Effect of alkyl chain length on self-preorganization of artificial nucleobase receptors

Abstract

Flexible receptors, having two uracil moieties connected through alkyl spacers of different lengths, exhibit intramolecular equilibria between two states in CDCl₃, CD₂Cl₂ and (CDCl₂)₂. The intramolecularly hydrogen bonded state (closed form) is shown to bind more strongly to adenine base by Watson–Crick and Hoogsteen base pairing than the non-hydrogen bonded state (open form) above 298 K. The closed forms of flexible receptors take advantage of their small entropy loss upon complexation (-2 to -37 J K^-1 mol^-1); this is understood to be due to their self-preorganization, where closed forms are structurally similar to their complexed forms. Flexible receptors show high selectivity towards the adenine base; no binding towards other natural nucleobases is observed in ¹H NMR studies. The observed selectivity shows that a hydrogen bonding system containing a base triplet is potentially a superior molecular recognition site for nucleobases compared with duplex base pair systems.