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Sequence-dependent Interactions of Cationic Naphthalimides and Polynucleotides


email: (Lisa A. Kelly)


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 (Kb = 2−6 × 106 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.