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The nature of the interaction of aminoacridines and their derivatives with nucleic acidst continues to engage the attention of investigators employing many different techniques. This interest persists for various reasons. First, the aminoacridines are themselves important antibacterial and mutagenic agents. Their antibacterial action has long been the subject of intensive study1+ but in the last six years it is their ability to induce mutations, apparently by causing deletion or insertion of a single nucleotide in DKA, which has been to the f~r e .~,~ This hypothesis has been convincingly confirmed6 by amino acid sequence determinations on lysozyme altered by a double mutation which was induced by proflavine (3,Gdiaminoacridine) in bacteriophage T4. This ability to interact with DNA must also form part, at least, of the explanation of their antibacterial activity and has been associated with their inhibition of DNA-primed DNA and RNA polymerases.7*8 However, this inhibition of RNA polymerase nou-appearsg also to involve a direct inhibition of the enzyme by the aminoacridine, and, indeed, aminoacridines are known to inhibit a number of enzymes' notably those involved in oxidation-reduction reactions. So the antibacterial activity of aminoacridines is likely to depend on a wider range of effects than simply their interaction with the nucleic acids.Second, aminoacridines, on account both of their cationic charge and their three flat aromatic rings, have structural features similar to those of other compounds whose interaction with DNA is of great interest, such as carcinogens (both polycyclic hydrocarbons and benzacridines) ; certain antibiotics; nucleic acid derivatives (purines, nucleosides) ; histological dyes, e.g., those with three flat, fused rings such as pyronin, toluidine blue. and triphenylmethane dyes such as methyl green; phenanthridine trypanocides, e.g., ethidium bromide; and, of course, other acridine derivatives. many of which are noted for their antimalarial activity, e.g., atebrin.Bedfordshire, England.

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synopsisThe circular dichroihm ((31)) spectra of complexes of I)NA with ethidium bromide, proflavine, 9-aminoacridirie and 4-ethyl-9-amino-acridirie have been determined hetween 220 arid 4.70 rim, the range being extended to 600 nm for ethidium bromide. The variation of the magnitude of the visible and near--ultraviolet CD spectra of ethidium bromide-DNA complexes with the amoiint of ligand bound (7) suggests a cnmmon binding position with proflavine. On the other hand, 4-ethyl-9-aminoscridine complexed to DNA shows CD spectra not distinguishable from those of 9-aminoacridine in both the visible and ultraviolet. The interpretation of these resiilts with respect to the stereochemistry of the 1)NA-ligand complexes is discussed.