J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, and Center for Complex Molecular Systems and Biomolecules, 182 23 Prague 8, Czech Republic
Properties of isolated intercalators (ethidium (E), daunomycin (D), ellipticine (EL) and 4,6'-diaminido-2-phenylidone (DAPI)) and their stacking interactions with adenine…thymine (AT) and guanine…cytosine (GC) nucleic acid base pairs were investigated by means of a nonempirical correlated ab initio method . All intercalators exhibit large charge delocalization and neither of them (including dicationic DAPI) exhibit a site with dominant charge. All intercalators have large polarizability and are good electron acceptors while base pairs are good electron donors. MP2/6-31G*(0.25) stabilization energies of complexes intercalator…base pair are large (E…AT : 22.4 kcal/mol; D…GC :17.8 kcal/mol; EL…GC :18.2 kcal/mol; DAPI…GC :21.1 kcal/mol) and are well reproduced by modified AMBER potential (vdW radii of intercalator atoms are enlarged and their vdW energy depths are increased). Standard AMBER potential give less satisfactory results especially for DAPI containing complexes. Because DAPI is the best electron acceptor (among all intercalators studied) this difference is explained by the importance of the charge transfer term which is not included in the AMBER potential. The Hartree-Fock and DFT/B3LYP methods not covering the dispersion energy fail completely to describe any energy minimum at the potential energy curve of the E…AT complex and these methods thus cannot be recommended for a study of intercalation process. On the other hand, a modified version of DFT method which covers London dispersion energy yields for all complexes very good stabilization energies well comparable with referenced ab initio data. Besides vertical dependence of interaction energy twist dependence of interaction energy was also investigated by both, reference correlated ab initio method as well as empirical potentials. It is concluded that despite the charged (E +1, D +1, DAPI +2) or polar (EL) character of intercalators investigated it is the dispersion energy which predominantly contributes to the stability of intercalator…DNA base pair complexes. Any procedure which does not cover dispersion energy is thus not suitable for studying the process of intercalation.
 D. Řeha, M. Kabeláč, F. Ryjáček, J. Šponer, J. E. Šponer, M. Elstner, S. Suhai,
P. Hobza, J. Am. Chem. Soc., 124 (2002) 3366-3376.