Differentiation of isobaric compounds using chemical ionization reaction mass spectrometry

The technique of proton transfer reaction mass spectrometry (PTR-MS) couples a proton transfer reagent, usually H3O+, with a drift tube and mass spectrometer to determine concentrations of volatile organic compounds. Here we describe a first attempt to use chemical ionization (CI) reagents other than proton transfer species inside a PTR-MS instrument. The ability to switch to other types of CI reagents provides an extra dimension to the technique. This capability is demonstrated by focusing on the ability to distinguish several isobaric aldehydes and ketones, including the atmospherically important molecules methacrolein and methyl vinyl ketone. Two CI reagents were selected, H3O+ and NO+, both being cleanly generated in a low intensity radioactive source prior to injection into the drift tube. By recording spectra with both of these reagents, the contributions from different isobaric molecules can be separated by virtue of their unique spectrometric 'fingerprints'. The work demonstrates that this form of instrumentation is not restricted to proton transfer reagents and is the basis of a more general technique, chemical ionization reaction mass spectrometry (CIRMS).     

On the Dual Phosphorescence of Xanthone and Chromone in Glassy Hydrocarbon Hosts

Trace quantities of hydrogen‐bonding impurities in otherwise highly purified and dried glassy hydrocarbon matrices at 77 K can modify the relative triplet state energy levels, and hence the photophysical properties of two aromatic ketones, xanthone and chromone, to the extent that the intrinsic spectroscopic properties are obscured. The intrinsic spectroscopic properties of each are revealed in multicrystalline n‐alkane Shpol'skii matrices, and also can be observed in rigorously purified and dried hydrocarbon glasses at 77 K. The extreme sensitivity to stoichiometric, and even substoichiometric quantities of hydrogen‐bonding impurities arises from the near‐degeneracy of the two lowest‐lying triplet states, and the sensitive nature of the n→π* blueshift phenomena to specific hydrogen‐bonding interactions.     

First natural analogs of the cytotoxic thiodepsipeptide thiocoraline A from a marine Verrucosispora sp

A marine Verrucosispora sp. isolated from the sponge Chondrilla caribensis f. caribensis was found to produce thiocoraline, a potent cytotoxic compound. Five new analogs of thiocoraline were isolated and represent the first analogs of thiocoraline. 22'-Deoxythiocoraline (2), thiochondrilline C (5), and 12'-sulfoxythiocoraline (6) demonstrated significant cytotoxicity against the A549 human cancer cell line with EC(50) values of 0.13, 2.86, and 1.26 μM, respectively. The analogs provide insight into the SAR and biosynthesis of thiocoraline. The DP4 probability method was used to analyze ab initio NMR calculations to confirm stereochemical assignments.     

Microtermolides A and B from termite-associated Streptomyces sp. and structural revision of vinylamycin

Microtermolides A (1) and B (2) were isolated from a Streptomyces sp. strain associated with fungus-growing termites. The structures of 1 and 2 were determined by 1D- and 2D-NMR spectroscopy and high-resolution mass spectrometry. Structural elucidation of 1 led to the re-examination of the structure originally proposed for vinylamycin (3). Based on a comparison of predicted and experimental (1)H and (13)C NMR chemical shifts, we propose that vinylamycin's structure be revised from 3 to 4.     

Structure elucidation of uniformly 13C labeled small molecule natural products

Utilization of ²H, ¹³C, and ¹⁵N isotopically labeled proteins and peptides is now routine in biomolecular NMR investigations. The widespread availability of inexpensive, uniformly ¹³C enriched glucose now makes it possible to isolate uniformly ¹³C labeled natural products from microbial fermentation. We now wish to describe an approach for the rapid structural characterization of uniformly ¹³C labeled natural products that avoids the pitfalls of relying on parameters typically employed in biomolecular NMR studies. Copyright © 2015 John Wiley & Sons, Ltd.     

Forazoline A: Marine‐Derived Polyketide with Antifungal In Vivo Efficacy

Forazoline A, a novel antifungal polyketide with in vivo efficacy against Candida albicans, was discovered using LCMS‐based metabolomics to investigate marine‐invertebrate‐associated bacteria. Forazoline A had a highly unusual and unprecedented skeleton. Acquisition of ¹³C–¹³C gCOSY and ¹³C–¹⁵N HMQC NMR data provided the direct carbon–carbon and carbon–nitrogen connectivity, respectively. This approach represents the first example of determining direct ¹³C–¹⁵N connectivity for a natural product. Using yeast chemical genomics, we propose that forazoline A operated through a new mechanism of action with a phenotypic outcome of disrupting membrane integrity.     

Bacterial Autoimmune Drug Metabolism Transforms an Immunomodulator into Structurally and Functionally Divergent Antibiotics

Tapinarof is a stilbene drug that is used to treat psoriasis and atopic dermatitis, and is thought to function through regulation of the AhR and Nrf2 signaling pathways, which have also been linked to inflammatory bowel diseases. It is produced by the gammaproteobacterial Photorhabdus genus, which thus represents a model to probe tapinarof structural and functional transformations. We show that Photorhabdus transforms tapinarof into novel drug metabolism products that kill inflammatory bacteria, and that a cupin enzyme contributes to the conversion of tapinarof and related dietary stilbenes into novel dimers. One dimer has activity against methicillin‐resistant Staphylococcus aureus (MRSA) and vancomycin‐resistant Enterococcus faecalis (VRE), and another undergoes spontaneous cyclizations to a cyclopropane‐bridge‐containing hexacyclic framework that exhibits activity against Mycobacterium. These dimers lack efficacy in a colitis mouse model, whereas the monomer reduces disease symptoms.     

Total radical yields from tropospheric ethene ozonolysis

The gas-phase reactions of ozone with alkenes can be significant sources of free radicals (OH, HO(2) and RO(2)) in the Earth's atmosphere. In this study the total radical production and degradation products from ethene ozonolysis have been measured, under conditions relevant to the troposphere, during a series of detailed simulation chamber experiments. Experiments were carried out in the European photoreactor EUPHORE (Valencia, Spain), utilising various instrumentation including a chemical-ionisation-reaction time-of-flight mass-spectrometer (CIR-TOF-MS) measuring volatile organic compounds/oxygenated volatile organic compounds (VOCs/OVOCs), a laser induced fluorescence (LIF) system for measuring HO(2) radical products and a peroxy radical chemical amplification (PERCA) instrument measuring HO(2) + ΣRO(2). The ethene + ozone reaction system was investigated with and without an OH radical scavenger, in order to suppress side reactions. Radical concentrations were measured under dry and humid conditions and interpreted through detailed chemical chamber box modelling, incorporating the Master Chemical Mechanism (MCMv3.1) degradation scheme for ethene, which was updated to include a more explicit representation of the ethene-ozone reaction mechanism.The rate coefficient for the ethene + ozone reaction was measured to be (1.45 ± 0.25) × 10(-18) cm(3) molecules(-1) s(-1) at 298 K, and a stabilised Criegee intermediate yield of 0.54 ± 0.12 was determined from excess CO scavenger experiments. An OH radical yield of 0.17 ± 0.09 was determined using a cyclohexane scavenger approach, by monitoring the formation of the OH-initiated cyclohexane oxidation products and HO(2). The results highlight the importance of knowing the [HO(2)] (particularly under alkene limited conditions and high [O(3)]) and scavenger chemistry when deriving radical yields. An averaged HO(2) yield of 0.27 ± 0.07 was determined by LIF/model fitting. The observed yields are interpreted in terms of branching ratios for each channel within the postulated ethene ozonolysis mechanism.