Quantitative study on the non-covalent interactions between ATP and caffeine, theophylline and theobromine in aqueous solution

An investigation is hereby presented on the possible formation of a stacking (π–π) complex between adenosine-5′-triphosphate (ATP) and three xanthines (L), namely caffeine (Cf), theophylline (Tp) and theobromine (Tb), at different ionic strengths (0.05 ≤ I/mol L−1 ≤ 1) in NaCl(aq) and temperature (T = 283.15, 298.15 and 313.15 K), by using magnetic resonance spectroscopy 1H NMR. The values of log β of the [ATP(L)]4− species were: 1.32, 1.24 and ≤0.7 at I = 0.05 mol L−1 and T = 298.15 K for Cf, Tp and Tb, respectively. The stability constant of [ATP(Cf)]4− species shown a linear dependence on the temperature, and the values of log β obtained were: 1.18, 1.32 and 1.47 at T = 283.15, 298.15 and 313.15 K, respectively. By using the values of log β obtained at different temperatures a value of ΔH = −16 ± 3 kJ mol−1 was calculated for the formation of the stacking (π–π) complex species. The three systems were also studied potentiometrically at different ionic strengths (0.05 ≤ I/mol L−1 ≤ 1) in NaCl(aq) and T = 298.15 K. For all the investigated systems, the formation of [(ATP)(L)Hi](i−4) species (i = 1–3), with high yields (60–80%) was found; the stability trend obtained for the protonated complex species was (ATP–Tb) > (ATP–Tp) > (ATP–Cf). The stability constants of all the [(ATP)(L)Hi](i−4) species proved fairly dependent on the ionic strength that was studied by using the Debye–Hückel-type equation. Furthermore, by comparison with the stability of the species of analogous systems, such as ATP–aliphatic amines, ATP–aromatic amines and pyrophosphate–aliphatic amines, an empirical relationship between the stability of the complexes and the total basicity of the ligand was found.

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► The interaction of ATP and xanthines was studied by 1H NMR and potentiometry.
► π–π stacking was evidenced between ATP and xanthines.
► The interactions were characterized quantitatively.
► The dependence on ionic strength and on temperature was determined.