A new class of receptor molecules is presented that is highly selective for N-alkylpyridinium ions and electron-poor aromatics. Its key feature is the combination of a well-preorganized molecular clip with an electron-rich inner cavity and strategically placed, flanking bis-phosphonate monoester anions. This shape and arrangement of binding sites attracts predominantly flat electron-poor aromatics in water, binds them mainly by pi-cation, pi-pi, CH-pi, and hydrophobic interactions, and leads to their highly efficient desolvation. NAD(+) and NADP, the important cofactors of many redox enzymes, are recognized by the new receptor molecule, which embraces the catalytically active nicotinamide site and the adenine unit. Even nucleosides such as adenosine are likewise drawn into the clip's cavity. Complex formation and structures were examined by one- and two-dimensional NMR spectroscopy, Job plot analyses, and isothermal titration microcalorimetric (ITC) measurements, as well as quantum chemical calculations of (1)H NMR shifts. The new receptor molecule is a promising tool for controlling enzymatic oxidation processes and for DNA chemistry.

More than the sum of its parts: Novel hybrid compounds consisting of an organic β‐sheet‐breaking moiety and a signaling, D‐enantiomeric Aβ‐recognizing peptide moiety have been designed (see picture). The compounds, which were chemically synthesized and characterized by several techniques, combine rational design and drug selection from libraries and inhibit Aβ oligomerization and Aβ‐induced synaptic pathology.

The functionality of bioactive molecules sensitively depends on their structure. For the investigation of intrinsic structural properties, molecular beam experiments combined with laser spectroscopy have proven to be a suitable tool. Herein we present an analysis of the two isolated tripeptide model systems Ac-Phe-Tyr(Me)-NHMe and Boc-Phe-Tyr(Me)-NHMe. For this purpose, mass-selective combined IR/UV spectroscopy is applied to both substances in a molecular beam experiment. The comparison of the experimental data with DFT calculations, including different functionals as well as dispersion corrections, allows an assignment of both tripeptide models to β-turns formed independently from the protection groups and supported by the interaction of the two aromatic chromophores.

[structure: see text] Molecular clips functionalized by phosphonate or phosphate groups bind thiamine diphosphate (TPP) and S-adenosylmethionine (SAM) with high affinity in water; both sulfur-based cofactors transfer organic groups to biomolecules. For TPP, various analytical tools point toward a simultaneous insertion of both heterocyclic rings into the electron-rich clip cavity. Similarly, SAM is also embedded with its sulfonium moiety inside the receptor cavity. This paves the way for enzyme models and direct interference with enzymatic processes.

Molecular tweezers and clips of type 1−3 substituted with OAc, OH, OCONHPh, OMe, OCH 2 COOR and OCH 2-CONHR groups in the central spacer units have been synthesized by modification, by standard methods, either of the known diacetoxy-substituted derivatives 1b, 2b and 3b, or of the correspondingly substituted bis-dienophiles 4b and 5b. The synthesis of the dimethoxy-diacetoxy-substituted tweezer 1d could be accomplished through pressure-induced repetitive Diels−Alder reactions between the bis-dienophile 4b and the newly prepared diene 6b and subsequent DDQ oxidation. The thermodynamic parameters (K a and ∆G) of complex formation between the new receptors and aromatic substrates such as DCNB 21, TCNB 22, TCNQ 24 and Kosower salt 25 and the maximum complexation-induced 1 H NMR shifts (∆δ max. ) were determined by 1 H NMR titration experiments. It was found that the presence of substituents OH, OAc and OCONHPh in the central spacer units of the tweezers and clips 1−3 favours complex formation, whereas that of the substituents OMe, OCH 2 COOR and OCH 2 -CONHR disfavours it. This finding can be explained in terms