Molecular modeling of the binding mode of dipyrido[3,2-a:2′,3′-c] phenazine (dppz) and tetrapyrido[3,2-a:2′,3′-c:3″,2″-h:2‴,3‴-j] phenazine (tpphz) cobalt chiral metal complexes with B-DNA

In this paper, molecular modeling methods have been applied to the structural characterization of the interaction of chiral metal complexes [Co(phen)2dppz]3+{where phen=1,10-phenanthroline, dppz=dipyrido[3,2-a:2′,3′-c]phenazine} and [Co(phen)2tpphz]3+{where phen=1,10-phenanthroline, tpphz=tetrapyrido[3,2-a:2′,3′-c:3″,2″-h:2‴,3‴-j] phenazine} with the oligonucleotide (B-DNA fragment). The nature of two kinds of binding, a subject of currently controversy, has been explored. Barton et al. have proposed that there is an enantioselective DNA binding by the octahedral complexes and intercalative access by these complexes from the major groove. Norden et al. have suggested that both enantiomers bind extremely strongly to DNA from the minor groove without any noticeable enantioselectivity. Our results support and extend structural models of the minor groove based upon Norden's studies and Barton's enantioselectivity model.