Synthesis and characterization of water-soluble phenylene-vinylene-based singlet oxygen sensitizers for two-photon excitation

[reaction: see text] The synthesis and characterization of water-soluble singlet oxygen sensitizers with a phenylene-vinylene motif is presented. The principal motivation for this study was to better understand specific features of a water-soluble molecule that influence the photosensitized production of singlet oxygen upon nonlinear, two-photon excitation of that molecule. To achieve water solubility, sensitizers were synthesized with ionic as well as nonionic substituents. In the ionic approach, salts of N-methylated pyridine, benzothiazole, and 1-methyl-piperazine moieties were used, as were aryl-substituted sulfonic acid moieties. In the nonionic approach, aryl-substituted triethylene glycol moieties were used. Selected photophysical properties of the compounds synthesized were determined, including singlet oxygen quantum yields. Of the molecules examined, the most efficient singlet oxygen sensitizers had triethylene glycol units as the functional group that imparted water solubility. Molecules containing the ionic moieties did not make singlet oxygen in appreciable yield nor did they efficiently fluoresce. Rather, for these latter molecules, rapid charge-transfer-mediated non-radiative processes appear to dominate excited state deactivation.     

Operation of KrF and ArF tunable excimer lasers without Cassegrain optics

A commercial tunable excimer laser consists of an oscillator-amplifier combination. The oscillator produces high-quality light that is sent to the amplifier and is distributed throughout the amplifier cavity via Cassegrain optics. We describe here two alternative approaches, a single-pass configuration for use with KrF and a triple-pass configuration with ArF, both of which do away with the Cassegrain optics. In each approach, the beam energy is the same as with Cassegrain optics. For KrF, the changes provide better locking, a higher degree of linear polarization, and a better spatial beam homogeneity, but a poorer beam divergence. For ArF, there is also better beam homogeneity, but the locking efficiency and divergence are not as good as with Cassegrain optics.     

Mechanistic investigation of the 2,5-diphenylpyrrolidine-catalyzed enantioselective alpha-chlorination of aldehydes

The mechanism for the 2,5-diphenylpyrrolidine-catalyzed enantioselective alpha-chlorination of aldehydes with electrophilic halogenation reagents has been investigated by using experimental and computational methods. These studies have led us to propose a mechanism for the reaction that proceeds through an initial N-chlorination of the chiral catalyst-substrate complex, followed by a 1,3-sigmatropic shift of the chlorine atom to the enamine carbon atom. The suggested reaction course is different from previously proposed mechanisms for organocatalytic enamine reactions, in which the carbon-electrophile bond is formed directly. Furthermore, the rate-determining step in the overall reaction was determined and the presence of nonlinear effects was probed.     

AQUEOUS AGGREGATES OF BACTERIOCHLOROPHYLL c AS A MODEL FOR PIGMENT ORGANIZATION IN CHLOROSOMES

Chlorosomes isolated from Chloroflexus aurantiacus were extracted with chloroform/methanol. The extract contained bacteriochlorophylls c and a and lipids, but was devoid of proteins. This crude extract spontaneously formed aggregates when a methanol solution was dispersed in aqueous buffer. The aggregates could be sedimented by ultracentrifugation and appeared in electron micrographs as stain-excluding bodies with diameters between 70 and 170 nm. The absorption spectrum is remarkably similar to that of intact chlorosomes with an absorption maximum of bacteriochlorophyll c at around 740 nm. The circular dichroism spectrum of the aggregate is also very similar to that of intact chlorosomes. A conservative (±) band centered at 740 nm confirms the highly aggregated state of bacteriochlorophyll c in both systems. Steady-state fluorescence studies showed that in the aggregate energy-transfer from bacteriochlorophyll c to a component emitting at 830 nm took place. When the aggregate was suspended in buffer saturated with 1-hexanol the 740 nm form of bacteriochlorophyll c was reversibly converted to a form with spectral properties resembling the monomer absorbing at 670 nm but still in an aggregated state. This form of bacteriochlorophyll c showed no circular dichroism signal.     

Discovery and validation of urinary exposure markers for different plant foods by untargeted metabolomics

While metabolomics is increasingly used to investigate the food metabolome and identify new markers of food exposure, limited attention has been given to the validation of such markers. The main objectives of the present study were to (1) discover potential food exposure markers (PEMs) for a range of plant foods in a study setting with a mixed dietary background and (2) validate PEMs found in a previous meal study. Three-day weighed dietary records and 24-h urine samples were collected three times during a 6-month parallel intervention study from 107 subjects randomized to two distinct dietary patterns. An untargeted UPLC-qTOF-MS metabolomics analysis was performed on the urine samples, and all features detected underwent strict data analyses, including an iterative paired t test and sensitivity and specificity analyses for foods. A total of 22 unique PEMs were identified that covered 7 out of 40 investigated food groups (strawberry, cabbages, beetroot, walnut, citrus, green beans and chocolate). The PEMs reflected foods with a distinct composition rather than foods eaten more frequently or in larger amounts. We found that 23 % of the PEMs found in a previous meal study were also valid in the present intervention study. The study demonstrates that it is possible to discover and validate PEMs for several foods and food classes in an intervention study with a mixed dietary background, despite the large variability in such a dataset. Final validation of PEMs for intake of foods should be performed by quantitative analysis.

Synthesis of Oxacyclic Scaffolds via Dual Ruthenium Hydride/Brønsted Acid‐Catalyzed Isomerization/Cyclization of Allylic Ethers

A ruthenium hydride/Brønsted acid‐catalyzed tandem sequence is reported for the synthesis of 1,3,4,9‐tetrahydropyrano[3,4‐b]indoles (THPIs) and related oxacyclic scaffolds. The process was designed on the premise that readily available allylic ethers would undergo sequential isomerization, first to enol ethers (Ru catalysis), then to oxocarbenium ions (Brønsted acid catalysis) amenable to endo cyclization with tethered nucleophiles. This methodology provides not only an attractive alternative to the traditional oxa‐Pictet–Spengler reaction for the synthesis of THPIs, but also convenient access to THPI congeners and other important oxacycles such as acetals.     

Complex Surface Chemistry of an Otherwise Inert Solvent Molecule: Tetrahydrofuran on Si(001)

The reaction of tetrahydrofuran (THF), an otherwise inert solvent molecule, on Si(001) was experimentally studied in ultra‐high vacuum. Using scanning tunneling microscopy (STM) and photoelectron spectroscopy at variable temperature, we could both isolate a datively bound intermediate state of THF on Si(001), as well as the final configuration that bridges two dimer rows of the Si(001) surface after ether cleavage. The latter configuration implies splitting of the O?C bond, which is typically kinetically suppressed. THF thus exhibits a hitherto unknown reactivity on Si(001).     

Methods for Studying Endocytotic Pathways of Herpesvirus Encoded G Protein-Coupled Receptors

Endocytosis is a fundamental process involved in trafficking of various extracellular and transmembrane molecules from the cell surface to its interior. This enables cells to communicate and respond to external environments, maintain cellular homeostasis, and transduce signals. G protein-coupled receptors (GPCRs) constitute a family of receptors with seven transmembrane alpha-helical domains (7TM receptors) expressed at the cell surface, where they regulate physiological and pathological cellular processes. Several herpesviruses encode receptors (vGPCRs) which benefits the virus by avoiding host immune surveillance, supporting viral dissemination, and thereby establishing widespread and lifelong infection, processes where receptor signaling and/or endocytosis seem central. vGPCRs are rising as potential drug targets as exemplified by the cytomegalovirus-encoded receptor US28, where its constitutive internalization has been exploited for selective drug delivery in virus infected cells. Therefore, studying GPCR trafficking is of great importance. This review provides an overview of the current knowledge of endocytic and cell localization properties of vGPCRs and methodological approaches used for studying receptor internalization. Using such novel approaches, we show constitutive internalization of the BILF1 receptor from human and porcine γ-1 herpesviruses and present motifs from the eukaryotic linear motif (ELM) resources with importance for vGPCR endocytosis.