Lipophilic G-quadruplexes are self-assembled ion pair receptors,and the bound anion modulates the kinetic stability of these complexes

With an eye toward the eventual selective modification of noncovalent structures, we used ESI-MS, X-ray crystallography, and NMR spectroscopy to study the anion's influence on the structure and dynamics of self-assembled ion pair receptors formed from guanosine G 1. We compared five complexes of formula (G 1)(16).2Ba(2+).4A(-) containing different organic anions: 2,4,6-trinitrophenolate (2), 2,6-dinitrophenolate (3), 4-methyl-2,6-dinitrophenolate (4), 4-methoxy-2,6-dinitrophenolate (5), and 2,5-dinitrophenolate (6). Crystallography reveals that anion-nucleobase hydrogen bond geometry is sensitive to both phenolate basicity and structure. For the 2,6-substituted anions 2-5, progressive shortening of anion-nucleobase hydrogen bonds is correlated with increased phenolate basicity. Lipophilic G-quadruplexes with different anions also have much different kinetic stabilities in CD(2)Cl(2) solution. Proton NMR shows that free 6 exchanges faster with G-quadruplex-bound anion than do the 2,6-dinitrophenolates 2-5. The increased lability of 6 is probably because, unlike the 2,6-dinitrophenolates, this anion cannot effectively chelate separate G(8).M(2+) octamers via anion-nucleobase hydrogen bonds. In addition to these structural effects, the anion's basicity modulates the anion exchange rate between its free and bound states. 2D EXSY NMR shows that 3 and 5 exchange about 7 times slower than the less basic picrate (2). The use of 3, a relatively basic dinitrophenolate that hydrogen bonds with the amino groups of the two "inner" G(4)-quartets, resulted in extraordinary kinetic stabilization of the G-quadruplex in CD(2)Cl(2). Thus, no isomerization product (G 1)(8).Ba(2+).(G 1)(8).Sr(2+).4(3) was observed even 2 months after the separate G-quadruplexes (G 1)(16).2Ba(2+).4(3) and (G 1)(16).2Sr(2+).4(3) were combined in CD(2)Cl(2). In sharp contrast, G-quadruplexes containing the isomeric 6 anion have isomerization half-lives of approximately t(1/2) = 30 min under identical conditions. All the evidence indicates that the structure and electronics of the organic anions, bound to the assembly's periphery, are crucial for controlling the kinetic stability of these cation-filled G-quadruplexes.