Intermediates in Friedel-Crafts Acylation of Fumaryl Halides

Fumaryl chloride and fluoride were reacted with different Lewis acids to synthesize the intermediates of the Friedel-Crafts acylation. The salt of the monoacyl cation [C4H2FO2](+)[Sb3F16](-) was obtained from the reaction of fumaryl fluoride with SbF5 in SO2ClF solutions. The reaction was repeated using fumaryl chloride as starting material, which reacted under halogen exchange to obtain the salt of the monoacyl cation [C4H2FO2](+)[SbCl2F4](-). In addition, the reaction of fumaryl chloride with SbCl5 in SO2ClF was studied. The covalent donor-acceptor complex C4H2Cl2O2 center dot 2 SbCl5 was formed, containing oxygen-bonded Lewis acids. The compounds were characterized by low-temperature vibrational spectroscopy. Single-crystal X-ray structure analyses were conducted for [C4H2FO2](+)[Sb3F16](-) as well as for C4H2Cl2O2 center dot 2 SbCl5. In the solid state of [C4H2FO2](+)[Sb3F16](-) C center dot center dot center dot O and C center dot center dot center dot F contacts are observed and the origin of these interactions is discussed by means of ESP maps and NBO analysis. The monoacyl cation is stabilized by electrostatic attraction and electron back-donation from oxygen and fluorine ligands to the positive ring-structured pi-hole at the oxocarbenium center. Besides, the formation of the diacyl cation is not observed, which is based on small distances between the positive charges involving charge-charge repulsion. The great advantage of using fumaryl halides in Friedel-Crafts acylation is featured by the possibility to synthesize ketones keeping an acyl fluoride moiety

On the non-abelian Brumer-Stark conjecture and the equivariant Iwasawa main conjecture

We show that for an odd prime p, the p-primary parts of refinements of the (imprimitive) non-abelian Brumer and Brumer-Stark conjectures are implied by the equivariant Iwasawa main conjecture (EIMC) for totally real fields. Crucially, this result does not depend on the vanishing of the relevant Iwasawa mu-invariant. In combination with the authors' previous work on the EIMC, this leads to unconditional proofs of the non-abelian Brumer and Brumer-Stark conjectures in many new cases.Comment: 33 pages; to appear in Mathematische Zeitschrift; v3 many minor updates including new title; v2 some cohomological arguments simplified; v1 is a revised version of the second half of arXiv:1408.4934v

Stabilizing the C-N Double Bond Character in Fumaramide with the Aid of Superacids

Fumaramide was reacted with the superacidic systems XF/SbF5 and XF/BF3 (X = H, D) leading to the formation of the 0-diprotonated species. Using an equimolar amount of the Lewis acids relating to fumaramide, a mixture of the diprotonated salt and the diadduct with O-coordinated HF was obtained. The salts [C4H2X6N2O2](2+)[(BF4)(-)](2) and [C4H2X6N2O2](2)center dot[(SbF6)(-)](2) (X = H, D) were characterized by low-temperature vibrational spectro-scopy. Single-crystal X-ray structure analyses were carried out for the compounds [C4H8N2O2](2+)[(BF4)(-)](2), C4H6N2O2 center dot center dot center dot 2HF, and fumaramide. To discuss the experimental results, quantum chemical calculations were executed at the B3LYP/aug-cc-pVTZ level of theory. To investigate the impact of the protonation on the resonance + M effect and the electron distribution concern- ing the conjugated system ESP maps, NPA charges, and NBO analyses were consulted. Due to the protonation, the nitrogen lone pair contributes completely to the formation of the C=N pi-bond, stabilizing the C=N double bond character. Since no monoprotonation of fumaramide is observed, amide hydrolysis is possible simultaneously on both amide groups

On equivariant characteristic ideals of real classes

Let $p$ be an odd prime, $F/{\Bbb Q}$ an abelian totally real number field, $F_\infty/F$ its cyclotomic ${\Bbb Z}_p$-extension, $G_\infty = Gal (F_\infty / {\Bbb Q}),$ ${\Bbb A} = {\Bbb Z}_p [[G_\infty]].$ We give an explicit description of the equivariant characteristic ideal of $H^2_{Iw} (F_\infty, {\Bbb Z}_p(m))$ over ${\Bbb A}$ for all odd $m \in {\Bbb Z}$ by applying M. Witte's formulation of an equivariant main conjecture (or "limit theorem") due to Burns and Greither. This could shed some light on Greenberg's conjecture on the vanishing of the $\lambda$-invariant of $F_\infty/F.

Comparison of established and emerging biodosimetry assays

Rapid biodosimetry tools are required to assist with triage in the case of a large-scale radiation incident. Here, we aimed to determine the dose-assessment accuracy of the well-established dicentric chromosome assay (DCA) and cytokinesis-block micronucleus assay (CBMN) in comparison to the emerging γ-H2AX foci and gene expression assays for triage mode biodosimetry and radiation injury assessment. Coded blood samples exposed to 10 X-ray doses (240 kVp, 1 Gy/min) of up to 6.4 Gy were sent to participants for dose estimation. Report times were documented for each laboratory and assay. The mean absolute difference (MAD) of estimated doses relative to the true doses was calculated. We also merged doses into binary dose categories of clinical relevance and examined accuracy, sensitivity and specificity of the assays. Dose estimates were reported by the first laboratories within 0.3-0.4 days of receipt of samples for the γ-H2AX and gene expression assays compared to 2.4 and 4 days for the DCA and CBMN assays, respectively. Irrespective of the assay we found a 2.5-4-fold variation of interlaboratory accuracy per assay and lowest MAD values for the DCA assay (0.16 Gy) followed by CBMN (0.34 Gy), gene expression (0.34 Gy) and γ-H2AX (0.45 Gy) foci assay. Binary categories of dose estimates could be discriminated with equal efficiency for all assays, but at doses ≥1.5 Gy a 10% decrease in efficiency was observed for the foci assay, which was still comparable to the CBMN assay. In conclusion, the DCA has been confirmed as the gold standard biodosimetry method, but in situations where speed and throughput are more important than ultimate accuracy, the emerging rapid molecular assays have the potential to become useful triage tools

Diagnosis of Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis by Measurement of microRNA Abundance in Blood and Tissue

A solid process for diagnosis could have a substantial impact on the successful treatment of pancreatic cancer, for which currently mortality is nearly identical to incidence. Variations in the abundance of all microRNA molecules from peripheral blood cells and pancreas tissues were analyzed on microarrays and in part validated by real-time PCR assays. In total, 245 samples from two clinical centers were studied that were obtained from patients with pancreatic ductal adenocarcinoma or chronic pancreatitis and from healthy donors. Utilizing the minimally invasive blood test, receiver operating characteristic (ROC) curves and the corresponding area under the curve (AUC) analysis demonstrated very high sensitivity and specificity of a distinction between healthy people and patients with either cancer or chronic pancreatitis; respective AUC values of 0.973 and 0.950 were obtained. Confirmative and partly even more discriminative diagnosis could be performed on tissue samples with AUC values of 1.0 and 0.937, respectively. In addition, discrimination between cancer and chronic pancreatitis was achieved (AUC = 0.875). Also, several miRNAs were identified that exhibited abundance variations in both tissue and blood samples. The results could have an immediate diagnostic value for the evaluation of tumor reoccurrence in patients, who have undergone curative surgical resection, and for people with a familial risk of pancreatic cancer

A Ten-microRNA Expression Signature Predicts Survival in Glioblastoma

Glioblastoma (GBM) is the most common and aggressive primary brain tumor with very poor patient median survival. To identify a microRNA (miRNA) expression signature that can predict GBM patient survival, we analyzed the miRNA expression data of GBM patients (n = 222) derived from The Cancer Genome Atlas (TCGA) dataset. We divided the patients randomly into training and testing sets with equal number in each group. We identified 10 significant miRNAs using Cox regression analysis on the training set and formulated a risk score based on the expression signature of these miRNAs that segregated the patients into high and low risk groups with significantly different survival times (hazard ratio [HR] = 2.4; 95% CI = 1.4–3.8; p<0.0001). Of these 10 miRNAs, 7 were found to be risky miRNAs and 3 were found to be protective. This signature was independently validated in the testing set (HR = 1.7; 95% CI = 1.1–2.8; p = 0.002). GBM patients with high risk scores had overall poor survival compared to the patients with low risk scores. Overall survival among the entire patient set was 35.0% at 2 years, 21.5% at 3 years, 18.5% at 4 years and 11.8% at 5 years in the low risk group, versus 11.0%, 5.5%, 0.0 and 0.0% respectively in the high risk group (HR = 2.0; 95% CI = 1.4–2.8; p<0.0001). Cox multivariate analysis with patient age as a covariate on the entire patient set identified risk score based on the 10 miRNA expression signature to be an independent predictor of patient survival (HR = 1.120; 95% CI = 1.04–1.20; p = 0.003). Thus we have identified a miRNA expression signature that can predict GBM patient survival. These findings may have implications in the understanding of gliomagenesis, development of targeted therapy and selection of high risk cancer patients for adjuvant therapy