On the existence of the H3 tautomer of adenine in aqueous solution. Rationalizations based on hybrid quantum mechanics/molecular mechanics predictions

Abstract

The ¹⁵N NMR spectrum of adenine in aqueous solution has been modeled using high-level combined density functional theory/molecular mechanics techniques coupled to a dynamical averaging scheme. The explicit consideration of the three lowest-energy tautomers of adenine—H9, H7 and H3—allows for a well-founded comparison to experimental data. Based on a very good agreement between the predicted and measured ¹⁵N NMR spectrum of adenine, we have estimated the populations of the H9 and H7 tautomers to be around 83 and 17%, respectively—in good agreement with experimental data—and thus concluded that the H3 tautomer is likely not to be formed in aqueous solution. In addition to the ¹⁵N NMR spectrum we have also predicted the ¹³C NMR spectrum and ²J(¹⁵N–H) indirect spin–spin coupling constants. Finally we have calculated and rationalized the general shape of the low-resolution UV absorption spectrum of adenine in water.