Furanosyl Oxocarbenium Ion Conformational Energy Landscape Maps as a Tool to Study the Glycosylation Stereoselectivity of 2-Azidofuranoses, 2-Fluorofuranoses and Methyl Furanosyl Uronates

The 3D shape of glycosyl oxocarbenium ions determines their stability and reactivity and the stereochemical course of S_N1 reactions taking place on these reactive intermediates is dictated by the conformation of these species. The nature and configuration of functional groups on the carbohydrate ring affect the stability of glycosyl oxocarbenium ions and control the overall shape of the cations. We herein map the stereoelectronic substituent effects of the C2-azide, C2-fluoride and C4-carboxylic acid ester on the stability and reactivity of the complete suite of diastereoisomeric furanoses by using a combined computational and experimental approach. Surprisingly, all furanosyl donors studied react in a highly stereoselective manner to provide the 1,2-cis products, except for the reactions in the xylose series. The 1,2-cis selectivity for the ribo-, arabino- and lyxo-configured furanosides can be traced back to the lowest-energy ³E or E₃ conformers of the intermediate oxocarbenium ions. The lack of selectivity for the xylosyl donors is related to the occurrence of oxocarbenium ions adopting other conformations.     

Selective Carbanion–Pyridine Coordination of a Reactive P,N Ligand to RhI

Ligands with reactive carbon sites in the periphery of a metal center have emerged as a powerful approach for metal–ligand bond activation. These reactive carbon sites are commonly generated by deprotonation strategies. Carbon–silicon bond cleavage is a potential alternative to access such constructs. Herein, the monodesilylation of bis-silyl-substituted P,N scaffold PN^Si2 in the coordination sphere of [Rh^I(Cl)(CO)( PN^Si2 )] ( 1 ) with sodium azide is disclosed. This affords a unique dinucleating anionic κ²-C,N-κ¹-P ligand with a carbanionic methine carbon atom directly bound to rhodium as part of a four-membered Rh-N-C-C rhodacycle. This dimer undergoes meta-pyridine C−H activation facilitated by weak bases, which leads to a desymmetrization of the system and provides a σ,π-bridging 3-pyridyl fragment bound to Rh^I. The facile Si−C cleavage strategy may pave the way to studying the reactivity and functionalization of a variety of κ²-C,N-coordinated pyridine scaffolds for selective transformations.     

Integrated Molecular Logic Using a Multistate Electrochromic Platform

Herein, we present an approach that integrates molecular logic functions using surface-confined metallo-organic assemblies. These assemblies are electrochromic and mimic the behaviour of logic elements. The logic elements are addressed individually by electrochemical methods, and their outputs are simultaneously read-out optically by UV/Vis absorption spectroscopy. The versatility of our setup is demonstrated by the integration of two multi-component assemblies; each acting as ternary logic elements. We used also a laminated cell configuration to demonstrate color-to-color and color-to-transparent transitions. This concept offers a route for the future development of devices with multiple logic states.     

A method of constructing 2-resolvable t-designs for $$t=3,4$$ t = 3 , 4

Designs, Codes and Cryptography - The paper introduces a method for constructing 2-resolvable t-designs for $$t=3,4$$ . The main idea is based on the assumption that there exists a partition of a...     

New fused pyrroles with rA1/A2A antagonistic activity as potential therapeutics for neurodegenerative disorders

Molecular Diversity - In a pilot study, eleven pyrrolopyridine and pyrrolopyrimidine derivatives (specifically, 7-azaindole and 7-deazapurine derivatives) were synthesised by Suzuki cross-coupling...     

Highly sensitive and rapid determination of tacrolimus in peripheral blood mononuclear cells by liquid chromatography–tandem mass spectrometry

After solid organ transplantation, tacrolimus is given to prevent rejection. Therapeutic drug monitoring is used to reach target concentrations of tacrolimus in whole blood. Because the site of action of tacrolimus is the lymphocyte, and tacrolimus binds ~80% to erythrocytes, the intracellular tacrolimus concentration in lymphocytes is possibly more relevant. For this purpose, we aimed to develop, improve and validate a UPLC–MS/MS method to measure tacrolimus concentrations in isolated peripheral blood mononuclear cells (PBMCs). PBMCs were isolated using a Ficoll separation technique, followed by a washing step using red blood cell lysis. A cell suspension of 50 μL containing 1 million PBMCs was used in combination with MagSiMUS‐TDM^PREP. To each sample we added 30 μL lysis buffer, 20 μL reconstitution buffer containing ¹³C²H₄‐tacrolimus as internal standard, 40 μL MagSiMUS‐TDM^PREP Type I Particle Mix and 175 μL Organic Precipitation Reagent VI for methanol‐based protein precipitation. A 10 μL aliquot of the supernatant was injected into the UPLC–MS/MS system. The method was validated, resulting in high sensitivity and specificity. The method was linear (r² = 0.997) over the range 5.0–1250 pg/1 × 10⁶ PBMCs. The inaccuracy was <5% and the imprecision was <15%. The washing steps following Ficoll isolation could be performed at either room temperature or on ice, with no effect of the temperature on the results. A method for the analysis of tacrolimus concentrations in PBMCs was developed and successfully validated. Further research will be performed to investigate the correlation between concentrations in PBMCs and clinical outcome.     

On the nature of ion-stabilized cytosine pairs in DNA i-motifs: The importance of charge transfer processes

Recent experimental results indicate that the stability of non-Watson-Crick DNA i-motif structures can be influenced by the presence of various metal cations. Whereas Au⁺, Cu⁺, and Ag⁺ are stabilizing agents, alkali metal ions like Na⁺ or Li⁺ are known to destabilize the i-motif. In terms of reduced ion-cytosine complexes, we rationalize the experimental observations with the help of standard and conceptual density functional theory (DFT) calculations. Our results highlight the importance of coordinating electrostatic bonds with partially covalent character for the stability of the ion-cytosine complex. The occurrence of these bonds can be mainly attributed to charge transfer processes between two cytosines and the transition metal ions, which can be either explained by frontier molecular orbital theory in combination with a bond critical point analysis, or by the concept of chemical reactivity indices within a conceptual DFT approach. The results of our calculations establish a consistent theoretical framework to understand the experimentally observed behavior, and are also important in order to achieve more detailed insights into nucleobase pairing mechanisms in general.     

Synthesis,Crystal Structure,and Selected Properties of [Au(S2CNH2)2]SCN: A Precursor for Gold Macro-Needles Consisting of Gold Nanoparticles Glued by Graphitic Carbon Nitride

A new preparation route is developed for the synthesis of needle-like crystals of [Au(S₂CNH₂)₂]SCN, which avoids disproportionation of the Au^I salt used as a starting material. In the crystal structure, the two crystallographically independent Au^III centers are in a square-planar environment of two S₂CNH₂ ligands. The Hirshfeld surface analysis reveals the presence of noncovalent intermolecular S⋅⋅⋅S interactions, which are essential for the spatial arrangement of the molecules. Density functional theory (DFT) calculations including dispersion and damping corrections result in a unit cell volume very close to the value determined experimentally. Thermal decomposition in an inert atmosphere generates black needles with lengths of up to 500 μm. X-ray powder diffraction and pair distribution function analyses demonstrate that the needles are composed of nanosized crystals with a volume-weighted average domain size of 20(1) nm. According to results of X-ray photoemission experiments, the black needles are covered by a nitrogen-rich carbon nitride with composition near (CN)₂N. ¹³C solid-state NMR investigations indicate that two different carbon species are present, with signals corresponding well to heptazine units as in melon and triazine units as in poly(triazin imide) type compounds. Scanning transmission electron microscopy tomography evidences that the needles are composed of slightly elongated nanoparticles.     

Effective Power Series Computations

Foundations of Computational Mathematics - Let K be an effective field of characteristic zero. An effective tribe is a subset of $$K [[z_1, z_2, \ldots ]] = K \cup K {[}[z_1]] \cup K [[z_1, z_2]]...