Selective Complexation of N-Alkylpyridinium Salts: Binding of NAD+ in Water

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 π–cation, π–π, CH–π, 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 1H NMR shifts. The new receptor molecule is a promising tool for controlling enzymatic oxidation processes and for DNA chemistry. 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 (e.g., the enzyme cofactors NAD+ and NADP) in water, binds them mainly by π–cation, π–π, CH–π, and hydrophobic interactions and leads to their highly efficient desolvation (an example is illustrated here).