Two new structurally related strontium gallium nitrides: Sr4GaN3O and Sr4GaN3(CN2)

The strontium gallium oxynitride Sr(4)GaN(3)O and nitride-carbodiimide Sr(4)GaN(3)(CN(2)) are reported, synthesized as single crystals from molten sodium at 900 degrees C. Red Sr(4)GaN(3)O crystallizes in space group Pbca (No. 61) with a = 7.4002(1) Angstroms, b = 24.3378(5) Angstroms, c = 7.4038(1) Angstroms, and Z = 8, as determined from single-crystal X-ray diffraction measurements at 150 K. The structure may be viewed as consisting of slabs [Sr(4)GaN(3)](2+) containing double layers of isolated [GaN(3)](6-) triangular anions arranged in a "herringbone" fashion, and these slabs are separated by O(2-) anions. Brown Sr(4)GaN(3)(CN(2)) has a closely related structure in which the oxide anions in the Sr(4)GaN(3)O structure are replaced by almost linear carbodiimide [CN(2)](2-) anions [Sr(4)GaN(3)(CN(2)): space group P2(1)/c (No. 14), a = 13.4778(2) Angstroms, b = 7.4140(1) Angstroms, c = 7.4440(1) Angstroms, beta = 98.233(1) degrees, and Z = 4].     

Controlled microfluidic encapsulation of cells, proteins, and microbeads in lipid vesicles

Cells have been encapsulated inside lipid vesicles by using a new microfluidic lipid vesicle formulation technique. Lipid vesicles are formulated within minutes without using toxic lipid solvents. The encapsulation efficiency inside the vesicles is controlled by the microfluidic flows. Green fluorescent proteins (GFP), carcinoma cells, and bead encapsulated vesicles have mean diameters of 27.2 mum, 62.4 mum, and 55.9 mum, respectively. The variations of vesicle sizes are approximately 20% for the GFP and cell encapsulated vesicles and approximately 10% for the bead encapsulated vesicles.     

Sobolev estimates for the Cauchy–Riemann complex on <Emphasis Type="Italic">C</Emphasis><Superscript>1</Superscript> pseudoconvex domains

Let be a bounded pseudoconvex domain with C ^k boundary, k ≥ 1. In this paper, we will prove that the Cauchy–Riemann operator has a bounded solution operator in the Sobolev space for all .     

Metastable doubly threaded [3]rotaxanes with a large macrocycle

Ring size is a critically important parameter in many interlocked molecules as it directly impacts many of the unique molecular motions that they exhibit. Reported herein are studies using one of the largest macrocycles reported to date to synthesize doubly threaded [3]rotaxanes. A large ditopic 46 atom macrocycle containing two 2,6-bis(N-alkyl-benzimidazolyl)pyridine ligands has been used to synthesize several metastable doubly threaded [3]rotaxanes in high yield (65–75% isolated) via metal templating. Macrocycle and linear thread components were synthesized and self-assembled upon addition of iron(ii) ions to form the doubly threaded pseudo[3]rotaxanes that could be subsequently stoppered using azide–alkyne cycloaddition chemistry. Following demetallation with base, these doubly threaded [3]rotaxanes were fully characterized utilizing a variety of NMR spectroscopy, mass spectrometry, size-exclusion chromatography, and all-atom simulation techniques. Critical to the success of accessing a metastable [3]rotaxane with such a large macrocycle was the nature of the stopper group employed. By varying the size of the stopper group it was possible to access metastable [3]rotaxanes with stabilities in deuterated chloroform ranging from a half-life of <1 minute to ca. 6 months at room temperature potentially opening the door to interlocked materials with controllable degradation rates.

Multiple metastable doubly threaded [3]rotaxanes using a large 46 atom ring were prepared and fully characterized. Varying the stopper group size gave a range of interlocked stabilities in CDCl₃ from a half-life of <1 minute to ca. 6 months.     

In Vivo Evaluation of (−)-Zampanolide Demonstrates Potent and Persistent Antitumor Efficacy When Targeted to the Tumor Site

Microtubule-stabilizing agents (MSAs) are a class of compounds used in the treatment of triple-negative breast cancer (TNBC), a subtype of breast cancer where chemotherapy remains the standard-of-care for patients. Taxanes like paclitaxel and docetaxel have demonstrated efficacy against TNBC in the clinic, however new classes of MSAs need to be identified due to the rise of taxane resistance in patients. (−)-Zampanolide is a covalent microtubule stabilizer that can circumvent taxane resistance in vitro but has not been evaluated for in vivo antitumor efficacy. Here, we determine that (−)-zampanolide has similar potency and efficacy to paclitaxel in TNBC cell lines, but is significantly more persistent due to its covalent binding. We also provide the first reported in vivo antitumor evaluation of (−)-zampanolide where we determine that it has potent and persistent antitumor efficacy when delivered intratumorally. Future work on zampanolide to further evaluate its pharmacophore and determine ways to improve its systemic therapeutic window would make this compound a potential candidate for clinical development through its ability to circumvent taxane-resistance mechanisms.     

ChemInform Abstract: Towards Detection of a Long‐Lived Protonated Metal Cation: Generation of GeH2+ Using High‐Energy Collisions.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.     

Vinyl Halide-Modified Unsaturated Cyclitols are Mechanism-Based Glycosidase Inhibitors

Suitably configured allyl ethers of unsaturated cyclitols act as substrates of β-glycosidases, reacting via allylic cation transition states. Incorporation of halogens at the vinylic position of these carbasugars, along with an activated leaving group, generates potent inactivators of β-glycosidases. Enzymatic turnover of these halogenated cyclitols (F, Cl, Br) displayed a counter-intuitive trend wherein the most electronegative substituents yielded the most labile pseudo-glycosidic linkages. Structures of complexes with the Sulfolobus β-glucosidase revealed similar enzyme-ligand interactions to those seen in complexes with a 2-fluorosugar inhibitor, the lone exception being displacement of tyrosine 322 from the active site by the halogen. Mutation of Y322 to Y322F largely abolished glycosidase activity, consistent with lost interactions at O5, but minimally affected (7-fold) rates of carbasugar hydrolysis, yielding a more selective enzyme for unsaturated cyclitol ether hydrolysis.     

Enzymatic Benzofuranoindoline Formation in the Biosynthesis of the Strained Bridgehead Bicyclic Dipeptide (+)-Azonazine A

We uncovered and reconstituted a concise biosynthetic pathway of the strained dipeptide (+)-azonazine A from marine-derived Aspergillus insulicola. Formation of the hexacyclic benzofuranoindoline ring system from cyclo-(l -Trp-N-methyl-l -Tyr) is catalyzed by a P450 enzyme through an oxidative cyclization. Supplementing the producing strain with various indole-substituted tryptophan derivatives resulted in the generation of a series of azonazine A analogs.