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 MccGhee-von Hippell binding model. Binding affinities toward [poly(dA-dT)](2) were the largest for spermine-substituted naphthalimides (K-b = 2-6 x 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 intercallative, 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 pollynucleotides.