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 st able cyclic structures of the keto tautomer of cytosine complexed with wate r 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 deproto nation enthalpies of the two NH bonds of the amino group differ by 23 kJ mo l(-1) from each other and this reflects the asymmetric deformation of the a mino group. The most stable hydrogen bond between cytosine and water is for med at the acceptor atom characterized by the lowest proton affinity and at the NH group having the highest acidity. The results are compared with dat a obtained at the same level of theory for the uracil- and thymine-water co mplexes. For the three nucleobases, the intermolecular distances and the en ergies of the hydrogen bonds formed at the different sites depend on the pr oton 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.