Thermodynamics of the formation of Ag(I)-mediated azole base pairs in DNA duplexes ☆

Abstract Isothermal titration calorimetry was applied to determine the thermodynamic parameters for the specific binding of Ag(I) ions to a series of DNA duplexes comprising Im:Im or Tr:Tr mispairs to form metal-mediated Im–Ag(I)–Im or Tr–Ag(I)–Tr base pairs (Im = imidazole nucleoside; Tr = 1.2,4-triazole nucleoside). A total of seven different duplexes are discussed, incorporating one to three artificial base pairs in neighboring or non-neighboring positions. The association constant related to the formation of Tr–Ag(I)–Tr base pairs is estimated to be 3  M − 1 . In contrast, Im–Ag(I)–Im base pairs are much more stable. The intrinsic association constant for their formation is in the order of 10 6  M − 1 and is therefore larger than that for the formation of T–Hg(II)–T and C–Ag(I)–C base pairs consisting of natural nucleobases. Two neighboring Im–Ag(I)–Im base pairs form cooperatively, whereas two remotely located Im–Ag(I)–Im base pairs form non-cooperatively. In general, the specific binding of Ag(I) to Im:Im-containing duplexes is enthalpically driven, with a significant additional entropic contribution in most cases.