Probing the cation binding modes of macrocyclic HCV Protease inhibitor BILN 2061 by multinuclear NMR

The ability of the macrocyclic HCV Protease inhibitor BILN 2061 to bind different classes of cations has been studied by 15N, 13C, and 1H NMR. 15N NMR experiments were performed at natural abundance or with isotopically labeled materials. Three classes of cations: alkali metals, alkaline earth metals, and transition metals, were examined, using two members of each class. The behavior of each cation class was found to be different, and provided insight into how metal ions interact with the molecular scaffold. These specific interactions were uncovered by examining coordination shifts, NOE correlations, and line broadening across all three nuclei.