A convenient 3-step synthesis of (R)-7-hydroxycarvone from (S)-alpha-pinene

A convenient 3-step synthesis of (R)-7-hydroxycarvone (2) has been developed starting from (S)-alpha-pinene (7), using photooxygenation, oxidation, and fragmentation reactions. An improved synthesis of epoxy alcohol 6 and an unusual Ti(OiPr)(4) catalyzed hydroxy epoxide to keto alcohol rearrangement are also described.     

Requirement of aggregation propensity of Alzheimer amyloid peptides for neuronal cell surface binding

Background  

Aggregation of the amyloid peptides, Aβ40 and Aβ42, is known to be involved in the pathology of Alzheimer's disease (AD). Here we investigate the relationship between peptide aggregation and cell surface binding of three forms of Aβ (Aβ40, Aβ42, and an Aβ mutant).     

A strategy for identification of drug metabolites from dried blood spots using triple-quadrupole/linear ion trap hybrid mass spectrometry

Discovery stage studies that address issues of absorption, distribution, metabolism and excretion (ADME) are vital for lead optimization resulting in new drug candidates. Often pharmacokinetics (PK) is assessed in these experiments without regard for the metabolism of the compound or the potential for metabolites to circulate in vivo. This work presents a strategy for drug level determination and detection of metabolites using dried blood spots for sample collection. Initially, metabolites are detected from microsomal incubations and characterized using tandem mass spectrometry. Data dependent enhanced MS and enhanced product ion (EMS-EPI) scanning with dynamic background subtraction was used on a hybrid quadruple linear ion trap mass spectrometer. On-the-fly background subtraction greatly improved the detection of metabolites. These data were used to build a multiple reaction monitoring (MRM) method for the parent and metabolites. MRM-EPI scanning was used to analyze the extracted dried blood spots from the PK study. Circulating metabolites were detected using MRM and their identities confirmed on the basis of fragment ion spectra collected simultaneously. The use of dried blood spots provides a means for re-analysis of PK samples for metabolite identification without the need for complex sample storage and preparation. Both parent compound and metabolite information can be collected in these studies, resulting in a savings of time and resources.     

Differences Between Consecutive Primes

Let p_n be the nth prime. Then this paper is concerned with provingthe following result on the distribution of consecutive primes. The exponent of x in this theorem improves on the work of Heath-Brownwho proved (1) with exponent . Under the Riemann hypothesisone can prove (1) with exponent .The proof of the theorem startswith the Heath-Brown–Linnik identity which leads to aformula giving the number of primes in an interval in termsof coefficients of certain Dirichlet series. I then estimatethe coefficients by using, among other things, the informationwhich can be gained from Montgomery's mean value theorem andHuxley's version of the Hal' asz lemma. Furthermore, by usingfamiliar sieve arguments I am able to discard some of the coefficientsallowing us to gain an improvement over the previous resultof Heath-Brown. 1991 Mathematics Subject Classification: 11N05.     

Some New Old-Fashioned Modular Identities

This paper uses modular functions on the theta group to derive an exact formula for the sum $$\sum\limits_{\left| j \right| \leqslant n^{{1 \mathord{\left/ {\vphantom {1 2}} \right. \kern-\nulldelimiterspace} 2}} } {\sigma \left( {n - j^2 } \right)} $$ in terms of the singular series for the number of representations of an integer as a sum of five squares. (Here σ(k) denotes the sum of the divisors of k if k is a positive integer and σ(0) =-1/24.) Several related identities are derived and discussed. Two devices are used in the proofs. The first device establishes the equality of two expressions, neither of which is a modular form, by showing that the square of their difference is a modular form. The second device shows that a certain modular function is identically zero by noting that it has more zeros than poles in a fundamental region.     

A novel precursor ion discovery method on a hybrid quadrupole orthogonal acceleration time-of-flight (Q-TOF) mass spectrometer for studying protein phosphorylation

A tandem quadrupole time-of-flight (Q-TOF) mass spectrometer has been programmed such that phosphorylated peptides can automatically be discovered and identified in a way similar to that of the use of precursor ion or neutral loss scanning, but without the need to scan the quadrupole mass filter. Instead, the method capitalizes on the innate capability of the Q-TOF to record mass spectra and product ion spectra quickly, with good sensitivity and with good mass accuracy. Alternate mass spectra, with and without fragmentation, are recorded at high and low collision energy with the quadrupole operating in wideband mode. The method of analysis is both compatible with and dependant on liquid chromatography for separation of complex mixtures. The method has been demonstrated by searching for the neutral loss of 98 Da (H3PO4) from phosphoserine and phosphothreonine residues, or for the phosphorylated immonium ion at m/z 216 from phosphotyrosine. The method also incorporates acquisition of the product ion spectrum from any candidate precursor ions, thereby allowing confirmation of the neutral loss or product ion and providing additional sequence information to assist identification of the protein and assign the site of phosphorylation.     

Refraction and absorption of light in bacterial suspensions

Summary The apparent average refractive indices of three types of microorganism in liquid suspension have been estimated by two methods. In the first, the refractive index of the aqueous suspension is measured in an interferometer, the bacterial cell volume fraction is estimated from the dilution of an added inert solute, and the refractive index of the disperse phase is calculated with the aid of a mixture rule. In the second method, optical density spectra of suspensions in several concentrated solutions of nonpenetrating solutes are measured as a function of the refractive index,n ₁, of the solution. The value ofn ₁ when the optical density,E, has its smallest value is equated to the average cell refractive index and the constants of the parabolaE (n ₁) are related to the heterogeneity of the cell population in respect to refractive index. The preliminary results obtained by the two methods are in satisfactory agreement and are consistent with the specific refractive increments of protein and nucleic acid and their concentrations in the cell. It is pointed out that measurements of optical density spectra can also give useful information concerning the number and size of cells in a suspension and their optical dispersion constants. To obtain such information, however, a spectrophotometer specially designed to exclude forward-scattered light must be used and an acceptable theory must be available. Finally, the apparent spectral absorption of clarified cell suspensions is presented and compared with spectra obtained by other methods. It is pointed out that because of refractive heterodispersity even clarified suspensions are turbid, so that this method does not provide a completely satisfactory technique for cell spectrophotometry.

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Zusammenfassung Es wurde der scheinbare mittlere Brechungsindex von 3 Typen von Mikroorganismen in flüssiger Suspension nach zwei Methoden abgeschätzt:Bei der ersten Methode wird der Brechungsindex der bisherigen Lösung in einem Interferometer gemessen. Die Volumenkonzentration der Bakterienzellen wird aus der Verdünnung mit einer zugesetzten inerten Komponente abgeschätzt. Der Brechungsindex der dispersen Phase wird mit Hilfe der Mischungsregel berechnet.Nach der 2. Methode werden Spektren der optischen Dichte der Suspensionen in verschiedenen konzentrierten Lösungen von nicht-mischbarer 2. Komponente als Funktion des Brechungsindexn ₁ gemessen. Dieser Brechungsindexn ₁ hat seinen kleinsten Wert, wenn die optische DichteE dem mittleren Brechungsindex der Zellen gleich ist, und die Konstanten der ParabelnE (n ₁) stehen in Beziehung zur Heterogenität der Zellverteilung in Bezug auf den Brechungsindex.Die vorläufig nach den beiden Methoden erhaltenen Ergebnisse stimmen befriedigend überein und sind konsistent mit den spezifischen Refractionsinkrementen von Eiweiß- und Nukleinsäure und deren Konzentrationen in der Zelle. Es sei betont, daß Messungen der optischen Dichtespektren auch gute Information über Zahl und Größe der Zellen in einer Suspension und über deren optische Dispersionskonstanten geben können. Um diese Information zu erhalten, muß jedoch speziell ein Spektrometer gebaut werden, das gestattet, das vorwärtsgestreute Licht auszuschließen. Außerdem muß eine akzeptable Theorie vorhanden sein. Schließlich wird die scheinbare Spektralabsorption von geklärten Zellsuspensionen dargelegt und mit den Spektren, die nach anderen Methoden erhalten werden, verglichen. Es ist ausgeführt, daß wegen der Heterodispersität auch geklärte Suspensionen streuen, so daß diese Methode keine vollständig befriedigende Technik für Zellspektrometrie darstellt.

     

Alkylation of Porous Silicon by Direct Reaction with Alkenes and Alkynes

The hydrogen-terminated surface of porous silicon (PS) is sufficiently reactive for the uncatalyzed hydrosilation of alkenes and alkynes. These modifications produce dramatic changes to both the physical and chemical properties of the PS.     

Facile sequencing of oligosaccharides by matrix-assisted laser desorption/ionisation on a hybrid quadrupole orthogonal acceleration time-of-flight mass spectrometer.

N-Linked oligosaccharide mixtures released from a number of standard glycoproteins were derivatised with 3-acetylamino-6-acetylaminoacridine (AA-Ac) using reductive amination. Analysis of these mixtures using an experimental matrix-assisted laser desorption/ionisation (MALDI) hybrid quadrupole orthogonal acceleration time-of-flight (Q-TOF) mass spectrometer provided detailed information about the mass distribution of the glycan derivatives. Collision-induced dissociation of the singly protonated [M + H](+) ions also gave rise to a number of product ions produced by the sequential cleavage of the glycosidic linkages. As fragmentation of the positively charged species occurred predominantly in one direction, i.e., from the non-reducing end of the glycan to the AA-Ac moiety, a considerable amount of information could be obtained with ease about the sequence in which the sugar residues were attached to one another. This derivatisation procedure and mass spectrometric methodology were applied successfully to neutral and acidic glycans released from proteins separated by gel electrophoresis.