Abstract:

An extensive analysis of trans-hydrogen bond ^2hJNN and ^1hJHN scalar couplings, the covalent ¹JHN 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 triplex. 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 ^2hJNN are observed at the triplex strand ends. Trans-hydrogen bond J correlations ( ^1hJHN) between the donor ¹H nucleus and the acceptor ¹⁵N nucleus are observed for this triplex by a novel, simple quantitative J-correlation experiment. These one-bond ^1hJHN couplings range between 1 and 3 Hz. A strong correlation is found between the chemical shift of the imino proton and the size of ^2hJNN, 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 ¹JHN 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.