Sequence‐dependent Interactions of Cationic Naphthalimides and Polynucleotides

The binding interactions of three naphthalimide derivatives with heteropoly nucleic acids have been evaluated using fluorescence, absorption and circular dichroism spectroscopies. Mono‐ and bifunctionalized naphthalimides exhibit sequence‐dependent variations in their affinity toward DNA. The heteropoly nucleic acids, [Poly(dA‐dT)] 2 and [Poly(dG‐dC)] 2 , as well as calf thymus (CT) DNA, were used to understand the factors that govern binding strength and selectivity. Sequence selectivity was addressed by determining the binding constants as a function of polynucleotide composition according to the noncooperative McGhee–von Hippel binding model. Binding affinities toward [poly(dA‐dT)] 2 were the largest for spermine‐substituted naphthalimides (K b  = 2−6 × 10 6   m −1 ). The association constants for complex formation between the cationic naphthalmides and [poly(dG‐dC)] 2 or CT DNA (58% A‐T content) were 2–500 times smaller, depending on the naphthalmide–polynucleotide pair. The binding modes were also assessed using a combination of induced circular dichroism and salt effects to determine whether the naphthalimides associate with DNA through intercalative, electrostatic or groove‐binding. The results show that the monofunctionalized spermine and pyridinium‐substituted naphthalimides associate with DNA through electrostatic interactions. In contrast, intercalative interactions are predominant in the complex formed between the bifunctionalized spermine compound and all of the polynucleotides.