Bioanalysis of acetylcarnitine in cerebrospinal fluid by HILIC–mass spectrometry

Acetyl‐l ‐carnitine (ALCAR) is a potential biomarker for the modulation of brain neurotransmitter activity, but is also present in cerebrospinal fluid (CSF). Recent studies have utilized hydrophilic interaction liquid chromatography–tandem mass spectrometry (HILIC‐MS/MS) based assays to detect and quantify ALCAR within biofluids such as urine, plasma and serum, using various sample pretreatment procedures. In order to address the need to quantify ALCAR in CSF on a high‐throughput scale, a new and simple HILIC‐MS/MS assay has been successfully developed and validated. For rapid analysis, CSF sample pretreatment was performed via ‘dilute and shoot’ directly onto an advanced HILIC column prior to MS/MS detection. This newly developed HILIC‐MS/MS assay shows good recoveries of ALCAR without the need for chemical derivatization and multistep sample extraction procedures. The employment of this assay is suitable for the high‐throughput bioanalysis and quantification of ALCAR within the CSF of various animal models and human clinical studies. Copyright © 2015 John Wiley & Sons, Ltd.     

Synthesis and Reactivity of the First Isolated Hydrogen‐Bridged Silanol–Silanolate Anions

We report on the first examples of isolated silanol–silanolate anions, obtained by utilizing weakly coordinating phosphazenium counterions. The silanolate anions were synthesized from the recently published phosphazenium hydroxide hydrate salt with siloxanes. The silanol–silanolate anions are postulated intermediates in the hydroxide‐mediated polymerization of aryl and alkyl siloxanes. The silanolate anions are strong nucleophiles because of the weakly coordinating character of the phosphazenium cation, which is perceptible in their activity in polysiloxane depolymerization.     

Nitrostyrene Derivatives of Adenosine 5′-Glutarates Modified with an Alkyl Spacer and their inhibitory activity on epidermal growth factor receptor protein tyrosine kinase

β-Nitrostyrene derivatives of adenosine 5′-glutarates are potent and selective bisubstrate-type inhibitors of the epidermal growth factor receptor protein tyrosine kinase (EGF-R PTK). In an attempt to improve the inhibitory activity, this type of compounds was modified with alkyl spacers of varying length between the nitrostyrene and the glutaryl units. The spacers consisted of 1, 3, 4, and 5 atoms to give compounds of the benzyl, oxyethyl, oxypropyl, and oxybutyl series, respectively (Schemes 1 and 2). Adenosine 5′-esters were prepared in the benzyl and oxypropyl series only. Compared to the compounds in the parent series without spacer (IC₅₀ = 0.7–12 μM ), most of the modified compounds inhibited the EGF-R PTK only marginally or were inactive (IC₅₀ ≥ 100 μM ). The only exceptions were the free acids 19 and 20 with IC₅₀ values of ca. 5 μM . It is noteworthy that esterification of these two hydrogen glutarates with either MeOH or adenosine yielded inactive compounds, which is in contrast to the corresponding substances without spacers.     

Absolutely indecomposable symmetric matrices

Let A be a symmetric matrix of size n×n with entries in some (commutative) field K. We study the possibility of decomposing A into two blocks by conjugation by an orthogonal matrix T∈Mat_n(K). We say that A is absolutely indecomposable if it is indecomposable over every extension of the base field. If K is formally real then every symmetric matrix A diagonalizes orthogonally over the real closure of K. Assume that K is a not formally real and of level s. We prove that in Mat_n(K) there exist symmetric, absolutely indecomposable matrices iff n is congruent to 0, 1 or −1 modulo 2s.     

Über das Primzahl-Zwillingsproblem

Ohne Zusammenfassung