Theoretical study of the protonation and deprotonation of cytosine. Implications for the interaction of cytosine with water

The geometries, harmonic vibrational frequencies and energies of the two stable cyclic structures of the keto tautomer of cytosine complexed with water are computed using density functional theory (B3LYP) combined with the 6-31 + + G(d,p) basis set. The effect of complex formation with water on the pyramidalization of the amino group is discussed. The proton affinities of the oxygen and nitrogen atoms and the deprotonation enthalpies of the three NH bonds of cytosine are computed at the same level of theory. The deprotonation enthalpies of the two NH bonds of the amino group differ by 23 kJ mol(-1) from each other and this reflects the asymmetric deformation of the amino group. The most stable hydrogen bond between cytosine and water is formed at the acceptor atom characterized by the lowest proton affinity and at the NH group having the highest acidity. The results are compared with data obtained at the same level of theory for the uracil- and thymine-water complexes. For the three nucleobases, the intermolecular distances and the energies of the hydrogen bonds formed at the different sites depend on the proton affinity and the deprotonation enthalpy of these sites. The dominance of the proton donor capacity in determining the hydrogen-bond energies and the cooperativity in the cyclic structures are discussed. (C) 2000 Elsevier Science B.V. All rights reserved.