Ultrahigh-Resolution Homo- and Heterodecoupled 1H and TOCSY NMR Experiments.

The original homonuclear decoupled (pure shift) experiments provide ultrahigh-resolution 1H spectra of compounds containing NMR-active heteronuclei of low natural isotopic abundance (e.g., 13C or 15N). In contrast, molecules containing highly abundant heteronuclei (like 31P or 19F) give doublets or a multiple of doublets in their homonuclear decoupled spectra, depending on the number of heteronuclear coupling partners and the magnitude of the respective coupling constants. In these cases, the complex and frequently overlapping signals may hamper the unambiguous assignment of resonances. Here, we present new heteronuclear decoupled (HD) PSYCHE 1H and TOCSY experiments, which result in simplified spectra with significantly increased resolution, allowing the reliable assessment of individual resonances. The utility of the experiments has been demonstrated on a challenging stereoisomeric mixture of a platinum-phosphine complex, where ultrahigh resolution of the obtained HD PSYCHE spectra made the structure elucidation of the chiral products feasible. HD PSYCHE methods can be potentially applied to other important 31P- or 19F-containing compounds in medicinal chemistry and metabolomics.

Investigation of the Molecular Details of the Interactions of Selenoglycosides and Human Galectin-3.

Human galectin-3 (hGal-3) is involved in a variety of biological processes and is implicated in wide range of diseases. As a result, targeting hGal-3 for clinical applications has become an intense area of research. As a step towards the development of novel hGal-3 inhibitors, we describe a study of the binding of two Se-containing hGal-3 inhibitors, specifically that of di(ß-D-galactopyranosyl)selenide (SeDG), in which two galactose rings are linked by one Se atom and a di(ß-D-galactopyranosyl)diselenide (DSeDG) analogue with a diseleno bond between the two sugar units. The binding affinities of these derivatives to hGal-3 were determined by 15N-1H HSQC NMR spectroscopy and fluorescence anisotropy titrations in solution, indicating a slight decrease in the strength of interaction for SeDG compared to thiodigalactoside (TDG), a well-known inhibitor of hGal-3, while DSeDG displayed a much weaker interaction strength. NMR and FA measurements showed that both seleno derivatives bind to the canonical S face site of hGal-3 and stack against the conserved W181 residue also confirmed by X-ray crystallography, revealing canonical properties of the interaction. The interaction with DSeDG revealed two distinct binding modes in the crystal structure which are in fast exchange on the NMR time scale in solution, explaining a weaker interaction with hGal-3 than SeDG. Using molecular dynamics simulations, we have found that energetic contributions to the binding enthalpies mainly differ in the electrostatic interactions and in polar solvation terms and are responsible for weaker binding of DSeDG compared to SeDG. Selenium-containing carbohydrate inhibitors of hGal-3 showing canonical binding modes offer the potential of becoming novel hydrolytically stable scaffolds for a new class of hGal-3 inhibitors.

Distinguishing between two- and three-bond correlations for all 13C multiplicities in heteronuclear NMR spectroscopy.

A novel two-dimensional method, SEA XLOC, for distinguishing between two- and three-bond correlations in heteronuclear NMR spectroscopy is introduced and demonstrated on ibuprofen and by a complete set of correlations with a simple and most complex quaternary 13C multiplet in strychnine.