An online nano-LC-ESI-FTICR-MS method for comprehensive characterization of endogenous fragments from amyloid β and amyloid precursor protein in human and cat cerebrospinal fluid

Amyloid precursor protein (APP) is the precursor protein to amyloid β (Aβ), the main constituent of senile plaques in Alzheimer's disease (AD). Endogenous Aβ peptides reflect the APP processing, and greater knowledge of different APP degradation pathways is important to understand the mechanism underlying AD pathology. When one analyzes longer Aβ peptides by low-energy collision-induced dissociation tandem mass spectrometry (MS/MS), mainly long b-fragments are observed, limiting the possibility to determine variations such as amino acid variants or post-translational modifications (PTMs) within the N-terminal half of the peptide. However, by using electron capture dissociation (ECD), we obtained a more comprehensive sequence coverage for several APP/Aβ peptide species, thus enabling a deeper characterization of possible variants and PTMs. Abnormal APP/Aβ processing has also been described in the lysosomal storage disease Niemann-Pick type C and the major large animal used for studying this disease is cat. By ECD MS/MS, a substitution of Asp7 → Glu in cat Aβ was identified. Further, sialylated core 1 like O-glycans at Tyr10, recently discovered in human Aβ (a previously unknown glycosylation type), were identified also in cat cerebrospinal fluid (CSF). It is therefore likely that this unusual type of glycosylation is common for (at least) species belonging to the magnorder Boreoeutheria. We here describe a detailed characterization of endogenous APP/Aβ peptide species in CSF by using an online top-down MS-based method.     

Bounds for Coding Theory over Rings

Coding theory where the alphabet is identified with the elements of a ring or a module has become an important research topic over the last 30 years. It has been well established that, with the generalization of the algebraic structure to rings, there is a need to also generalize the underlying metric beyond the usual Hamming weight used in traditional coding theory over finite fields. This paper introduces a generalization of the weight introduced by Shi, Wu and Krotov, called overweight. Additionally, this weight can be seen as a generalization of the Lee weight on the integers modulo 4 and as a generalization of Krotov’s weight over the integers modulo 2^s for any positive integer s. For this weight, we provide a number of well-known bounds, including a Singleton bound, a Plotkin bound, a sphere-packing bound and a Gilbert–Varshamov bound. In addition to the overweight, we also study a well-known metric on finite rings, namely the homogeneous metric, which also extends the Lee metric over the integers modulo 4 and is thus heavily connected to the overweight. We provide a new bound that has been missing in the literature for homogeneous metric, namely the Johnson bound. To prove this bound, we use an upper estimate on the sum of the distances of all distinct codewords that depends only on the length, the average weight and the maximum weight of a codeword. An effective such bound is not known for the overweight.     

Synthesis of N-Monosubstituted Sulfondiimines by Metal-free Iminations of Sulfilimium Salts

Sulfondiimines are marginalized entities among nitrogen-containing organosulfur compounds, despite offering promising properties for applications in various fields including medicinal and agrochemical. Herein, we present a metal-free and rapid synthetic procedure for the synthesis of N-monosubstituted sulfondiimines that overcomes current limitations in their synthetic accessibility. Particularly, S,S-dialkyl substrates, which are commonly difficult to convert by existing methods, react well with a combination of iodine, 1,8-diazabicyclo[5.4.0]undec-7-en (DBU), and iminoiodinanes (PhINR) in acetonitrile (MeCN) to furnish the corresponding sulfondiimines in yields up to 85 % (25 examples). Valuable “free” NH-N′H-sulfondiimines can then be accessed by N-deprotection under mild reaction conditions. Several experimental observations suggest a mechanistic pathway diverging from the common radical-based iodine/iminoiodinane mechanism. Based on the experimental results in combination with data obtained by ¹H NMR spectroscopy, ESI mass spectrometry, and crystallographic analysis we propose a direct amination from PhINNs and a reaction path via a cationic iodonitrene.     

Polypeptoids by Living Ring‐Opening Polymerization of N‐Substituted N‐Carboxyanhydrides from Solid Supports

The nucleophilic living ring‐opening polymerization of N‐substituted glycine N‐carboxyanhydrides using solid‐phase synthesis resins is reported. By variation of experimental parameters, products with near Poisson distributions are obtained. As opposed to reversible deactivation radical polymerization, the living polymerization is demonstrated to be viable to high monomer conversion and through multiple monomer addition steps. Successful preparation of a multiblock copolypeptoid is proof for a highly living and robust character of the solid‐phase peptoid polymerization.

     

Cyclic and Macrocyclic Molecules Containing Silicon or Tin – Synthesis of Highly Rigid,Potentially Lewis-Acidic Cryptands

Herein we report the syntheses of highly rigid silicon- and tin-containing cyclic and bicyclic compounds with unsaturated organic backbones. The syntheses proceed via di-lithiated diethynylbenzene derivatives. The protocols for the known precursor compounds were significantly improved in a two-step one-pot reaction with yields up to 45 % by alternating addition of the lithiation reagent and starting material. A total of ten compounds were synthesized and the molecular structure in the solid state was elucidated for six novel compounds. Host-guest-experiments with selected molecules were conducted to investigate on the potential of the complexation of small anions. All compounds were characterized by multinuclear NMR spectroscopy and elemental analyses or mass spectrometry and in most parts by SC-XRD analyses.     

The Role of Lewis Acid Sites in γ-Al2O3 Oligomerization

Olefin oligomerization by γ-Al₂O₃ has recently been reported, and it was suggested that Lewis acid sites are catalytic. The goal of this study is to determine the number of active sites per gram of alumina to confirm that Lewis acid sites are indeed catalytic. Addition of an inorganic Sr oxide base resulted in a linear decrease in the propylene oligomerization conversion at loadings up to 0.3 wt %; while, there is a >95 % loss in conversion above 1 wt % Sr. Additionally, there was a linear decrease in the intensity of the Lewis acid peaks of absorbed pyridine in the IR spectra with an increase in Sr loading, which correlates with the loss in propylene conversion, suggesting that Lewis acid sites are catalytic. Characterization of the Sr structure by XAS and STEM indicates that single Sr²⁺ ions are bound to the γ-Al₂O₃ surface and poison one catalytic site per Sr ion. The maximum loading needed to poison all catalytic sites, assuming uniform surface coverage, was ∼0.4 wt % Sr, giving an acid site density of ∼0.2 sites per nm² of γ-Al₂O₃, or approximately 3 % of the alumina surface.     

Density Functional Theory Calculations for Multiple Conformers Explaining the Regio- and Stereoselectivity of Ti-Catalyzed Hydroaminoalkylation Reactions

Hybrid Density Functional Theory (DFT) calculations for multiple conformers of the insertion reactions of a methylenecyclopropane into the Ti−C bond of two differently α-substituted titanaaziridines explain the experimentally observed differences in regioselectivity between catalytic hydroaminoalkylation reactions of methylenecyclopropanes with α-phenyl-substituted secondary amines and corresponding stoichiometric reactions of a methylenecyclopropane with titanaaziridines, which can only be achieved with α-unsubstituted titanaaziridines. In addition, the lack of reactivity of α-phenyl-substituted titanaaziridines as well as the diastereoselectivity of the catalytic and stoichiometric reactions can be understood.