Competitive binding exchange between alkali metal ions (K(+), Rb(+), and Cs(+)) and Na(+) ions bound to the dimeric quadruplex [d(G(4)T(4)G(4))](2): a (23)Na and (1)H NMR study

A comparative study of the competitive cation exchange between the alkali metal ions K(+), Rb(+), and Cs(+) and the Na(+) ions bound to the dimeric quadruplex [d(G(4)T(4)G(4))](2) Was performed in aqueous solution by a combined use of the (23)Na and (1)H NMR spectroscopy. The titration data confirm the different binding affinities of these ions for the G-quadruplex and, in particular, major differences in the behavior of Cs(+) as compared to the other ions were found. Accordingly, Cs(+) competes with Na(+) only for the binding sites at the quadruplex surface (primarily phosphate groups), while K(+) and Rb(+) are also able to replace sodium ions located inside the quadruplex. Furthermore, the (1)H NMR results relative to the CsCl titration evidence a close approach of Cs(+) ions to the phosphate groups in the narrow groove of [d(G(4)T(4)G(4))](2). Based on a three-site exchange model, the (23)Na NMR relaxation data lead to an estimate of the relative binding affinity of Cs(+) versus Na(+) for the quadruplex surface of 0.5 at 298 K. Comparing this value to those reported in the literature for the surface of the G-quadruplex formed by 5'-guanosinemonophosphate and for the surface of double-helical DNA suggests that topology factors may have an important influence on the cation affinity for the phosphate groups on DNA. Copyright (C) 2009 John Wiley & Sons, Ltd.