Intercalation binding of 6‐substituted naphthothiopheneamides to DNA: Enthalpy and entropy components

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Abstract
N‐(3‐dimethylaminopropyl) naphtho [2, 1‐b] thiophene‐4‐carboxamide and the 6‐substituted methoxy, methyl, fluoro, chloro, bromo, trifluoromethyl, and cyano derivatives have been shown to bind to DNA via intercalation with binding constants in the 35–900 × 103 range at 25°C, pH 7, and [Na+] = 0.019M . Both electron‐donating and ‐withdrawing substituents enhance intercalation binding, but the binding affinity is most enhanced by the cyano substituent. Calorimetric titrations for calf thymus DNA differ dramatically from those reported for ethidium [Hopkins et al. (1990) Biopolymers Vol. 29, pp. 449–459]. Apparent enthalpy parameters (ΔHB) for intercalation are constant only at low coverage of sites and become much more positive as saturation is approached. In the plateau region, ΔHB values for the parent and the cyano‐, fluoro‐, chloro‐, and bromo‐substituted compounds are nearly the same (∼ −5.9 kcal/mol). For the methyl‐ (−6.8 kcal/mol) and methoxy‐ (−7.5 kcal/mol) substituted compounds, the ΔHB values are more exothermic than that for the un‐substituted compound, whereas ΔHB for the trifluoromethyl compound is approximately 1 kcal/mol less exothermic. The corresponding ΔSB values, corrected for mixing effects, are in the 7–15‐cal/deg/mol range and are approximately linearly related to ΔHB if the cyano derivative is excluded.