Analytical theory of gamma-encoded double-quantum recoupling sequences in solid-state nuclear magnetic resonance

Many important double-quantum recoupling techniques in solid-state NMR are classified as being gamma-encoded. This means that the phase of the double-quantum effective Hamiltonian, but not its amplitude, depends on the third Euler angle defining the orientation of the molecular spin system in the frame of the magic-angle-spinning rotor. In this paper, we provide closed analytical solutions for the dependence of the powder-average double-quantum-filtered signal on the recoupling times, within the average Hamiltonian approximation for gamma-encoded pulse sequences. The validity of the analytical solutions is tested by numerical simulations. The internuclear distance in a (13)C(2)-labelled retinal is estimated by fitting the analytical curves to experimental double-quantum data.     

On-Surface Formation of Cyano-Vinylene Linked Chains by Knoevenagel Condensation

The rapid development of on-surface synthesis provides a unique approach toward the formation of carbon-based nanostructures with designed properties. Herein, we present the on-surface formation of CN-substituted phenylene vinylene chains on the Au(111) surface, thermally induced by annealing the substrate stepwise at temperatures between 220 °C and 240 °C. The reaction is investigated by scanning tunneling microscopy and density functional theory. Supported by the calculated reaction pathway, we assign the observed chain formation to a Knoevenagel condensation between an aldehyde and a methylene nitrile substituent.     

Development of a Simple and Fast Electrochemical Method for Screening and Stoichiometric Determination of Dimenhydrinate

Dimenhydrinate (DIM) is a salt composed by the combination of two active pharmaceutical ingredients: diphenhydramine (DIP) and 8‐chlorotheophylline (CTP). In this work, the use of batch injection analysis with multiple pulse amperometric detection (BIA‐MPA) was proposed for the first time for fast stoichiometric determination of DIM. DIP (cation) and CTP (anion) were determined simultaneously in pharmaceutical samples with a simple and fast injection procedure (70 injections h^?1). Additional strategies were also proposed for rapid screening of samples containing the DIM salt. By a simple injection of a sample into the BIA system (without using of calibration curve), reliable information about stoichiometry of the DIM salt (1 : 1; DIP:CTP) and presence or absence of interfering species (electroactive) can be achieved.     

Synthesis,Structure, and Reactivity of Diazene Adducts: Isolation of iso‐Diazene Stabilized as a Borane Adduct

This work describes the synthesis and full characterization of a series of GaCl₃ and B(C₆F₅)₃ adducts of diazenes R¹?N?N?R² (R¹=R²=Me₃Si, Ph; R¹=Me₃Si, R²=Ph). Trans‐Ph?N?N?Ph forms a stable adduct with GaCl₃, whereas no adduct, but instead a frustrated Lewis acid–base pair is formed with B(C₆F₅)₃. The cis‐Ph?N?N?Ph ? B(C₆F₅)₃ adduct could only be isolated when UV light was used, which triggers the isomerization from trans‐ to cis‐Ph?N?N?Ph, which provides more space for the bulky borane. Treatment of trans‐Ph?N?N?SiMe₃ with GaCl₃ led to the expected trans‐Ph?N?N?SiMe₃ ? GaCl₃ adduct but the reaction with B(C₆F₅)₃ triggered a 1,2‐Me₃Si shift, which resulted in the formation of a highly labile iso‐diazene, Me₃Si(Ph)N?N; stabilized as a B(C₆F₅)₃ adduct. Trans‐Me₃Si?N?N?SiMe₃ forms a labile cis‐Me₃Si?N?N?SiMe₃ ? B(C₆F₅)₃ adduct, which isomerizes to give the transient iso‐diazene species (Me₃Si)₂N?N ? B(C₆F₅)₃ upon heating. Both iso‐diazene species insert easily into one B?C bond of B(C₆F₅)₃ to afford hydrazinoboranes. All new compounds were fully characterized by means of X‐ray crystallography, vibrational spectroscopy, CHN analysis, and NMR spectroscopy. All compounds were further investigated by DFT and the bonding situation was assessed by natural bond orbital (NBO) analysis.     

Artificial Accelerators of the Molecular Chaperone Hsp90 Facilitate Rate‐Limiting Conformational Transitions

The molecular chaperone Hsp90 undergoes an ATP‐driven cycle of conformational changes in which large structural rearrangements precede ATP hydrolysis. Well‐established small‐molecule inhibitors of Hsp90 compete with ATP‐binding. We wondered whether compounds exist that can accelerate the conformational cycle. In a FRET‐based screen reporting on conformational rearrangements in Hsp90 we identified compounds. We elucidated their mode of action and showed that they can overcome the intrinsic inhibition in Hsp90 which prevents these rearrangements. The mode of action is similar to that of the co‐chaperone Aha1 which accelerates the Hsp90 ATPase. However, while the two identified compounds influence conformational changes, they target different aspects of the structural transitions. Also, the binding site determined by NMR spectroscopy is distinct. This study demonstrates that small molecules are capable of triggering specific rate‐limiting transitions in Hsp90 by mechanisms similar to those in protein cofactors.     

Tapered copolymers of styrene and 4-vinylbenzocyclobutene via carbanionic polymerization for crosslinkable polymer films

Well-defined polystyrene homopolymers with surface-adhesive triethoxysilyl end group were synthesized via living carbanionic polymerization, epoxide end-functionalization and subsequent hydrosilylation with triethoxysilane. Grafting-to performance of polymers with various molecular weight (M_n = 3000–14,000 g mol⁻¹) to a silicon surface was examined in dependence of reaction time, polymer concentration, solvent and number of alkoxysilyl end groups. Crosslinkable polymers for surface modification were synthesized by statistical carbanionic copolymerization of 4-vinylbenzocyclobutene (4-VBCB) and styrene, followed by epoxide end-functionalization and triethoxysilane modification (M_n = 4000–14,000 g mol⁻¹). The copolymers were characterized by ¹H-NMR, THF-SEC, and matrix-assisted laser desorption and ionization time-of-flight mass spectrometry. In situ ¹H-NMR kinetic studies in cyclohexane-d₁₂ provided information regarding the monomer gradient in the polymer chains, with styrene being the more reactive monomer (r_s = 2.75, r_4-VBCB = 0.23). Thin polymer films on silicon wafers were prepared by grafting-to surface modification under conditions derived for the polystyrene homopolymer. The traceless, thermally induced crosslinking reaction of the benzocyclobutene units was studied by DSC in bulk as well as in 3–6 nm thick polymer films. Crosslinked films were analyzed by atomic force microscopy, ellipsometry, and nanoindentation, showing smooth polymer films with an increased modulus. © 2019 The Authors. Journal of Polymer Science published by Wiley Periodicals, Inc. J. Polym. Sci. 2020 , 58, 181–192     

Flow-through amperometric methods for detection of the bioactive compound quercetin: performance of glassy carbon and screen-printed carbon electrodes

Journal of Solid State Electrochemistry - Rapid methods using batch injection analysis (BIA) with amperometric detection were developed for the determination of quercetin extracted from the...     

Real‐Time NMR Spectroscopy for Studying Metabolism

Current metabolomics approaches utilize cellular metabolite extracts, are destructive, and require high cell numbers. We introduce here an approach that enables the monitoring of cellular metabolism at lower cell numbers by observing the consumption/production of different metabolites over several kinetic data points of up to 48 hours. Our approach does not influence cellular viability, as we optimized the cellular matrix in comparison to other materials used in a variety of in‐cell NMR spectroscopy experiments. We are able to monitor real‐time metabolism of primary patient cells, which are extremely sensitive to external stress. Measurements are set up in an interleaved manner with short acquisition times (approximately 7 minutes per sample), which allows the monitoring of up to 15 patient samples simultaneously. Further, we implemented our approach for performing tracer‐based assays. Our approach will be important not only in the metabolomics fields, but also in individualized diagnostics.