Data-Independent Microbial Metabolomics with Ambient Ionization Mass Spectrometry

Atmospheric ionization methods are ideally suited for prolonged MS/MS analysis. Data-independent MS/MS is a complementary technique for analysis of biological samples as compared to data-dependent analysis. Here, we pair data-independent MS/MS with the ambient ionization method nanospray desorption electrospray ionization (nanoDESI) for untargeted analysis of bacterial metabolites. Proof-of-principle data and analysis are illustrated by sampling Bacillus subtilis and Pseudomonas aeruginosa directly from Petri dishes. We found that this technique enables facile comparisons between strains via MS and MS/MS plots which can be translated to chemically informative molecular maps through MS/MS networking. The development of novel techniques to characterize microbial metabolites allows rapid and efficient analysis of metabolic exchange factors. This is motivated by our desire to develop novel techniques to explore the role of interspecies interactions in the environment, health, and disease. This is a contribution to honor Professor Catherine C. Fenselau in receiving the prestigious ASMS Award for a Distinguished Contribution in Mass Spectrometry for her pioneering work on microbial mass spectrometry.

Sustainable Three‐Component Synthesis of Isothioureas from Isocyanides,Thiosulfonates, and Amines

Multiple applications of isothioureas as fine chemicals (or their precursors) are known, but a general sustainable method for their synthesis was hitherto unavailable. We report a novel general approach towards S‐alkyl and S‐aryl isothioureas through a copper(I)‐catalyzed three‐component reaction between amines, isocyanides, and thiosulfonates. The formal synthesis of a superpotent sweetener further illustrates the applicability of our method.     

Furanosyl Oxocarbenium Ion Stability and Stereoselectivity

Lewis acid mediated substitution reactions using [D]triethylsilane as a nucleophile at the anomeric center of the four pentofuranoses, ribose, arabinose, xylose, and lyxose, all proceed with good to excellent stereoselectivity to provide the 1,2‐cis adducts. To unravel the stereoelectronic effects underlying the striking stereoselectivity in these reactions we have mapped the energy landscapes of the complete conformational space of the oxocarbenium ions of the four pentofuranoses. The potential energy surface maps provide a detailed picture of the influence of the differently oriented substituents and their mutual interactions on the stability of the oxocarbenium ions and the maps can be used to account for the observed stereoselectivities of the addition reactions.     

Synthesis of novel azanorbornylpurine derivatives

Azanorbornylpurine derivatives were prepared by Mitsunobu reaction of appropriate hydroxyazanorbornane derivative with 6-chloropurine or construction of purine base at azanorbornylamines. The prepared target compounds were evaluated for antiviral activity and effect on neuronal and muscle nicotinic acetylcholine receptors.     

DFT study on H2O activation by stepped and planar Rh surfaces

In this research the effect of steps (lower coordinated surface atoms) and the presence of pre-adsorbed oxygen on the activation energy of water are studied with DFT. Without oxygen water activation is found to be structure insensitive. When oxygen is adsorbed on the surface and acts as the acceptor for the hydrogen at the step edge, the barrier will decrease significantly.     

Electron probe microanalysis of SiO2-coated minerals: Subsurface phases in quartz

Crystal fragments of biotite, garnet, and spinel were mounted together in one block which afterwards was sawn into several pieces; each piece was coated with SiO₂ of varying thickness, up to 7.9m. Electron probe microanalysis was carried out at various accelerating voltages of the major elements present, using the non-SiO₂-coated minerals as reference standard.Calibration curves, depth below the surface versus ratios of X-ray yields, have been established with the ultimate goal to use them for a (semi)-quantification of elements present in subsurface phases in quartz, a common host mineral in rocks.     

Interplay between structure and size in a critical crystal nucleus

We study the kinetics of crystal nucleation of an undercooled Lennard-Jones liquid using various path-sampling methods. We obtain the rate constant and elucidate the pathways for crystal nucleation. Analysis of the path ensemble reveals that crystal nucleation occurs along many different pathways, in which critical solid nuclei can be small, compact, and face centered cubic, but also large, less ordered, and more body centered cubic. The reaction coordinate thus includes, besides the cluster size, also the quality of the crystal structure.     

Investigation towards an efficient synthesis of benzo[g]isoquinoline-1,5,10(2H)-triones

As part of our research on 2-aza analogues of pentalongin, the active principle of Pentas longiflora Oliv., the first synthesis of 2,3-disubstituted benzo[g]isoquinoline-1,5,10(2H)-triones via 3,4-disubstituted 6-hydroxybenzo[g]furo[4,3,2-de]isoquinoline-2,5(4H)-diones as the key intermediates is reported. The latter compounds have been prepared by treating 2-methoxycarbonyl-1,4-naphthoquinone with N-substituted enaminoesters under acidic conditions. These reagents are easily accessible from readily available 1,4-dihydroxy-2-naphthoic acid, β-ketoesters and primary amines. Finally, a short synthesis of substituted benzo[g]isoquinoline-1,5,10(2H)-triones is achieved by an oxidative addition of N-substituted enaminoesters onto methyl 1,4-dihydroxynaphthalene-2-carboxylate.