Effect of Tetramethylammonium Ion on the Helix-to-Coil Transition of Poly(deoxyadenylylthymidine): A Nuclear Magnetic Resonance and Calorimetric Investigation

Differential scanning calorimetry, temperaturedependent NMR, and UV spectroscopy are used to investigate the helix-to-coil transition of poly(deoxyadenylylthymidine) [poly(dA-dT)] in 1 M NaCl and 1 M Me₄NCl (tetramethylammonium chloride). All three methods reveal that the polymer has a melting temperature, t_m, that is approximately 6 °C higher in 1 M Me₄NCl than in 1 M NaCl. The NMR data show that this increased stability does not result from fundamental changes in base stacking or base pairing in going from 1 M NaCl to 1 M Me₄NCl. Consistent with this observation, the calorimetric measurements yield essentially equal enthalpies for the helix-to-coil transition under the two salt conditions (6.8 kcal per base pair in 1 M NaCl and 7.0 kcal per base pair in 1 M Me₄NCl). Analysis of the shapes of the calorimetric curves shows that the transition is more cooperative in Me₄NCl than in NaCl. Comparison of the calorimetric and van't Hoff enthalpies allows specification of the size of the cooperative unit: 27 base pairs in 1 M NaCl and 32 base pairs in 1 M Me₄NCl. The NMR data reveal that the major Me₄NCl-induced structural alterations (relative to NaCl) are a change in one glycosidic torsion angle and a partial resolution of the two phosphates. The calorimetric experiments indicate that in the absence of fortuitous compensation these conformational changes are not accompanied by a significant enthalpy effect. On the basis of these data, we suggest that in 1 M NaCl poly(dA-dT) assumes predominately a B-DNA-like conformation where the symmetry repeat occurs every base pair. By contrast, in 1 M Me4NCl the predominate conformation exhibits a dinucleotide repeat consistent with a right-handed alternating B-DNA structure.