Slow threading intercalation of monomeric Ru(II) complexes with 10,13-diarylsubstituted dppz ligands

Threading intercalation is an unusual DNA binding mode that displays extremely slow dissociation kinetics, which is an important feature for cytotoxicity, making threading intercalating compounds interesting as model compounds in the search for new DNA binding drugs. This type of binding has for ruthenium complexes previously only been observed for complexes containing 11-substituted dipyridophenazine ligands. In this work we have synthesized and investigated the DNA binding properties of two new 10,13-diarylsubstituted dipyridophenazine ruthenium complexes, using spectroscopic techniques, and found that this substitution pattern provides a new strategy for development of drugs with slow dissociation kinetics. However, the nature of the aryl substituents largely affects the binding properties of the complexes as it was found that a dithienyl substituted complex exhibit slow dissociation kinetics characteristic for threading intercalation while its diphenyl substituted analogue seems to bind DNA by partial intercalation of one phenyl substituent resulting in faster dissociation.