Hydrogen bonding in complexes of adenosine and 4-thiouridine: a low-temperature NMR study

Abstract

NMR experiments were performed on the association of the two sugar-protected nucleosides 2′-deoxy-4-thiouridine and 2′-deoxyadenosine in solution. Using an aprotic CDClF2–CDF3 solvent mixture, low-temperature measurements allowed the observation of individual hydrogen-bonded complexes in the slow exchange regime. 2D NOE experiments acquired at 128 K show the preferential formation of a ternary complex with two thiouridine nucleosides simultaneously bound at the Watson–Crick and Hoogsteen site of adenosine at all molar ratios. There is no indication of the 4-thiocarbonyl group involved as proton acceptor in a hydrogen bond to the adenine base to a significant extent. A more downfield chemical shift together with a smaller 1J(N,H) scalar coupling of the Watson–Crick-bound imino proton in specifically 3-15N-labeled thiouridine points to a stronger Watson–Crick than the Hoogsteen hydrogen bond. Copyright © 2001 John Wiley & Sons, Ltd.