Monitoring electrophilic intermediates in reactions of thiols in aqueous solution directly with F NMR.

Mechanistic studies of thiol reactivity can be challenging because electrophilic reaction intermediates, such as sulfenic acids (RSOH) and sulfenyl chlorides (RSCl), are generally too reactive to be observed directly. Herein we report the design and synthesis of a sterically-encumbered fluorinated triptycene thiol which enables direct observation of reaction intermediates in aqueous buffer by F NMR, as demonstrated in reactions with hydrogen peroxide and hypochlorous acid. Reactions with HO resulted in the formation of a persistent RSOH species, which was subsequently converted to a sulfinic acid (RSOH) and then a sulfonic acid (RSOH), while RSCl was found to be the intermediate in reactions with HOCl.

The photoactivated dynamics of dGpdC and dCpdG sequences in DNA: a comprehensive quantum mechanical study.

Study of alternating DNA GC sequences by different time-resolved spectroscopies has provided fundamental information on the interaction between UV light and DNA, a process of great biological importance. Multiple decay paths have been identified, but their interplay is still poorly understood. Here, we characterize the photophysics of GC-DNA by integrating different computational approaches, to study molecular models including up to 6 bases described at a full quantum mechanical level.

A redox-enabled strategy for intramolecular hydroamination.

Metal- or acid-catalyzed intramolecular hydroamination and Cope-type intramolecular hydroamination, a distinct concerted approach using hydroxylamines, typically suffer from significant synthetic limitations. Herein we report a process for intramolecular hydroamination that uses a redox-enabled strategy relying on efficient generation of hydroxylamines by oxidation, followed by Cope-type hydroamination, then reduction of the resulting pyrrolidine -oxide. The steps are performed sequentially in a single pot, no catalyst is required, the conditions are mild, the process is highly functional group tolerant, and no chromatography is generally required for isolation.

Generation of bright monomeric red fluorescent proteins computational design of enhanced chromophore packing.

Red fluorescent proteins (RFPs) have found widespread application in chemical and biological research due to their longer emission wavelengths. Here, we use computational protein design to increase the quantum yield and thereby brightness of a dim monomeric RFP (mRojoA, quantum yield = 0.02) by optimizing chromophore packing with aliphatic residues, which we hypothesized would reduce torsional motions causing non-radiative decay.

Temperature-dependence of radical-trapping activity of phenoxazine, phenothiazine and their aza-analogues clarifies the way forward for new antioxidant design.

The prediction and/or rationalization of diarylamine radical-trapping antioxidant (RTA) activity at the elevated temperatures where they are most useful presents a significant challenge, precluding the development of new technology. Whilst structure-activity relationships at ambient temperatures are well established, their predictive capacity at elevated temperatures is poor due to competing reactions. A striking example involves phenoxazine, which is a superior RTA relative to its sulfur analog phenothiazine at ambient temperature ( = 3.

Reactivity of -acyl hydrazone probes with the mammalian proteome.

Small molecule probes with distinct reactivities are useful tools for the identification and characterization of protein modifications and function. Herein, we show that hydrazone probes with an -carbamate structural motif react differently from -carbamates within the human proteome. Mass spectrometry analysis of probe-treated mammalian cell lysates identified several proteins that were covalently modified by the hydrazone probes, including the cytidine deaminase APOBEC3A.

Mechanochemical Preparations of Anion Coordinated Architectures Based on 3-Iodoethynylpyridine and 3-Iodoethynylbenzoic Acid.

10.1002/open.201900194.

Biocompatibility and photo-induced antibacterial activity of lignin-stabilized noble metal nanoparticles.

One-pot thermal and photochemical syntheses of lignin-doped silver and gold nanoparticles were developed and their antimicrobial properties were studied against and . The nature of the lignin as well as the metal are directly involved in the antimicrobial activity observed in these nanocomposites. Whereas one of the nanocomposites is innocuous under dark conditions and shows photoinduced activity only against , the rest of the lignin-coated silver nanoparticles studied show antimicrobial activity under dark and light conditions for both bacteria strains.

Is Single-Molecule Fluorescence Spectroscopy Ready To Join the Organic Chemistry Toolkit? A Test Case Involving Click Chemistry.

Single molecule spectroscopy (SMS) has matured to a point where it can be used as a convenient tool to guide organic synthesis and drug discovery, particularly applicable to catalytic systems where questions related to homogeneous vs heterogeneous pathways are important. SMS can look at intimate mechanistic details that can inspire major improvements of the catalyst performance, its recovery, and reuse. Here, we use the click reaction between alkynes and azides as an example where improvements at the bench have been inspired and validated using single-molecule fluorescence spectroscopy.

Conformational Dynamics of DNA G-Quadruplex in Solution Studied by Kinetic Capillary Electrophoresis Coupled On-line with Mass Spectrometry.

G-quadruplex-forming DNA/RNA sequences play an important role in the regulation of biological functions and development of new anticancer and anti-aging drugs. In this work, we couple on-line kinetic capillary electrophoresis with mass spectrometry (KCE-MS) to study conformational dynamics of DNA G-quadruplexes in solution. We show that peaks shift and its widening in KCE can be used for measuring rate and equilibrium constants for DNA-metal affinity interactions and G-quadruplex formation; and ion mobility mass spectrometry (IM-MS) provides information about relative sizes, absolute molecular masses and stoichiometry of DNA complexes.

Conformational Dynamics of DNA G-Quadruplex in Solution Studied by Kinetic Capillary Electrophoresis Coupled On-line with Mass Spectrometry.

Invited for this months cover is the group of Prof. Maxim V. Berezovski.

Mechanistic analysis of azine N-oxide direct arylation: evidence for a critical role of acetate in the Pd(OAc)2 precatalyst.

Detailed mechanistic studies on the palladium-catalyzed direct arylation of pyridine N-oxides are presented. The order of each reaction component is determined to provide a general mechanistic picture. The C-H bond cleaving step is examined in further detail through computational studies, and the calculated results are in support of an inner-sphere concerted metalation-deprotonation (CMD) pathway.

The Synthesis of a Novel Strained Diyneparacyclophane and Its Dimer by Metal-Mediated Coupling.

Relieve strain with a twist! Synthesis of the paracyclophane 1 and its dimer 2 employed a sequence of metal-mediated couplings. The X-ray analysis of 2 revealed a helical twist inherent in this structure, which created extended arms, that trapped a molecule of solvent. A carboxylic acid derivative of 1 was also prepared, and its structure indicated the diyne rod moiety of 1 is distorted more than in analogous compounds.