DNA binding thermodynamics and sequence specificity of chiral piperazinecarbonyloxyalkyl derivatives of anthracene and pyrene

In this paper we report the DNA binding proper ties of piperazinecarbonylox y-2-propyl derivatives of anthracene (2), pyrene (3), and phenylanthracene (4). An intercalative binding mode is found for 2 and 3, while the phenyl g roup of 4 prevents intercalation and leads to external binding. Preferentia l binding of the (S)-enantiomers is found for both anthracene 2 and pyrene 3. However, the enantiomeric preference is small, with K-(R)/K-(S) being ar ound 0.5 for both the anthracene and the pyrene compounds. This is interpre ted in terms of orientation polarity in the binding, by which any intrinsic enantioselectivity is canceled by averaging of opposite binding orientatio ns. The affinities for poly(dA-dT)(2) (AT) are 10(4) M-1 for anthracene der ivative 2, and 5 x 10(5) M-1 for pyrene derivative 2. The affinities for po ly(dG-dC)(2) (GC) are I order of magnitude lower than those for AT. This is explained by steric interference of the piperazinium tail with the exocycl ic amino groups of guanine in the minor groove of GC, leading to a more sha llow intercalation in GC than in AT, as also indicated by significantly les s negative reduced linear dichroism of the intercalator absorption bands in the GC complexes. This behavior is consistent with that observed for the p reviously studied achiral analogues.(1) Binding thermodynamics support the difference in binding mode between AT and GC. The binding enthalpy of the A T complexes is significantly more negative than that of the corresponding G C complexes. This indicates a larger overlap of intercalating moiety and nu cleobases in the AT complexes, consistent with the linear dichroism results .