The updated electrostatic potential for cytosine completes the qualitative explanations of base alkylation regiochemistry.
The relationship between the structures of different alkylating agents and the relative extents to which they modify the oxygen and nitrogen centers of nucleic acid bases has been discussed in the literature from several points of view, although each effectively attributes the increasing preference for oxygen alkylation to the increasing importance of electrostatic interactions between the reacting moieties. This is in direct contradiction to the published electrostatic potential data for cytosine which indicate the most attractive potential to lie in the vicinity of the 3-nitrogen. However, we have discovered the latter to be an artefact of the use of inadequate levels of theory. When the electrostatic potentials of cytosine are computed using more sophisticated ab initio Hartree-Fock/6-31G* calculations the global minimum does indeed lie in the vicinity of the O2-position as required by the various rationalizations of the alkylation data.
Ford
G P
GP
Department of Chemistry, Southern Methodist University, Dallas, TX 75275.
Wang
B
B
D000478:Alkylation; D003596:Cytosine / Q000737:chemistry*; D004563:Electrochemistry
D003596:Cytosine