Predicting 19F NMR Chemical Shifts: A Combined Computational and Experimental Study of a Trypanosomal Oxidoreductase–Inhibitor Complex

The absence of fluorine from most biomolecules renders it an excellent probe for NMR spectroscopy to monitor inhibitor–protein interactions. However, predicting the binding mode of a fluorinated ligand from a chemical shift (or vice versa) has been challenging due to the high electron density of the fluorine atom. Nonetheless, reliable ¹⁹F chemical-shift predictions to deduce ligand-binding modes hold great potential for in silico drug design. Herein, we present a systematic QM/MM study to predict the ¹⁹F NMR chemical shifts of a covalently bound fluorinated inhibitor to the essential oxidoreductase tryparedoxin (Tpx) from African trypanosomes, the causative agent of African sleeping sickness. We include many protein–inhibitor conformations as well as monomeric and dimeric inhibitor–protein complexes, thus rendering it the largest computational study on chemical shifts of ¹⁹F nuclei in a biological context to date. Our predicted shifts agree well with those obtained experimentally and pave the way for future work in this area.     

Catalytic Generation and Chemoselective Transfer of Nucleophilic Hydrides from Dihydrogen

Copper(I)–N-heterocyclic-carbene (NHC) complexes enabled the catalytic generation of nucleophilic hydrides from dihydrogen (H₂) and their subsequent transfer to allylic chlorides. The highly chemoselective catalyst displayed no concomitant hydrogenation reactivity; in fact, the terminal double bond formed in the hydride transfer remained intact. Switching to deuterium gas (D₂) allowed for regioselective monodeuteration with excellent isotope incorporation.     

Minimal kernels of Dirac operators along maps

Let M be a closed spin manifold and let N be a closed manifold. For maps and Riemannian metrics g on M and h on N, we consider the Dirac operator of the twisted Dirac bundle . To this Dirac operator one can associate an index in . If M is 2‐dimensional, one gets a lower bound for the dimension of the kernel of out of this index. We investigate the question whether this lower bound is obtained for generic tupels .     

Local force titration of wood surfaces by chemical force microscopy

Cellulose - Chemical force microcopy, a variation of atomic force microscopy, opened the door to visualize chemical nano-properties of various materials in their natural state. The key function of...     

Engyodontochones,Antibiotic Polyketides from the Marine Fungus Engyodontium album Strain LF069

Six new ( 2 , 4 – 8 ) and two known polyketides with a basic structure of an anthraquinone‐xanthone were isolated from mycelia and culture broth of the fungus Engyodontium album strain LF069. The structures and relative configurations of these compounds were established by spectroscopic means, and their absolute configurations were defined mainly by comparison of quantum chemical TDDFT calculated and experimental ECD spectra. Compounds 2 and 4 – 8 were given the trivial names engyodontochone A ( 2 ) and B–F ( 4 – 8 ). Compounds 5 – 8 represent the first example of a 23,28 seco‐beticolin carbon skeleton. The relative and absolute configurations of two known substances JBIR‐97/98 ( 1 ) and JBIR‐99 ( 3 ) were determined for the first time. All isolated compounds were subjected to bioactivity assays. Compounds 1 – 4 exhibited inhibitory activity against methicillin‐resistant Staphylococcus aureus (MRSA) that was 10‐fold stronger than chloramphenicol.     

DFT Study of the Molybdenum‐Catalyzed Deoxydehydration of Vicinal Diols

The mechanism of the molybdenum‐catalyzed deoxydehydration (DODH) of vicinal diols has been investigated using density functional theory. The proposed catalytic cycle involves condensation of the diol with an Mo^VI oxo complex, oxidative cleavage of the diol resulting in an Mo^IV complex, and extrusion of the alkene. We have compared the proposed pathway with several alternatives, and the results have been corroborated by comparison with the molybdenum‐catalyzed sulfoxide reduction recently published by Sanz et al. and with experimental observations for the DODH itself. Improved understanding of the mechanism should expedite future optimization of molybdenum‐catalyzed biomass transformations.