Though the reasons were not fully elicited, we suspect that that the inherent flexibility of the azobenzene core, particularly the free rotation possible about the C-N bonds, weakened the ability of this scaffold to serve as a G4 ligand. Indeed, in a related study by Zhou and workers, similar azobenzene derivatives displayed only weak G4 binding properties in physiologicallyrelevant conditions. In general, the most successful G4 binding molecules are derived from highly rigid scaffolds that allow efficient π-π stacking interactions with the planar G-tetrads.