Linear and circular dichroism of harmine and harmaline interacting with DNA

The interaction of the β-carboline derivatives harmine and harmaline with calf thymus DNA was studied using linear and circular dichroism techniques. Absorption linear dichroism in an electric field indicated that the transition moment (at 336 nm) of harmine lies at angle χ = 82° relative to the helix axis and that the same angle for harmaline (at 365 nm) is only 67°. The 82° angle found for harmine is compatible with the interpretation that the molecule is intercalated between two consecutive base pairs of the DNA. The c.d. results in the u.v. region for the DNA harmine complex support this interpretation, since the increase in the magnitude of all the DNA c.d. bands can also be explained by assuming an intercalation. Since a 67° angle was found for harmaline, an intercalation is in that case unlikely, the molecule is probably in a tilted position in one of the DNA grooves. However, harmaline can induce a conformational change in nucleic acids, as shown by the modification of the c.d. spectra of DNA and, especially, of poly[d(A-T)], the addition of harmaline to this polynucleotide gradually inducing its pre-melting at 4°C. This study shows that the hydrogenation of a double bond of the pyridine ring converting harmine to harmaline greatly alters the interactions of the molecule with DNA.