Interactions between DNA and mono-, bis-, tris-, tetrakis-, and hexakis(aminoacridines). A linear and circular dichroism, electric orientation relaxation, viscometry, and equilibrium study

Abstract

The interaction between DNA and a series of mono-, bis-, tris-, tetrakis-, and hexakis-intercalating 9-aminoacridines has been studied with flow linear dichroism (LD), circular dichroism (CD), electric orientation relaxation (EOR) techniques, and with viscometry and equilibrium analyses. The orientation of the 9-aminoacridine ligand relative to the average orientation of the DNA bases, measured by LD, shows that with both 9-aminoacridine and the bis(acridines) the in-plane short axes of the acridine ligands are oriented perfectly parallel to the planes of the DNA bases, as expected for classical intercalation, whereas the long axes are found to be significantly tilted. This is supported by the DNA lengthening measured by EOR, which for 9-aminoacridine is 1.5 base-pair units, compared with 1.0 for ethidium bromide. Also in case of the tris(acridines) LD, CD, viscometry, and equilibrium data indicate that all acridine ligands are intercalated. The binding analysis shows an increasing degree of cooperativity in the sequence 9-aminoacridine < bis(acridines) < tris(acridines), and the corresponding binding densities, 4, 8, and 11–14, respectively, are in good agreement with those expected from the nearest-neighbor exclusion principle. The LD and CD measurements show that the tetrakis- and hexakis(acridines), despite long and flexible links, bind to DNA with only three of the acridine ligands intercalated.