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On-line electrochemistry/liquid chromatography/mass spectrometry (EC/LC/MS) was employed to mimic the oxidative metabolism of the fungicide boscalid. High-resolution mass spectrometry and MS/MS experiments were used to identify its electrochemical oxidation products. Furthermore, the introduction of a second electrochemical cell with reductive conditions provided important additional information on the oxidation products. With this equipment, hydroxylation, dehydrogenation, formation of a covalent ammonia adduct, and dimerization were detected after initial one-electron oxidation of boscalid to a radical cation. On-line reaction with glutathione yielded different isomeric covalent glutathione adducts. The results of the electrochemical oxidation are in good accordance with previously reported in vivo experiments, showing that EC/LC/MS is a useful tool for studying biotransformation reactions of various groups of xenobiotics. (J Am Soc Mass Spectrom 2009, 20, 138 -145)

The relative stereochemistry and isomeric substitution pattern of organic molecules is typically determined using nuclear magnetic resonance spectroscopy (NMR). However, NMR spectra are sometimes nonconclusive, e.g., if spectra are extremely crowded, coupling patterns are not resolved, or if symmetry reasons preclude interpretation. Infrared spectroscopy (IR) can provide additional information in such cases, because IR represents a molecule comprehensively by depiction of the complete set of its normal vibrations. The challenge is thereby that diastereomers and substitution isomers often give rise to highly similar IR spectra, and visual distinction is insufficient and may be biased. Here we show the adaptation of an alignment algorithm, originally developed for vibrational circular dichroism (VCD) spectroscopy, to automatically match IR spectra and provide a quantitative measure of the goodness of fit, which can be used to distinguish isomers. The performance of the approach is demonstrated for different use cases: diastereomers of flexible druglike molecules, E/Z-isomers, and substitution isomers of pyrazine and naphthalene. It can be applied to IR spectra measured both in the gas phase (gas chromatography IR) and in solution.

Weighting methods applied to systems with many conformers have been broadly employed to calculate thermodynamic properties, structural characteristics, and populations. To better understand and test the sensitivity of conventional weighting methods, the conformational distributions of nicotine and its phosphorus-substituted derivatives are investigated. The weighting schemes used for this are all based on Boltzmann statistics. Classical Boltzmann factors based on the electronic energy and the Gibbs free energy are calculated at different quantum chemical levels of theory and compared to cluster weights obtained by the quantum cluster equilibrium method. Furthermore, the influence of the modified rigid-rotor–harmonic-oscillator (mRRHO) approximation on the cluster weights is investigated. The substitution of the nitrogen atom in the methylpyrrolidine ring by a phosphorus atom results in more monomer conformers and clusters being populated. The conformational distribution of the monomers remained stable at different levels of theory and weighting methods. However, going to dimers and trimers, we observe a significant influence of the level of theory, weighting method, and mRRHO cutoff on the populations of these clusters. We show that mRRHO cutoff values of 50 and 100 cm–1 yield similar results, which is why 50 cm–1 is recommended as a robust choice. Furthermore, we observe that the global minimum for ΔE 0 and ΔG varies in a few cases and that the global minimum is not always the dominantly occupied structure.

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