Synthesis of 1-(dimethylsulfamoyl)-2- and 5-imidazolecarboxaldehydes. Rearrangement of 1-(dimethylsulfamoyl)-5-imidazole-carboxaldehyde to the 4-carboxaldehyde

Lithiation of 1-(dimethylsulfamoyl)imidazole by n-butyllithium, followed by substitution with dimethylformamide provided 1-(dimethylsulfamoyl)-2-imidazolecarboxaldehyde in 19% yield. When 1-(dimethylsulfamoyl)-2-(tert-butyldimethylsilyl)imidazole was lithiated by sec-butyllithium, followed by methyl formate, there was obtained 1-(dimethylsulfamoyl)-2-(tert-butyldimethylsilyl)-5-imidazolecarbox-aldehyde (57%). Removal of the silyl group by acetic acid yielded 1-(dimethylsulfamoyl)-5-imidazolecarbxaldehyde ( 11 , 96%) as a gum. Isomerization of 11 took place slowly at room temperature (10 days), or faster in tetrahydrofuran solution containing triethylamine (2 hours) to form crystalline 1-(dimethylsul-famoyl)-4-imidazolecarboxaldehyde (12) in 68% yield. Proton and carbon-13 nmr spectra were analyzed to determine the structure of the isomers. However, only X-ray crystallography established the structure of 1-(dimethylsulfamoyl)-4-imidazolecarboxaldehyde, unequivocally. A mechanism for the isomerization of 11 to 12 is proposed.     

Synthesis and X-ray structure analysis of benzoic acid [1-(6-methyl-2,4-dioxo-3,4-dihydro-2H-pyran-3-yl)eth-(E)-ylidene]-hydrazide with a water molecule (C15H14N2O4?H2O)

The crystal structure of the title compound has been determined by X-ray diffraction methods. It crystallizes in the monoclinic space group P2₁/n with cell parameters a = 7.097(1) Å, b = 19.257(1) Å, c = 10.893(1) Å, = 106.17(2), V = 1429.8(3) ų and Z = 4. The final reliability index is 0.059 for 2419 observed reflections. The molecule comprises of two six- membered rings which are abridged together through a network of C–N, N–N and C–N bonds. There are three keto functional groups and two methyl groups at various locations of the molecule. The C9 atom of methyl group and O2 of the keto group are deviated significantly from the mean plane of the molecule. Both the six-membered rings are planar and it is evident from the magnitude of their exocyclic torsion angles. The molecular structure is stabilized by few intra and intermolecular hydrogen bonds.     

Synthesis and characterization of diselenide crosslinked polymeric micelles via Diels–Alder click reaction

ABSTRACT

A well-defined amphiphilic block copolymer, poly (ethylene oxide)-b-(poly (furfuryl methacrylate) (PEO-b-PFMA) was prepared by single electron transfer living radical polymerization using tris(dimethylamino)ethyl amine (Me6TREN) as a ligand. The block copolymer formed sub-100 nm micelles in water with PEO as a shell and PFMA as a core. Diels–Alder click type reaction was employed to form core-crosslinked micelles using a diselenide-containing crosslinker without any catalyst. The block copolymer and micelles were characterized by gel permeation chromatography, nuclear magnetic resonance, Fourier-transform infrared spectroscopy, dynamic light scattering analysis and transmission electron microscopy. The stability of core-crosslinked micelles under reductive-oxidative condition was also investigated. The diselenide crosslinked micelles displayed good stability against extensive dilution but decomposed under the presence of hydrogen peroxide or glutathione. The redox responsive core-crosslinked micelles can be a promising carrier for drug delivery applications.     

Impulsive rotatory motion of a circular disk in a viscous fluid

Zusammenfassung Es wird eine analytische Methode für die Bestimmung der Geschwindigkeit der Strömung und der Winkelgeschwindigkeit einer kreisförmigen Scheibe gegeben, die in einer zähen, inkompressiblen Flüssigkeit einen Drehstoss erhält.

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This research was sponsored by the US. Army under contract no. DA-11-022-ORD-2059 with the University of Wisconsin.     

Classical limit of the tensor product of holomorphic discrete series representations

For three coadjoint orbits \(\mathcal {O}_1, \mathcal {O}_2\) and \(\mathcal {O}_3\) in \(\mathfrak {g}^*\) , the Corwin–Greenleaf function \(n(\mathcal {O}_1 \times \mathcal {O}_2, \mathcal {O}_3)\) is given by the number of \(G\) -orbits in \(\{(\lambda , \mu ) \in \mathcal {O}_1 \times \mathcal {O}_2 \, : \, \lambda + \mu \in \mathcal {O}_3 \}\) under the diagonal action. In the case where \(G\) is a simple Lie group of Hermitian type, we give an explicit formula of \(n(\mathcal {O}_1 \times \mathcal {O}_2, \mathcal {O}_3)\) for coadjoint orbits \(\mathcal {O}_1\) and \(\mathcal {O}_2\) that meet \(\left( [\mathfrak {k}, \mathfrak {k}] + \mathfrak {p}\right) ^{\perp }\) , and show that the formula is regarded as the ‘classical limit’ of a special case of Kobayashi’s multiplicity-free theorem (Progr. Math. 2007) in the branching law to symmetric pairs.     

Transformation of Acetaminophen by Dichromate Oxidation Produces the Toxicants 1,4-Benzoquinone and Ammonium Ions

The reaction of the common pain reliever acetaminophen (paracetamol, 4-acetamidophenol) with dichromate was investigated over time under conditions that simulate wastewater disinfection. The occurrence of the acetaminophen in the water bodies, especially in drinking water resources, has received considerable attentions. In situ chemical oxidation is a promising cost-effective treatment method to remove acetaminophen from water body as it degrades the drug to large extent. Experimental results indicate that the reaction is second order overall and first order with respect to both dichromate and acetaminophen, and has activation energy of 14.1 kJ/mol. The second-order rate constant ranges from 1.56 × 10^?3 to 13.4 × 10^?3 min^?1 at temperature from 35 to 65°C. The acetaminophen degradation rates can be accelerated through increasing reaction temperature and oxidant concentration. The reaction under acid conditions was slightly faster than under alkaline or neutral conditions. Two of the products were unequivocally identified as the toxic compounds 1,4-benzoquinone and ammonium ions. These results demonstrate that acetaminophen is likely to be transformed significantly into toxic product if dichromate is used as an oxidizing agent during wastewater treatment.     

Formation of methylated oxyarsenicals and thioarsenicals in wild-type and arsenic (+3 oxidation state) methyltransferase knockout mice exposed to arsenate

Arsenic (+3 oxidation state) methyltransferase (As3mt) plays a central role in the enzymatically catalyzed conversion of inorganic arsenic into methylated metabolites. Most studies of the metabolism and disposition of arsenicals following exposure to inorganic arsenic focus on the formation and fate of methylated oxyarsenicals. However, recent research has shown methylated thioarsenicals to be another important class of metabolites of inorganic arsenic. Here, we report on the presence of methylated oxy- and thioarsenicals in urine and liver from wild-type mice that efficiently methylate inorganic arsenic and from As3mt knockout mice that lack arsenic methyltransferase activity. Following a single oral dose of 0.5 mg of arsenic as arsenate/kg body weight, urine from wild-type mice contained methylated oxyarsenicals and unknown arsenicals. Further analysis identified one unknown arsenical in urine of wild-type mice as dimethylmonothioarsinic acid. In addition, another unknown arsenical in urine of wild-type mice that occurred in the urine of about 20 % of arsenate-treated mice. The presence of low levels of methylated arsenicals in liver digests of As3mt knockout mice may reflect the activity of other methyltransferases or the absorption of methylated arsenicals formed by the microbiota of the gastrointestinal tract. The lack of methylated thioarsenicals in urine of As3mt knockout mice suggests a close link between the processes that form methylated oxy- and thioarsenicals.     

Investigations on Hydrolytic Activities from Stachybotrys microspora and Their Use as an Alternative in Yeast DNA Extraction

Stachybotrys microspora is a filamentous fungus characterized by the secretion of multiple hydrolytic activities (cellulolytic and non-cellulolytic enzymes). The production of these biocatalysts was studied under submerged culture using glucose, cellulose, and wheat bran as carbon sources. Endoglucanases, pectinases, xylanases, β-glucanases, chitinases, and proteases were induced on cellulose-based medium and repressed on glucose in both strains with higher amounts produced by the mutant. β-glucosidases were roughly equally produced by both strains under glucose and cellulose conditions. The yield of chitinases, β-glucanases, and proteases produced by Stachybotrys strains was as much higher than the commercialized lysing enzyme called “zymolyase,” currently used in yeast DNA extraction. In this context, we showed that S. microspora hydrolases can be successfully applied in the extraction of yeast DNA.     

Identification of Novel Natural Inhibitors to Human 3-Phosphoglycerate Dehydrogenase (PHGDH) for Cancer Treatment

Targeting the serine biosynthesis pathway enzymes has turned up as a novel strategy for anti-cancer therapeutics. 3- Phosphoglycerate dehydrogenase (PHGDH) is the rate-limiting enzyme that catalyzes the conversion of 3-Phosphoglyceric acid (3-PG) into 3-Phosphohydroxy pyruvate (3-PPyr) in the first step of serine synthesis pathway and perform a critical role in cancer progression. PHGDH has been reported to be overexpressed in different types of cancers and emerged as a novel target for cancer therapeutics. During this study, virtual screening tools were used for the identification of inhibitors of PHGDH. A library of phenolic compounds was docked against two binding sites of PHGDH using Molegro Virtual Docker (MVD) software. Out of 169 virtually tested compounds, Salvianolic acid C and Schizotenuin F possess good binding potential to co-factor binding site of PHGDH while Salvianolic acid I and Chicoric acid were identified as the best binding compounds toward the substrate binding site of PHGDH. The top selected compounds were evaluated for different physiochemical and ADMET properties, the obtained results showed that none of these hit compounds violated the Pfizer Rule and they possess acceptable ADMET profiles. Further, a commercially available hit compound, Chicoric acid, was evaluated for its anti-cancer potential against PHGDH-expressing gastric cancer cell lines (MGC-803 and SGC-7901) as well as cell lines with low expression of PHGDH (MCF-7 and MDA-MB2-31), which demonstrated that Chicoric acid possesses selective cytotoxicity toward PHGDH expressing cancer cell lines. Thus, this study has unveiled the potential of phenolic compounds, which could serve as novel candidates for the development of PHGDH inhibitors as anti-cancer agents.