In Situ Generated Gold Nanoparticles on Active Carbon as Reusable Highly Efficient Catalysts for a C −C Stille Coupling

Gold nanoparticle catalysts are important in many industrial production processes. Nevertheless, for traditional C ?C cross‐coupling reactions they have been rarely used and Pd catalysts usually give a superior performance. Herein we report that in situ formed gold metal nanoparticles are highly active catalysts for the cross coupling of allylstannanes and activated alkylbromides to form C ?C bonds. Turnover numbers up to 29 000 could be achieved in the presence of active carbon as solid support, which allowed for convenient catalyst recovery and reuse. The present study is a rare case where a gold metal catalyst is superior to Pd catalysts in a cross‐coupling reaction of an organic halide and an organometallic reagent.     

What is the role of acid–acid interactions in asymmetric phosphoric acid organocatalysis? A detailed mechanistic study using interlocked and non-interlocked catalysts

Organocatalysis has revolutionized asymmetric synthesis. However, the supramolecular interactions of organocatalysts in solution are often neglected, although the formation of catalyst aggregates can have a strong impact on the catalytic reaction. For phosphoric acid based organocatalysts, we have now established that catalyst–catalyst interactions can be suppressed by using macrocyclic catalysts, which react predominantly in a monomeric fashion, while they can be favored by integration into a bifunctional catenane, which reacts mainly as phosphoric acid dimers. For acyclic phosphoric acids, we found a strongly concentration dependent behavior, involving both monomeric and dimeric catalytic pathways. Based on a detailed experimental analysis, DFT-calculations and direct NMR-based observation of the catalyst aggregates, we could demonstrate that intermolecular acid–acid interactions have a drastic influence on the reaction rate and stereoselectivity of asymmetric transfer-hydrogenation catalyzed by chiral phosphoric acids.

Supramolecular acid–acid interactions lead to competing monomeric and dimeric pathways in phosphoric acid catalysis – so that stereoselectivities depend on catalyst concentration.     

Comparison of monomethoxy‐, dimethoxy‐, and trimethoxysilane anchor groups for surface‐initiated RAFT polymerization from silica surfaces

The immobilization of reversible addition–fragmentation chain transfer (RAFT) agents on silica for surface‐initiated RAFT polymerizations (SI‐RAFT) via the Z‐group approach was studied systematically in dependence of the functionality of the RAFT‐agent anchor group. Monoalkoxy‐, dialkoxy‐, and trialkoxy silyl ether groups were incorporated into trithiocarbonate‐type RAFT agents and bound to planar silica surfaces as well as to silica nanoparticles. The immobilization efficiency and the structure of the bound RAFT‐agent film varied strongly in dependence of the used solvent (toluene vs. 1,2‐dimethoxyethane) and the anchor group functionality, as evidenced by atomic force microscopy, transmission electron microscopy, dynamic light scattering, and UV/Vis spectroscopy. Surface‐initiated RAFT polymerizations using functionalized silica nanoparticles revealed that grafted oligomers, which often occur in SI‐RAFT, are not formed within the crosslinked structures that originate from the immobilization, and that RAFT‐agent films that show less aggregation during the immobilization are more efficient during SI‐RAFT in terms of polymer grafting density. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 103–113     

1,2,4,5-Tetrakis(tetramethylguanidino)-3,6-diethynyl-benzenes: Fluorescent Probes,Redox-Active Ligands and Strong Organic Electron Donors

In this work, the change of reactivity induced by the introduction of two para-ethynyl substituents (CCSi(iPr)₃ or CCH) to the organic electron-donor 1,2,4,5-tetrakis(tetramethylguanidino)-benzene is evaluated. The redox-properties and redox-state dependent fluorescence are evaluated, and dinuclear Cu^I and Cu^II complexes synthesized. The Lewis-acidic B(C₆F₅)₃ substitutes the proton of the ethynyl −CCH groups to give new anionic −CCB(C₆F₅)₃⁻ substituents, leading eventually to a novel dianionic strong electron donor in its diprotonated form. Its two-electron oxidation with dioxygen in the presence of a copper catalyst yields the first redox-active guanidine that is neutral (instead of cationic) in its oxidized form.     

Divergent Synthesis of Bioactive Dithiodiketopiperazine Natural Products Based on a Double C(sp3)−H Activation Strategy

This article provides a detailed report of our efforts to synthesize the dithiodiketopiperazine (DTP) natural products (−)-epicoccin G and (−)-rostratin A using a double C(sp³)−H activation strategy. The strategy's viability was first established on a model system lacking the C8/C8’ alcohols. Then, an efficient stereoselective route including an organocatalytic epoxidation was secured to access a key bis-triflate substrate. This bis-triflate served as the functional handles for the key transformation of the synthesis: a double C(sp³)−H activation. The successful double activation opened access to a common intermediate for both natural products in high overall yield and on a multigram scale. After several unsuccessful attempts, this intermediate was efficiently converted to (−)-epicoccin G and to the more challenging (−)-rostratin A via suitable oxidation/reduction and protecting group sequences, and via a final sulfuration that occurred in good yield and high diastereoselectivity. These efforts culminated in the synthesis of (−)-epicoccin G and (−)-rostratin A in high overall yields (19.6 % over 14 steps and 12.7 % over 17 steps, respectively), with the latter being obtained on a 500 mg scale. Toxicity assessments of these natural products and several analogues (including the newly synthesized epicoccin K) in the leukemia cell line K562 confirmed the importance of the disulfide bridge for activity and identified dianhydrorostratin A as a 20x more potent analogue.     

Determination of a novel antifibrotic small molecule GDC‐3280 in human plasma and urine by liquid chromatography tandem mass spectrometry to support its first‐in‐human clinical trial

A specific and robust LC–MS/MS method was developed and validated for the quantitative determination of GDC‐3280 in human plasma and urine. The nonspecific binding associated with urine samples was overcome by the addition of CHAPS. The sample volume was 25 μL for either matrix, and supported liquid extraction was employed for analyte extraction. d6‐GDC‐3280 was used as the internal standard. Linear standard curves (R² > 0.9956) were established from 5.00 to 5000 ng/mL in both matrices with quantitation extended to 50,000 ng/mL through dilution. In plasma matrix, the precision (RSD) ranged from 1.5 to 9.9% (intra‐run) and from 2.4 to 7.2% (inter‐run); the accuracy (RE) ranged from 96.1 to 107% (intra‐run) and from 96.7 to 104% (inter‐run). Similarly, in urine the precision was 1.5–6.2% (intra‐run) and 1.9–6.1% (inter‐run); the accuracy was 83.1–99.3% (intra‐run) and 87.1–98.3% (inter‐run). Good recovery (>94%) and negligible matrix effect were achieved in both matrices. Long‐term matrix stability was established for at least 703 days in plasma and 477 days in urine. Bench‐top stability of 25 h and five freeze–thaw cycles were also confirmed in both matrices. The method was successfully implemented in GDC‐3280's first‐in‐human trial for assessing its pharmacokinetic profiles.     

Synthesis of α-fluoro-α,β-unsaturated esters monitored by 1D and 2D benchtop NMR spectroscopy

For optimization and control of pharmaceutically and industrially important reactions, chemical information is required in real time. Instrument size, handling, and operation costs are important criteria to be considered when choosing a suitable analytical method apart from sensitivity and resolution. This present study explores the use of a robust and compact nuclear magnetic resonance (NMR) spectrometer to monitor the stereo-selective formation of α-fluoro-α,β-unsaturated esters from α-fluoro-β-keto esters via deprotonation and deacylation in real time. These compounds are precursors of various pharmaceutically active substances. The real-time study revealed the deprotonation and deacylation steps of the reaction. The reaction was studied at temperatures ranging from 293 to 333 K by interleaved one-dimensional ¹H and ¹⁹F and two-dimensional ¹H–¹H COSY experiments. The kinetic rate constants were evaluated using a pseudo first-order kinetic model. The activation energies for the deprotonation and deacylation steps were determined to 28 ± 2 and 63.5 ± 8 kJ/mol, respectively. This showed that the deprotonation step is fast compared with the deacylation step and that the deacylation step determines the rate of the overall reaction. The reaction was repeated three times at 293 K to monitor the repeatability and stability of the system. The compact NMR spectrometer provided detailed information on the mechanism and kinetics of the reaction, which is essential for optimizing the synthetic routes for stepwise syntheses of pharmaceutically active substances.     

Anion‐Mediated Effects on the Size and Mechanical Properties of Enzymatically Crosslinked Suckerin Hydrogels

The suckerin family of proteins, identified from the squid sucker ring teeth assembly, offers unique mechanical properties and potential advantages over other natural biomaterials. In this study, a small suckerin isoform, suckerin‐12, is used to create enzymatically crosslinked, macro‐scale hydrogels. Upon exposure to specific salt conditions, suckerin‐12 hydrogels contracted into a condensed state where mechanical properties are found to be modulated by the salt anion present. The rate of contraction is found to correlate well with the kosmotropic arm of the Hofmeister anion series. However, the observed changes in hydrogel mechanical properties are better explained by the ability of the salt to neutralize charges in suckerin‐12 by deprotonization or charge screening. Thus, by altering the anions in the condensing salt solution, it is possible to tune the mechanical properties of suckerin‐12 hydrogels. The potential for suckerins to add new properties to materials based on naturally‐derived proteins is highlighted.     

Bi-Sobolev solutions to the prescribed Jacobian inequality in the plane with Lp data and applications to nonlinear elasticity

We construct planar bi-Sobolev mappings whose local volume distortion is bounded from below by a given function $f\in L^p$ with $p>1$. More precisely, for any $1<q<(p+1)/2$ we construct $W^{1,q}$-bi-Sobolev maps with identity boundary conditions; for $f\in L^{\infty }$, we provide bi-Lipschitz maps. The basic building block of our construction are bi-Lipschitz maps which stretch a given compact subset of the unit square by a given factor while preserving the boundary. The construction of these stretching maps relies on a slight strengthening of the celebrated covering result of Alberti, Csörnyei, and Preiss for measurable planar sets in the case of compact sets. We apply our result to a model functional in nonlinear elasticity, the integrand of which features fast blowup as the Jacobian determinant of the deformation becomes small. For such functionals, the derivation of the equilibrium equations for minimizers requires an additional regularization of test functions, which our maps provide.     

Bridging the Green Gap: Metal–Organic Framework Heteromultilayers Assembled from Porphyrinic Linkers Identified by Using Computational Screening

In organic photovoltaics, porphyrins (PPs) are among the most promising compounds owing to their large absorption cross-section, wide spectral range, and stability. Nevertheless, a precise adjustment of absorption band positions to reach a full coverage of the so-called green gap has not been achieved yet. We demonstrate that a tuning of the PP Q- and Soret bands can be carried out by using a computational approach for which substitution patterns are optimized in silico. The most promising candidate structures were then synthesized. The experimental UV/Vis data for the solvated compounds were in excellent agreement with the theoretical predictions. By attaching further functionalities, which allow the use of PP chromophores as linkers for the assembly of metal-organic frameworks (MOFs), we were able to exploit packing effects resulting in pronounced redshifts, which allowed further optimization of the photophysical properties of PP assemblies. Finally, we use a layer-by-layer method to assemble the PP linkers into surface-mounted MOFs (SURMOFs), thus obtaining high optical quality, homogeneous and crystalline multilayer films. Experimental results are in full accord with the calculations, demonstrating the huge potential of computational screening methods in tailoring MOF and SURMOF photophysical properties.