RT) tasks in patients with chronic stroke in a double-blind cross-over Sham-controlled experimental design.     

Surface Modified Single Molecules Free-Diffusion Evidenced by Fluorescence Correlation Spectroscopy

We report on the free diffusion of single molecule near an interface studied using fluorescence correlation spectroscopy. In particular, we show that the chemical nature of the substrate may modify the free diffusion of a widely used molecule (rhodamine 6G), thus inducing unexpected effects in fluorescence correlation spectroscopy measurements. Our results show a strong influence, up to a few micrometer from the interface, of the surface polarity. This effect is assessed through the relative weight of the two dimensions diffusion process observed close to the surface. Our results are discussed in terms of competition between surface-solvent, solvent-molecule and molecule-surface specific interactions.     

On-Surface Synthesis and Characterization of Acene-Based Nanoribbons Incorporating Four-Membered Rings

A bottom up method for the synthesis of unique tetracene-based nanoribbons, which incorporate cyclobutadiene moieties as linkers between the acene segments, is reported. These structures were achieved through the formal [2+2] cycloaddition reaction of ortho-functionalized tetracene precursor monomers. The formation mechanism and the electronic and magnetic properties of these nanoribbons were comprehensively studied by means of a multitechnique approach. Ultra-high vacuum scanning tunneling microscopy showed the occurrence of metal-coordinated nanostructures at room temperature and their evolution into nanoribbons through formal [2+2] cycloaddition at 475 K. Frequency-shift non-contact atomic force microscopy images clearly proved the presence of bridging cyclobutadiene moieties upon covalent coupling of activated tetracene molecules. Insight into the electronic and vibrational properties of the so-formed ribbons was obtained by scanning tunneling microscopy, Raman spectroscopy, and theoretical calculations. Magnetic properties were addressed from a computational point of view, allowing us to propose promising candidates to magnetic acene-based ribbons incorporating four-membered rings. The reported findings will increase the understanding and availability of new graphene-based nanoribbons with high potential in future spintronics.