The acidity of uracil from the gas phase to solution: The coalescence of the N1 and N3 sites and implications for biological glycosylation

The gas-phase acidities of the N1 and N3 sites of uracil have been bracketed to provide an understanding of the intrinsic reactivity of this nucleic base. The experiments indicate that in the gas phase, the N3 site is far less acidic (Delta H-acid = 347 +/- 4 kcal mol(-1)) than the N1 site (Delta H-acid = 333 +/- 4 kcal mol(-1)), in direct contrast to in solution, where the two sites are so close in acidity as to be unresolvable. This intrinsic difference and the coalescence in solution is interpreted through gas-phase and dielectric-medium calculations. The results point to a possible chemical reason that N1 is the preferred glycosylation site in nature: nature may simply take advantage of the differential N1 and N3 acidities in a nonpolar environment to achieve selectivity.