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 [1]. 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.
References:
[1] 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.