Interactions of molecules with nucleic acids. IV. Binding energies and conformations of acridine and phenanthridine compounds in the two principal and in several unconstrained dimer‐duplex intercalation sites

The binding positions and relative minimum binding energies are calculated for complexes of 9‐aminoacridine, proflavine, N‐methylphenanthridinium, and ethidium in theoretically determined intercalation sites in B‐DNA (sites I and II) and in unconstrained dimer‐duplex sites. The selection of site I in B‐DNA by these compounds agrees with the theoretical interpretation of studies of unwinding angles in closed circular DNA in all cases but ethidium, which is predicted to select site II. The most stable binding positions of the acridines and ethidium in unconstrained dimer‐duplex units agree with experimental results of intercalation complexes of dinucleoside monophosphate units. Base‐pair specificity for Watson‐Crick pairing is examined. The energy of an intercalation complex is partitioned into ΔE₂₃, the energy required to open base pairs BP₂ and BP₃ in B‐DNA to a site, and ΔE_In, the energy change when a free molecular intercalates. ΔE₂₃ depends strongly on the base‐pair sequence, whereas ΔE_In for the four molecules studied does not. The three most stable sequences contain (pyrimidine)p(purine) units, and this provides a rationale for the exclusive formation of crystals of intercalation complexes with these units. In spite of this selectivity, the distribution of GṁC and AṁT base pairs is equal for these three units and persists as the more unstable sequences are included. Therefore, specificity arises from the interaction between the base pairs and the 2′‐deoxyribose 5′‐monophosphate backbone for the opening of B‐DNA to an intercalation site and not from the interaction between the chromophore and the DNA.