Near infrared Raman spectroscopic mapping of native brain tissue and intracranial tumors

This study assessed the diagnostic potential of Raman spectroscopic mapping by evaluating its ability to distinguish between normal brain tissue and the human intracranial tumors gliomas and meningeomas. Seven Raman maps of native specimens were collected ex vivo by a Raman spectrometer with 785 nm excitation coupled to a microscope with a motorized stage. Variations within each Raman map were analyzed by cluster analysis. The dependence of tissue composition on the tissue type in cluster averaged Raman spectra was shown by linear combinations of reference spectra. Normal brain tissue was found to contain higher levels of lipids, intracranial tumors have more hemoglobin and lower lipid to protein ratios, meningeomas contain more collagen with maximum collagen content in normal meninges. One sample was studied without freezing. Whereas tumor regions did not change significantly, spectral changes were observed in the hemoglobin component after snap freezing and thawing to room temperature. The results constitute a basis for subsequent Raman studies to develop classification models for diagnosis of brain tissue.     

Self-assembly of amphiphilic hexapyridinium cations at the air/water interface and on HOPG surfaces.

Mono- and multilayers of a novel amphiphilic hexapyridinium cation with six eicosyl chains (3) are spread at the air/water interface as well as on highly ordered pyrolytic graphite (HOPG). On water, the monolayer of 3 is investigated by recording surface pressure/area and surface potential/area isotherms, and by Brewster angle microscopy (BAM). Self-organized tubular micelles with an internal edge-on orientation of molecules form at the air/water interface at low surface pressure whereas multilayers are present at high surface pressure, after a phase transition. Packing motifs suggesting a tubular arrangement of the constituting molecules were gleaned from atomic force microscopy (AFM) investigations of Langmuir-Blodgett (LB) monolayers being transferred on HOPG at different surface pressures. These LB film structures are compared to the self-assembled monolayer (SAM) of 3 formed via adsorption from a supersaturated solution, which is studied by scanning tunnelling microscopy (STM). On HOPG the SAM of 3 consists of nanorods with a highly ordered edge-on packing of the aromatic rings and an arrangement of alkyl chains which resembles the packing of molecules at the air/water interface at low surface pressure. Additional details of the molecular packing were gleaned from single-crystal X-ray structure analysis of the hexapyridinium model compound 2b, which possesses methyl instead of eicosyl residues.     

Surprising Homolytic Gas Phase Co−C Bond Dissociation Energies of Organometallic Aryl-Cobinamides Reveal Notable Non-Bonded Intramolecular Interactions

Aryl-cobalamins are a new class of organometallic structural mimics of vitamin B₁₂ designed as potential ‘antivitamins B₁₂’. Here, the first cationic aryl-cobinamides are described, which were synthesized using the newly developed diaryl-iodonium method. The aryl-cobinamides were obtained as pairs of organometallic coordination isomers, the stereo-structure of which was unambiguously assigned based on homo- and heteronuclear NMR spectra. The availability of isomers with axial attachment of the aryl group, either at the ‘beta’ or at the ‘alpha’ face of the cobalt-center allowed for an unprecedented comparison of the organometallic reactivity of such pairs. The homolytic gas-phase bond dissociation energies (BDEs) of the coordination-isomeric phenyl- and 4-ethylphenyl-cobinamides were determined by ESI-MS threshold CID experiments, furnishing (Co−C )-BDEs of 38.4 and 40.6 kcal mol⁻¹, respectively, for the two β-isomers, and the larger BDEs of 46.6 and 43.8 kcal mol⁻¹ for the corresponding α-isomers. Surprisingly, the observed (Co−C )-BDEs of the Co_β-aryl-cobinamides were smaller than the (Co−C )-BDE of Co_β-methyl-cobinamide. DFT studies and the magnitudes of the experimental (Co−C )-BDEs revealed relevant contributions of non-bonded interactions in aryl-cobinamides, notably steric strain between the aryl and the cobalt-corrin moieties and non-bonded interactions with and among the peripheral sidechains.     

“… to make Chemistry more Applicable and Generally Beneficial”—The Transition in Scientific Perspective in Eighteenth Century Chemistry

In 1751, the Swedish chemist Johan Gottschalk Wallerius first differentiated between “pure” and “applied” chemistry, a distinction which was quickly adopted by the other branches of science. Behind this was a new scientific concept of chemistry which emphasized the importance of applying chemistry's accumulated knowledge and its capabilities of providing for the general economic benefit. It also provided chemistry with a new position within the hierarchy of the sciences as well as with a new function in society. The reasons behind and causes of the change in scientific perspective associated with this concept point to the social and institutional conditions under which this field has developed into an independent academic discipline.     

Rapid and sensitive identification of epitope-containing peptides by direct matrix-assisted laser desorption/ionization tandem mass spectrometry of peptides affinity-bound to antibody beads

A method has been developed for rapid and sensitive identification of epitope-containing peptides, based on direct MALDI-MS/MS analysis of epitope-containing peptides affinity bound to affinity beads. This technique provides sequence information of the epitope that allows unambiguous identification of the epitope either by database searching or de novo sequencing. With MALDI-MS, affinity beads with bound peptides can be placed directly on the MALDI target and analyzed. Coupling a MALDI source to an orthogonal injection quadrupole time-of-flight (QqTOF) mass spectrometer allows direct sequencing of the bound peptides. In contrast to ESI-MS/MS, elution of the affinity-bound peptides followed by additional concentration and purification steps is not required, thus reducing the potential for sample loss. Direct mass spectrometric sequencing of affinity-bound peptides eliminates the need for chemical or enzymatic sequencing. Other advantages of this direct MALDI-MS/MS analysis of epitope-containing peptides bound to the affinity beads include its sensitivity (femtomole levels) and speed. In addition, direct analysis of peptides on affinity beads does not adversely affect the high mass accuracy of a QqTOF, and database searching can be performed on the MS/MS spectra obtained. In proof-of-principle experiments, this method has been demonstrated on beads containing immobilized antibodies against phosphotyrosine, the c-myc epitope tag, as well as immobilized avidin. Furthermore, de novo sequencing of epitope-containing peptides is demonstrated. The first application of this method was with anti-FLAG-tag affinity beads, where direct MALDI MS/MS was used to determine an unexpected enzymatic cleavage site on a growth factor protein.     

Studies on the Biosynthesis of Spirostaphylotrichin A

Incorporation of ¹⁴C-labelled acetate and amino acids as well as of [1-¹³C]-, [2-¹³C]-, and [1,2-¹³C₂] acetate, L -[methyl¹³C] methionine, [2,3-¹³C₂] succinate, and L -[2,3-¹³C₂] aspartate into spirostaphylotrichin A ( 1 ) by Staphylotrichum coccosporum demonstrates that the building blocks of 1 are 5 units of acetate/malonate, 1 unit of methionine, and a C₄-dicarboxylic acid. The latter is most likely aspartate and derived from the citric-acid cycle. Using [2-¹³C, 2-²H₃] acetate as a precursor, the starter unit of the polyketide chain was identified.     

Röntgenkleinwinkeluntersuchungen an Lösungen eines Polystyrolpräparates mit enger Molekulargewichtsverteilung

Zusammenfassung Es wurde das Streuverhalten von Polystyrol im thermodynamisch schlechten Lösungsmittel Cyclohexan zwischen Entmischungstemperatur und-Temperatur untersucht. Beim -Punkt und nahe dabei liegt das Verhalten eines statistisch verknäuelten Fadenmoleküls vor. Unterhalb der-Temperatur beginnt eine Aggregation. Knapp oberhalb der Entmischungstemperatur entspricht das Molekulargewicht etwa einer Verhängung zweier Fadenmoleküle. Ein Auftreten von kompakten Polymerknäueln ist bei dieser Temperatur nicht festzustellen. Der Einfluß des Fadenquerschnitts auf die Streukurve ist beträchtlich, da der Querschnitt nicht viel kleiner als die Persistenzlänge ist. Trotzdem läßt sich die Persistenzlänge (a=12,2 Å) aus dem Übergangspunkt zwischen den etwa 1/(2)² und 1/(2) proportionalen Bereichen bestimmen, da der Knick im Übergangsbereich infolge der großen Anzahl von Persistenzlängen pro Molekül sehr ausgeprägt ist.

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X-Ray small-angle investigations on solutions of a polystyrene sample with a narrow molecular weight distribution

Investigations were made of the scattering behaviour of polystyrene in the thermodynamically bad solvent cyclohexane between precipitation-temperature and-temperature. At the-point and close to it the behaviour of a statistically coiled chain molecule is found. Below-temperature an aggregation is beginning. Just above precipitation-temperature the molecular weight corresponds to an entanglement of two chain molecules. Appearance of compact polymer coils could not be noted at this temperature. The influence of the chain crosssection upon the scattering curve is considerable as the crosssection is not much smaller than the persistence length. Nevertheless, the persistence length (a=12.2 Å) may be determined from the transition point between the ranges roughly proportional to 1/(2)² and 1/(2) as the break within the transition range is very distinct on account of the great number of persistence lengths per molecule.

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Mit 3 Abbildungen

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Herrn Prof. Dr.E. Broda zum 60. Geburtstag gewidmet.     

Modular and Selective Arylation of Aryl Germanes (C−GeEt3) over C−Bpin,C−SiR3 and Halogens Enabled by Light-Activated Gold Catalysis

Selective C –C couplings are powerful strategies for the rapid and programmable construction of bi- or multiaryls. To this end, the next frontier of synthetic modularity will likely arise from harnessing the coupling space that is orthogonal to the powerful Pd-catalyzed coupling regime. This report details the realization of this concept and presents the fully selective arylation of aryl germanes (which are inert under Pd⁰/Pd^II catalysis) in the presence of the valuable functionalities C−BPin, C−SiMe₃, C−I, C−Br, C−Cl, which in turn offer versatile opportunities for diversification. The protocol makes use of visible light activation combined with gold catalysis, which facilitates the selective coupling of C−Ge with aryl diazonium salts. Contrary to previous light-/gold-catalyzed couplings of Ar–N₂⁺, which were specialized in Ar–N₂⁺ scope, we present conditions to efficiently couple electron-rich, electron-poor, heterocyclic and sterically hindered aryl diazonium salts. Our computational data suggest that while electron-poor Ar–N₂⁺ salts are readily activated by gold under blue-light irradiation, there is a competing dissociative deactivation pathway for excited electron-rich Ar–N₂⁺, which requires an alternative photo-redox approach to enable productive couplings.     

Synthesis of New,Unnatural Macrocyclic Trichothecenes: 3-isoverrucarin A ((1″-O)(3→4)abeo-verrucarin A), verrucinol,and verrucene. 46th Communication on verrucarins and roridins

A new unnatural macrocyclic trichothecene, an analogue of verrucarine A ( 1 ), which was named 3-Isoverrucarin A ((1″-O)(3→4)abeo-verrucarin A; 3 ) was synthesized starting from anguidine ( 5 ). The two key reactions were the removal of the 4β-acetoxy group of anguidine ( 5 ) by a Barton deoxygenation and the final macrolactonization. During the cyclization procedure, two unexpected new macrocyclic by-products, which were named verrucinol ( 19 ) and verrucene ( 20 ), were formed. They represent novel types of macrocyclic trichothecenes, the macrolidic moiety of verrucene ( 20 ) consisting only of the (Z,E)-muconic-acid residue. The formation of the analogous macrolide 26 of verrucene ( 20 ) was not possible, probably because the ring strain is too strong.     

The effect of pressure on hydrogen transfer reactions with quinones

The effect of pressure on the oxidation of hydroarenes 3-9 with 2,3-dichloro-5,6-dicyano-1,4-quinone (DDQ; 1 a) or o-chloranil (10), leading to the corresponding arenes, has been investigated. The activation volumes were determined from the pressure dependence of the rate constants of these reactions monitored by on-line UV/Vis spectroscopic measurements in an optical high-pressure cell (up to 3500 bar). The finding that they are highly negative and only moderately dependent on the solvent polarity (DeltaV( not equal ) = -13 to -25 in MTBE and -15 to -29 cm(3) mol(-1) in MeCN/AcOEt, 1:1) rules out the formation of ionic species in the rate-determining step and is good evidence for a hydrogen atom transfer mechanism leading to a pair of radicals in the rate-determining step, as was also suggested by kinetic measurements, studies of kinetic isotope effects, and spin-trapping experiments. The strong pressure dependence of the kinetic deuterium isotope effect for the reaction of 9,10-dihydroanthracene 5/5-9,9,10,10-D(4) with DDQ (1 a) can be attributed to a tunneling component in the hydrogen transfer. In the case of formal 1,3-dienes and enes possessing two vicinal C--H bonds, which have to be cleaved during the dehydrogenation, a pericyclic hydrogen transfer has to considered as one mechanistic alternative. The comparison of the kinetic deuterium isotope effects determined for the oxidation of tetralin 9/9-1,1,4,4-D(4)/9-2,2,3,3-D(4)/9-D(12) either with DDQ (1 a) or with thymoquinone 1 c indicates that the reaction with DDQ (1 a) proceeds in a stepwise manner through hydrogen atom transfer, analogously to the oxidations of 1,4-dihydroarenes, whereas the reaction with thymoquinone 1 c is concerted, following the course of a pericyclic hydrogen transfer. The difference in the mechanistic courses of these two reactions may be explained by the effect of the CN and Cl substituents in 1 a, which stabilize a radical intermediate better than the alkyl groups in 1 c. The mechanistic conclusions are substantiated by DFT calculations.