Internucleotide scalar couplings across hydrogen bonds in Watson-Crickand Hoogsteen base pairs of a DNA triplex

An extensive analysis of trans-hydrogen bond (2h)J(NN) and (1h)J(HN) scalar couplings, the covalent (1)J(HN) couplings, and the imino proton chemical shifts is presented for Hoogsteen-Watson-Crick T . A-T and C+. G-C triplets of an intramolecular DNA tripler. The 2hJNN coupling constants for the Watson-Crick base pairs have values ranging from 6 to 8 Hz, while the Hoogsteen base paired thymines and protonated cytidines have values of approximately 7 and 10 Hz, respectively. Distinct decreases of (2h)J(NN) are observed at the tripler strand ends. Trans-hydrogen bond J correlations ((1h)J(HN)) between the donor H-1 nucleus and the acceptor N-15 nucleus are observed for this tripler by a novel, simple quantitative J-correlation experiment. These one-bond (1h)J(HN) couplings range between 1 and 3 Hz. A strong correlation is found between the chemical shift of the imino proton and the size of (2h)J(NN), With stronger J couplings corresponding to downfield chemical shifts. A similar, but inverse correlation is found between the proton chemical shift and the (absolute) size of the covalent (1)J(HN) constant. Methods of density functional theory were used to investigate the structural requirements for scalar J coupling and magnetic shielding associated with hydrogen bonding in nucleic acid base pairs. The dependencies of these NMR parameters on hydrogen bond distances were obtained for a representative base pair fragment. The results reproduce the trans-hydrogen bond coupling effect and the experimental correlations and suggest that the NMR parameters can be used to gain important insight into the nature of the hydrogen bond.