DNA binding mode and sequence specificity of piperazinylcarbonyloxyethyl derivatives of anthracene and pyrene

Four novel piperazinylcarbonyloxyethyl derivatives of anthracene and pyrene have been prepared and investigated with respect to sequence specificity a nd synergism between hydrophobic and electrostatic effects upon binding to DNA. Linear and circular dichroism spectroscopy was used to assess the orie ntation of the aromatic chromophores relative to the nucleobases. Anthracen e and pyrene derivatives 2a and 3 are both concluded to bind to homo-polynu cleotide poly(dA-dT)(2) by intercalation of their aromatic moieties between base pairs, with a binding constant K-AT of 4 x 10(5) M-1 and 2 x 10(6) M- 1, respectively. Significantly reduced affinities (K-GC = 3 x 10(4) M-1 and 10(5) M-1, respectively) are observed with poly(dG-dC)(2), due to less fav orable interactions of the piperazinium tail in the minor groove. Base pair specificity is reflected in the binding thermodynamics, with the binding t o AT being more enthalpically driven than the binding to GC. Phenyl substit ution at the quaternary piperazinium site of the anthracene derivative 2b, does not affect the ratio K-AT/K-GC, but reduces the affinity for both AT E nd GC slightly. Moreover, the phenyl group in the 10-position of 4 prevents intercalation, and apparently, this compound binds externally to both AT a nd GC duplex polynucleotides. The results are discussed in terms of general features of the interactions of the intercalating and minor-groove binding molecular moieties, and their interplay with each other, with potentials f or tuning specificity.