A Nickel(II)-Mediated Thiocarbonylation Strategy for Carbon Isotope Labeling of Aliphatic Carboxamides

A series of pharmaceutically relevant small molecules and biopharmaceuticals bearing aliphatic carboxamides have been successfully labeled with carbon-13. Key to the success of this novel carbon isotope labeling technique is the observation that ¹³C-labeled Ni^II-acyl complexes, formed from a ¹³CO insertion step with Ni^II-alkyl intermediates, rapidly react in less than one minute with 2,2’-dipyridyl disulfide to quantitatively form the corresponding 2-pyridyl thioesters. Either the use of ¹³C-SilaCOgen or ¹³C-COgen allows for the stoichiometric addition of isotopically labeled carbon monoxide. Subsequent one-pot acylation of a series of structurally diverse amines provides the desired ¹³C-labeled carboxamides in good yields. A single electron transfer pathway is proposed between the Ni^II-acyl complexes and the disulfide providing a reactive Ni^III-acyl sulfide intermediate, which rapidly undergoes reductive elimination to the desired thioester. By further optimization of the reaction parameters, reaction times down to only 11 min were identified, opening up the possibility of exploring this chemistry for carbon-11 isotope labeling. Finally, this isotope labeling strategy could be adapted to the synthesis of ¹³C-labeled liraglutide and insulin degludec, representing two antidiabetic drugs.     

Color Tuning of Fluorogens for FAST Fluorogen-Activating Protein

Using benzylidene imidazolone core, we created a panel of color-shifted fluorogenic ligands for FAST protein without compromise to the binding efficiency and the utility for live-cell protein labeling. This study highlights the potential of benzylidene imidazolones derivatives for rapid expansion of a pallet of live-cell fluorogenic labeling tools.     

Antimagic orientations of even regular graphs

A labeling of a digraph D with m arcs is a bijection from the set of arcs of D to . A labeling of D is antimagic if no two vertices in D have the same vertex-sum, where the vertex-sum of a vertex for a labeling is the sum of labels of all arcs entering u minus the sum of labels of all arcs leaving u. Motivated by the conjecture of Hartsfield and Ringel from 1990 on antimagic labelings of graphs, Hefetz, Mütze, and Schwartz [On antimagic directed graphs, J. Graph Theory 64 (2010) 219–232] initiated the study of antimagic labelings of digraphs, and conjectured that every connected graph admits an antimagic orientation, where an orientation D of a graph G is antimagic if D has an antimagic labeling. It remained unknown whether every disjoint union of cycles admits an antimagic orientation. In this article, we first answer this question in the positive by proving that every 2-regular graph has an antimagic orientation. We then show that for any integer , every connected, 2d-regular graph has an antimagic orientation. Our technique is new.     

gem-Diethyl Pyrroline Nitroxide Spin Labels: Synthesis,EPR Characterization,Rotamer Libraries and Biocompatibility

The availability of bioresistant spin labels is crucial for the optimization of site-directed spin labeling protocols for EPR structural studies of biomolecules in a cellular context. As labeling can affect proteins’ fold and/or function, having the possibility to choose between different spin labels will increase the probability to produce spin-labeled functional proteins. Here, we report the synthesis and characterization of iodoacetamide- and maleimide-functionalized spin labels based on the gem-diethyl pyrroline structure. The two nitroxide labels are compared to conventional gem-dimethyl analogs by site-directed spin labeling (SDSL) electron paramagnetic resonance (EPR) spectroscopy, using two water soluble proteins: T4 lysozyme and Bid. To foster their use for structural studies, we also present rotamer libraries for these labels, compatible with the MMM software. Finally, we investigate the “true” biocompatibility of the gem-diethyl probes comparing the resistance towards chemical reduction of the NO group in ascorbate solutions and E. coli cytosol at different spin concentrations.     

Using math magic to reinforce algebraic concepts: an exploratory study

An exploratory study was conducted to investigate the use of magic activities in a math course for prospective middle-school math teachers. This research report focuses on a lesson using two versions of math magic: (1) the 5-4-3-2-1-½ Magic involves having students choose a secret number and apply six arithmetic operations in sequence to arrive at a resultant number, and the teacher-magician can spontaneously reveal a student’s secret number from the resultant number; and (2) the Everyone-Got-9 Magic also involves choosing a secret number and applying arithmetic operations in sequence, but everyone will end up with the same resultant number of 9. These magic activities were implemented to reinforce students’ understanding of foundational algebra concepts like variables, expressions, and inverse functions. Analysis of students’ written responses revealed that (1) all students who figured out the trick in the first magic activity did not used algebra, (2) most students could apply what they learned in one trick to a similar trick but not to a different trick, and (3) many students were weak in symbolic representations and manipulations. Responses from a survey and a focus group indicate that students found the magic activities to be fun and intellectually engaging.     

Hyperpolarizing Concentrated Metronidazole 15NO2 Group over Six Chemical Bonds with More than 15 % Polarization and a 20 Minute Lifetime

The NMR hyperpolarization of uniformly ¹⁵N-labeled [¹⁵N₃]metronidazole is demonstrated by using SABRE-SHEATH. In this antibiotic, the ¹⁵NO₂ group is hyperpolarized through spin relays created by ¹⁵N spins in [¹⁵N₃]metronidazole, and the polarization is transferred from parahydrogen-derived hydrides over six chemical bonds. In less than a minute of parahydrogen bubbling at approximately 0.4 μT, a high level of nuclear spin polarization (P_15N) of around 16 % is achieved on all three ¹⁵N sites. This product of ¹⁵N polarization and concentration of ¹⁵N spins is around six-fold better than any previous value determined for ¹⁵N SABRE-derived hyperpolarization. At 1.4 T, the hyperpolarized state persists for tens of minutes (relaxation time, T₁≈10 min). A novel synthesis of uniformly ¹⁵N-enriched metronidazole is reported with a yield of 15 %. This approach can potentially be used for synthesis of a wide variety of in vivo metabolic probes with potential uses ranging from hypoxia sensing to theranostic imaging.     

A Dual-Functional Ferroferric Oxide/Quantum Dots Theranostic Nanoplatform for Fluorescent Labeling and Photothermal Therapy

A biocompatible, nontoxic theranostic nanoplatform consisting of mesoporous silica-coated ferroferric oxide (Fe₃O₄) and Mn-doped ZnS-ZnS quantum dots (QDs) is synthesized via a layer-by-layer method. Transmission electron microscopy, X-ray diffractometer, magnetometry, and fluorophotometer are employed to characterize the nanoplatform. The nanoplatform exhibits excellent superparamagnetic, fluorescent, and light absorption properties. The template method is introduced to form a mesoporous silica structure on the nanoplatform, lowering the mass of the nanoplatform and effectively promoting the absorption efficiency of the incident light compared with the traditional silica layer. In addition, after endocytosis of the nanoplatform, cancer cells are easily detected under a fluorescence microscope because of the excellent fluorescent behavior of QDs. Moreover, in vitro experiments confirm that nanoplatform possesses perfect photothermal effect to destroy tumor cells under laser irradiation. Therefore, ferroferric oxide/QDs nanoplatforms, combined with the functions of fluorescent labeling and photothermal therapy for cancer cells, are expected to be a promising biopotential material in the field of diagnosis and treatment.     

3‐Mercapto‐2,6‐Pyridinedicarboxylic Acid: A Small Lanthanide‐Binding Tag for Protein Studies by NMR Spectroscopy

Paramagnetic effects from lanthanide ions present powerful tools for protein studies by nuclear magnetic resonance (NMR) spectroscopy provided that the lanthanide can be site‐specifically and rigidly attached to the protein. A new, particularly small and rigid lanthanide‐binding tag, 3‐mercapto‐2,6‐pyridinedicarboxylic acid (3MDPA), was synthesized and attached to two different proteins via a disulfide bond. The complexes of the N‐terminal domain of the E. coli arginine repressor (ArgN) with seven different paramagnetic lanthanide ions and Co²⁺ were analyzed in detail by NMR spectroscopy. The magnetic susceptibility anisotropy (Δχ) tensors and metal position were determined from pseudocontact shifts. The 3MDPA tag generated very different Δχ tensor orientations compared to the previously studied 4‐mercaptomethyl‐DPA tag, making it a highly complementary and useful tool for protein NMR studies.     

AlMCM-41介孔分子筛的合成及表征

以拟薄水铝石为铝源、水玻璃为硅源、十六烷基三甲基溴化铵为模板剂,在110℃时水热晶化合成了含Al的MCM-41介孔分子筛.采用X射线衍射(XRD)、N2吸附-脱附、固体29Si、27Al魔角旋转核磁共振技术(MASNMR)、扫描电镜(SEM)及吡啶吸附傅里叶变换红外(FTIR)光谱技术对AlMCM-41分子筛进行了表征.结果表明:AlMCM-41分子筛具有六方排列的孔道结构,同时具有很高的相对结晶度、比表面积和孔容,且孔分布单一;AlMCM-41分子筛中Si原子在骨架内键合的程度更高,使AlMCM-41分子筛具有更好的骨架晶化程度;同时具有四配位骨架铝,使AlMCM-41介孔分子筛具有适当的酸性.