Salt-Dependent Heat Capacity Changes for RNA Duplex Formation

Two short non-self-complementary RNA duplexes have been probed extensively to assess whether the heat capacity change (Δ<i>C</i><sub>P</sub>) for RNA duplex formation is sensitive to the solution ionic strength. Isothermal titration calorimetry data for duplex formation were collected as a function of temperature to obtain the Δ<i>C</i><sub>P</sub> values under each condition. Ionic strength was varied by repeating the measurements in the presence of 0.1−1.5 M added NaCl. In both cases, the Δ<i>C</i><sub>P</sub> for duplex formation was shown to have a significant dependence on the solution ionic strength, varying linearly with the log of the added NaCl. In each case, the Δ<i>C</i><sub>P</sub> became more negative at high ionic strength. Heat capacity changes have been much better studied in the area of protein folding where Δ<i>C</i><sub>P</sub> is not strongly dependent upon ionic strength but instead depends primarily on the burial of hydrophobic surface. Whereas hydrophobic burial is almost certainly involved in RNA duplex formation as well, the polyanionic nature of the backbone and the associated ion condensation effects are almost certainly a contributor to the observed ionic strength dependence of Δ<i>C</i><sub>P</sub>s for duplex formation. These data also hint at the possibility that nearest neighbor effects may be evident in the heat capacity changes associated with nucleic acid folding.