THE SELECTIVITY FOR K-ENERGIES OF HYDRATION - A THERMODYNAMIC ANALYSIS BY H-1-NMR( VERSUS NA+ IN DNA QUADRUPLEXES IS DOMINATED BY RELATIVE FREE)

We have studied the competition between Na+ and K+ for coordination by G quartets using the oligonucleotide d(G(3)T(4)G(3)) as a model syste m. d(G(3)T(4)G(3)) forms a dimeric foldback structure containing three G quartets in the presence of either NaCl or KCl. Proton chemical shi fts, which are particular to the species of coordinated ion, have been used to monitor the conversion between the sodium and potassium forms under equilibrium conditions. Analysis of titration experiments indic ates that at least two K+ are coordinated by the three quartets of the dimeric molecule, and perfect fits of the data are obtained for two N a+ being displaced by two K+ Our results also indicate that the conver sion of [d(G(3)T(4)G(3))](2) from the sodium to the potassium form is associated with a net free energy change (Delta G degrees) of -1.7 +/- 0.15 kcal/mol. It has long been suggested that the greater thermal st ability of DNA quadruplex structures in the presence of K+ is primaril y a result of the optimal fit of this ion in the coordination sites fo rmed by G quartets. However, a consideration of the relatively small c hange in free energy associated with the conversion from the sodium to the potassium form and the relatively large difference between the fr ee energy of hydration for Na+ and K+ indicates that this cannot be co rrect. Rather, the preferred coordination of K+ over Na+ is actually d riven by the greater energetic cost of Na+ dehydration with respect to K+ dehydration.