4,5-Dicyano-1,2,3-Triazole-A Promising Precursor for a New Family of Energetic Compounds and Its Nitrogen-Rich Derivatives: Synthesis and Crystal Structures.

The nitrogen-rich compounds and intermediates with structure of monocyclic, bicyclic, and fused rings based on 1,2,3-triazole were synthesized and prepared by using a promising precursor named 4,5-dicyano-1,2,3-triazole, which was obtained by the cyclization reaction of diaminomaleonitrile. Their structure and configurational integrity were assessed by Fourier transform-infrared spectroscopy (FT-IR), mass spectrometry (MS), and elemental analysis (EA). Additionally, fourteen compounds were further confirmed by X-ray single crystal diffraction. Meanwhile, the physical properties of four selected compounds (3·H2O, 6·H2O, 10·H2O, and 16) including thermal stability, detonation parameters, and sensitivity were also estimated. All these compounds could be considered to construct more abundant 1,2,3-triazole-based neutral energetic molecules, salts, and complex compounds, which need to continue study in the future in the field of energetic materials.

Synthesis of azobenzenealkylmaleimide probes to photocontrol the enzyme activity of a bacterial histone deacetylase-like amidohydrolase.

A series of azobenzenealkylmaleimides (AMDs) with different spacer length was synthesized and coupled via Michael-Addition to a specific mutant of a bacterial histone deacetylase-like amidohydrolase (HDAH). Michaelis-Menten parameters (Vmax and Km) were employed to characterize the effect of both, the spacer length and the configuration (cis vs. trans) of the attached azobenzene moiety, on the HDAH enzyme activity. The photoswitch behavior of the AMD/enzyme conjugate activity was clearly influenced by the AMD spacer length. This study highlights the importance of steric rearrangement of the photoswitch with respect to the active site and describes a strategy to optimize the photocontrol of HDAH.

Seamless Coupling of Chemical Glycan Release and Labeling for an Accelerated Protein N-Glycan Sample Preparation Workflow.

Analytical methods fr direct quantitative N-glycan analysis require a sequence of sample preparation and clean-up steps that result in reduced glycan recovery. Therefore, we aimed to combine glycan release and labeling steps. Based on the hypothesis that the reaction mechanism for oxidative chemical glycan release comprises a stable glycan isocyanate intermediate, we investigated whether this could be exploited for the in-situ preparation of fluorescent glycan conjugates. ANTS-labeled N-glycans were derived from chicken ovalbumin via an in-situ chemical release/coupling approach and by standard Peptide-N-Glycosidase F (PNGase F) digestion/reductive amination. Synoptic fluorescence-assisted carbohydrate electrophoresis with UV detection (FACE-UV) analysis yielded matching patterns of fluorescent N-glycan bands in the expected electrophoretic mobility range between hexose units GU-5 and GU-11 of the standard. Anthranilamide (2-AB)-glycan conjugates prepared from a test glycoprotein carrying a predominant Core-F glycan gave single predominant peaks in hydrophilic interaction chromatography with fluorescence detection (HILIC-FLD) and electrospray ionization mass spectrometry (ESI-MS) spectra in agreement with sodiated triply charged Core-F-AB conjugates for both the standard and the in-situ coupling methods. The Core-F-AB conjugate prepared by the in-situ coupling approach had a slightly elevated retention time on HILIC-FLD and an ESI-MS m/z peak in line with a urea-bonded glycan-AB conjugate, with closed pyran ring structures on the glycan moiety. Glycan isocyanates intermittently formed during chemical glycan release, which could be utilized to prepare labeled glycan samples directly from glycoproteins and fluorescent dyes bearing a primary amine functional group.

Approaches to α-amino acids via rearrangement to electron-deficient nitrogen: Beckmann and Hofmann rearrangements of appropriate carboxyl-protected substrates.

The titled approaches were effected with various 2-substituted benzoylacetic acid oximes 3 (Beckmann) and 2-substituted malonamic acids 9 (Hofmann), their carboxyl groups being masked as a 2,4,10-trioxaadamantane unit (an orthoacetate). The oxime mesylates have been rearranged with basic Al(2)O(3) in refluxing CHCl(3), and the malonamic acids with phenyliodoso acetate and KOH/MeOH. Both routes are characterized by excellent overall yields. Structure confirmation of final products was conducted with X-ray diffraction in selected cases. The final N-benzoyl and N-(methoxycarbonyl) products are α-amino acids with both carboxyl and amino protection; hence, they are of great interest in peptide synthesis.

Release of protein N-glycans by effectors of a Hofmann carboxamide rearrangement.

Background: Chemical methods for glycan release have gained traction because of their cost efficiency, accelerated reaction time and ability to release glycans not amenable to enzymatic cleavage. Oxidative chemical glycan release via hypochlorite treatment has been shown to be a convenient and efficient method that yields N-glycans similar to classical PNGase F digestion. We observed that the initial steps of the suggested mechanism for the oxidative release of glycans from glycoproteins by hypohalites showed similarities to the initiating steps of the classical Hofmann rearrangement of carboxamides. Therefore, we investigated the ability of different stable effectors of a Hofmann-type carboxamide rearrangement to efficiently and selectively release N-glycans from glycoproteins. Methods: Released glycans obtained from different experimental chemical release approaches were analyzed by HILIC-FLD, BHZ-FACE and ESI-MS and evaluated with respect to electrophoretic mobility, retention time and integrated peak area for resolved glycans. Results: We show that the known Hoffmann catalysts 1,3-dichloro-5,5-dimethylhydantoin, the hypervalent organoiodine (III) compound diacetoxy-iodobenzene as well as in-situ hypobromite generation using Oxone® and potassium bromide are all capable of releasing protein-bound N-glycans in good yield. Among the compounds investigated, diacetoxy-iodobenzene was capable of releasing glycans in the absence of alkali. Detailed investigations of the bromide/Oxone® method revealed a dependence of N-glycan release efficiency from the temporal order of bromide addition to the reaction mix as well as from a molar excess of bromide over Oxone®. Conclusions. These findings suggest that the oxidative release of N-glycans occurs via the initiating steps of a Hofmann carboxamide rearrangement. Hypervalent organoiodine compounds hold the promise of releasing glycans in the absence of alkali. The in-situ generation of hypobromite by bromide/Oxone® produces a consistent defined amount of reagent for rapid N-glycan release for both analytical and preparative purposes.

A Unique Collision-Induced Dissociation Reaction of Cholamine Derivatives of Certain Prostaglandins.

Prostaglandins (PGs) are biologically active metabolites of arachidonic acid containing 20 carbon atoms, a cyclic moiety, and two side chains (A and B) in common. The bioassay of PGs requires high sensitivity because of their low concentration in tissues and blood and has usually been carried out by electrospray ionization tandem mass spectrometry (ESI-MS/MS) in the negative ion mode. Chemical derivatization of PG carboxylic acid groups to introduce positive charge-carrying groups is an established strategy to improve the sensitivity and selectivity of such assays. In this study, we exploited this approach for structural identification of a series of PGs using cholamine derivatization through an amidation reaction. However, we observed that collision-induced dissociation of these derivatives gave rise to unexpected product ions that we postulated were formed by unique long-range intramolecular reactions resulting in dehydration of the B chain accompanied by fragmentation of the A chain through an unusual Hofmann rearrangement. Evidence for the proposed mechanism is presented based on ESI-MS/MS and high resolution mass spectrometry studies of cholamine derivatives of PGE1, PGE2, PGD2, PGI2, and C-17 methyl deuterium-labeled limaprost. Graphical Abstract.