Mass spectrometric stereoisomeric differentiation between α- and β-ascorbic acid 2-O-glucosides. Experimental and density functional theory study

L-Ascorbic acid and two distinct anomers, namely the α-D-glucopyranosyl and β-D-glucopyranosyl-(1→2)-L-ascorbic acid (stereoisomers), were studied within the scope of collision-induced dissociation (CID) experiments, performed by linear ion acceleration and collision with argon atoms inside a hexapole quadrupole hexapole ion beam guide, which is coupled to an ion cyclotron resonance (ICR) cell with a 12 Tesla magnet for high-resolution measurements. Loss of C(2)H(4)O(2) neutral from the [M-H](-) anion of L-ascorbic acid was observed. Density functional theory (DFT) calculations on the 6-311+G(2d,p)//6-31+G(d) level of theory reveal a new concerted mechanism for an intramolecular gas-phase rearrangement, through which the observed ejected neutral C(2)H(4)O(2) can take place. A similar rearrangement also occurs in the case of α- and β-D-glucopyranosyl-(1→2)-L-ascorbic acid. For the α isomer, only homolytic glycoside fragmentation was observed. For the β isomer, both homolytic and heterolytic glycoside cleavages were possible. The mechanisms behind all observed fragmentation pathways were fully understood by the implementation of accurate DFT calculations. Stereoisomeric differentiation between α and β isomers of the L-ascorbic acid-2-O-glucoside could be revealed by tandem mass spectrometry (MS/MS) experiments and were explained theoretically.     

Synthesis of silver/poly(2-hydroxyethyl methacrylate) particles via a combination of inverse miniemulsion and silver ion reduction in a "nanoreactor"

Silver salt/poly(2-hydroxyethyl methacrylate) (poly(HEMA)) hybrid particles were first prepared by inverse miniemulsion polymerization of 2-hydroxyethyl methacrylate (HEMA) with silver tetrafluoroborate (AgBF(4)) as a lipophobe. High silver salt loads of up to 13% with respect to the disperse phase were achieved. The silver/poly(HEMA) hybrid particles were subsequently formed via a gas-phase in situ reduction of AgBF(4) by hydrazine on the surfaces of silver salt/poly(HEMA) particles. The formation of silver nanoparticles was confirmed by UV-vis spectroscopy and X-ray diffraction. The morphology of the hybrid particles of silver salt/poly(HEMA) and silver/poly(HEMA) was fully characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), and dynamic light scattering (DLS). The influence of the reaction parameters including the type and amount of cosolvent, salt content, and type of surfactant on the particle properties and colloidal stability during the reduction process was thoroughly investigated.     

Approach to the Extended States Conjecture

We develop a rather explicit approach concerning the extended states conjecture for the discrete random Schrödinger operator, or more generally for the so-called Anderson-type Hamiltonian. Our work is based on deep mathematical results by Jak?i?–Last (Duke Math. J. 133(1):185–204, 2006). Concretely, we suggest two new directions of research: We provide a formula which may lead the way to a rigorous proof of the conjecture, and an implementation of the proposed approach which yields numerical evidence in favor of the conjecture being true for the discrete random Schrödinger operator in dimension two. Not being based on scaling theory, this method eliminates problems due to boundary conditions, common to previous numerical methods in the field. At the same time, as with any numerical experiment, one cannot exclude finite-size effects with complete certainty. We numerically track the “bulk distribution” (here: the distribution of where we most likely find an electron) of a wave packet initially located at the origin, after iterative application of the discrete random Schrödinger operator.     

A Promiscuous Halogenase for the Derivatization of Flavonoids

Halogenation often improves the bioactive properties of natural products and is used in pharmaceutical research for the generation of new potential drug leads. High regio- and stereospecificity, simple reaction conditions and straightforward downstream processing are the main advantages of halogenation using enzymatic biocatalysts compared to chemical synthetic approaches. The identification of new promiscuous halogenases for the modification of various natural products is of great interest in modern drug discovery. In this paper, we report the identification of a new promiscuous FAD-dependent halogenase, DklH, from Frankia alni ACN14a. The identified halogenase readily modifies various flavonoid compounds, including those with well-studied biological activities. This halogenase has been demonstrated to modify not only flavones and isoflavones, but also flavonols, flavanones and flavanonols. The structural requirements for DklH substrate recognition were determined using a feeding approach. The homology model of DklH and the mechanism of substrate recognition are also proposed in this paper.     

Biomimetic synthesis of the tumor-associated (2,3)-sialyl-T antigen and its incorporation into glycopeptide antigens from the mucins MUC1 and MUC4

Glycoproteins on epithelial tumor cells often exhibit aberrant glycosylation profiles. The incomplete formation of the glycan side chains resulting from a down-regulated glucosamine transfer and a premature sialylation results in additional peptide epitopes, which become accessible to the immune system in mucin-type glycoproteins. These cancer-specific structure alterations are considered to be a promising basis for selective immunological attack on tumor cells. Among the tumor-associated saccharide antigens, the (2,3)-sialyl-T antigen has been identified as the most abundant glycan, found in several different carcinoma cell lines. According to a linear biomimetic strategy, the (2,3)-sialyl-T antigen was synthesized by a stepwise glycan chain extension of a protected galactosamine-threonine precursor. For the construction of immunostimulating antigens combining both peptide and saccharide motifs, this antigen was incorporated into glycopeptide partial structures from the mucins MUC1 and MUC4 by sequential solid-phase synthesis.     

Use of bis-(aminol) ethers derived from N-(S)-(−)-α-methylbenzylamine in reactions with resorcinarenes and double Mannich reactions

The synthesis of some chiral bis-(aminol)ethers are described. Reaction of a solution of the resorcin[4]arene derived from propanal with N,N-bis(methoxymethyl)-N-(S)-(−)-α-methylbenzylamine in toluene at 85 °C initially afforded a 1:1 mixture of two diastereoisomeric tetrakis(benzoxazines). Further, heating of this mixture under reflux in ethanol for 24 h afforded the crystalline (αS),(S)-diastereoisomer in 77% yield. N,N-bis(ethoxymethyl)-N-(S)-(−)-α-methylbenzylamine and N,N-bis(ethoxymethyl)-N-(R)-(+)-α-methylbenzylamine were reacted with β keto esters to afford a 1:1 mixture of the diastereoisomeric double Mannich adducts. Two of the double Mannich adducts were converted into tricyclic ABE analogues of the alkaloid methyllycaconitine 1.     

A [RuRu] Analogue of an [FeFe]‐Hydrogenase Traps the Key Hydride Intermediate of the Catalytic Cycle

The active site of the [FeFe]‐hydrogenases features a binuclear [2Fe]_H sub‐cluster that contains a unique bridging amine moiety close to an exposed iron center. Heterolytic splitting of H₂ results in the formation of a transient terminal hydride at this iron site, which, however is difficult to stabilize. We show that the hydride intermediate forms immediately when [2Fe]_H is replaced with [2Ru]_H analogues through artificial maturation. Outside the protein, the [2Ru]_H analogues form bridging hydrides, which rearrange to terminal hydrides after insertion into the apo‐protein. H/D exchange of the hydride only occurs for [2Ru]_H analogues containing the bridging amine moiety.