An empirical analysis of proton chemical shifts in nucleic acids

We present an empirical analysis of chemical shifts for non-exchangeable protons in eleven B-form DNA duplex structures and nine other DNA oligonucleotides whose conformations have been determined from solution NMR analysis or from X-ray crystallography. The candidate structures are used to estimate the conformation-dependent part of the shift, that is, the difference between the observed shift and a reference shift found in sugars or bases. Factors influencing the choice of the appropriate reference shifts are discussed. The results indicate that a substantial portion of the observed chemical shift dispersion can be explained by ring-current theories, with smaller estimated contributions coming from electrostatic effects. The shifts of non-exchangeable base protons and of H1' are predicted better than the remaining sugar protons, but even for these latter resonances many features of the structural shifts are reproduced by a simple theory. Prospects for using proton chemical shifts in the analysis of nucleic acid structures are discussed.