To understand the mechanisms that govern the many biological roles of nucleic acids, it is essential to have a complete physical description of the folding of nucleic acids. We use a combination of differential scanning calorimetry, UV spectroscopy, density, and ultrasound techniques to measure complete thermodynamic profiles for the folding/unfolding of DNA hairpins containing chemical modifications. We have characterized the unfolding thermodynamics of two sets of hairpins with sequences: d(GC N GC T5 GCGC) and d(GC N GC T5 GC M GC), where N represents a bulged base and N-M represents a W-C or mismatched base pair. Relative to the host hairpin with 4 dG-dC bp in the stem, all hairpins with a bulge or a mismatch are less stable, while the hairpins with an additional W-C base pair are more stable. The effects are enthalpy driven, indicating a loss or gain in base-pair stacking interactions, respectively. We also obtained linear enthalpy-entropy compensations with slopes of 317 K (hairpins with lesions) and 395 K (hairpins with fully paired stems); this is indicative of processes that are driven by solute-solvent interactions. The plots of apparent molar vs apparent molar adiabatic compressibility yielded slopes of 0.73 × 10 4 bar -1 (hairpins with lesions) and 0.47 × 10 4 bar -1 (hairpins with fully paired stems), in good agreement with the values of hydrophilic and hydrophobic molecules, respectively. Examples of oligomer DNA duplexes are also presented and discuss. The main conclusion is the incorporation of stabilizing chemical modifications in DNA is accompanied by an immobilization of electrostricted water while the incorporation of destabilizing modifications immobilizes structural water. Supported by Grant MCB-1912587 from NSF.
Luis A. Marky (Sun,) studied this question.