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In the present study we use quantum-chemical calculations to investigate how the reactivity of vinyl sulfone-based compounds can be modified from an irreversible to a reversible reaction with thiols. Based on the predictions from theory, an array of nine different vinyl sulfones with systematically varying substitution pattern was synthesized and their crystal structures were determined. Subsequent Hirshfeld surface analyses employing the principle of electrostatic complementarity aid the understanding of the crystal packing of the synthesized compounds. Reactivity studies against the nucleophile 2-phenylethanethiol mirror the properties predicted by the quantum-chemical computations in solution. 63152 † Electronic supplementary information (ESI) available: Crystallographic details, summary of hydrogen bonds in the crystals, electrostatic potentials mapped onto the Hirshfeld surfaces of all compounds 1-9. CCDC 852449, 897056-897063. For ESI and crystallographic data in CIF or other electronic format see

Thermal desorption based enrichment is a general concept that can enhance any detection system's sensitivity and selectivity. Given their large interior surface area and chemical versatility, archetype metal–organic frameworks (MOFs) are selected for preconcentration of explosives and their precursors occurring in low concentrations, and are compared to the state‐of‐the‐art sorbent Tenax TA. Applying inverse gas chromatography (iGC), this study shows that several archetype MOFs, namely HKUST‐1 and MIL‐53, surpass Tenax regarding their specific retention volume for nitromethane, a typical ingredient in improvised explosives. Using linear hydrocarbons as reference probe molecules, the dispersive surface energy is determined for all MOFs along with the specific contribution of the nitro group for HKUST‐1 and ZIF‐8. Trends from pulse‐chromatographic iGC‐investigations are mostly followed in breakthrough and thermal desorption experiments using a 1000 ppm nitromethane source. In these experiments, HKUST‐1 proves the peak substance, with enrichment factors being 109‐fold higher than for Tenax, followed by MIL‐53. In case of HKUST‐1, this factor is successfully reproduced for a 1 ppm concentration scenario. This shows that archetype MOFs can be suitable or even superior candidates for a sensitive sensing of nitroalkane explosives from the gas phase by a concept of preconcentration.

The inhibition potencies of covalent inhibitors mainly result from the formation of a covalent bond to the enzyme during the inhibition mechanism. This class of inhibitors has essentially been ignored in previous target-directed drug discovery projects because of concerns about possible side effects. However, their advantages, such as higher binding energies and longer drug-target residence times moved them into the focus of recent investigations. While the rational design of non-covalent inhibitors became standard the corresponding design of covalent inhibitors is still in its early stages. Potent covalent inhibitors can be retrieved from large compound libraries by covalent docking approaches but protocols are missing that can reliably predict the influence of variations in the substitution pattern on the affinity and/or reactivity of a given covalent inhibitor. Hence, the wanted property profile can only be obtained from trial-and-error proceedings. This paper presents an appropriate protocol which is able to predict improved covalent inhibitors. It uses hybrid approaches, which mix quantum mechanical (QM) and molecular mechanical (MM) methods to predict variations in the reactivity of the inhibitor. They are also used to compute the required information about the non-covalent enzyme-inhibitor complex. Docking tools are employed to improve the inhibitor with respect to the non-covalent interactions formed in the binding site.