Cation-templated self-assembly of a lipophilic deoxyguanosine: Solution structure of a K+-dG8 octamer

The lipophilic nucleoside 3',5'-didecanoyl-2'-deoxyguanosine, dG 1, extracts potassium salts from water into organic solvents. The K+ extraction drives the self-association of dG 1 to give G-quartet structures. A series of 1H NMR experiments indicates that the identity of the assembled species in CDCl3 is modulated by the amount of K+ extracted by dG 1. At an 8:1 dG 1 to K+ picrate ratio, the octamer (dG 1)8-K+ predominates in solution. The (dG 1)8-K+ supramolecular complex, formed by coordination of a single K+ ion by eight dG 1 monomers, is robust and structurally unique. The 1H NMR chemical shifts for both the exchangeable and nonexchangeable protons of (dG 1)8-KI in CDCl3 were assigned from a combination of 2D 1H-1H and 13C- 1H correlation experiments. One set of 1H NMR signals corresponds to a dG 1 nucleoside with an anti conformation about the C(1')N(9) glycosidic bond, whereas the other set of signals is due to 50% of the didecanoyl dG 1 adopting a syn conformation. Although the possible arrangements of an octamer containing a 1:1 ratio of anti dG 1 to syn dG 1 are many, the present NMR analysis leads to a defined single species composed of two G-quartets. In one tetramer, all of the dG 1 components have a syn conformation about the C(1')- N(9) glycosidic bond, while the other tetramer has an 'all-anti' conformation. Moreover, intertetramer NOEs are consistent with stacking of the 'all-anti' tetramer in a 'head-to-tail' orientation on top of the 'all- syn' tetramer, thus sandwiching a central K+ ion. This solution structure is, to our knowledge, different from all of the assembled structures described so far for guanine aggregates. Presumably, the K+-bound octamer represents the first observable stage of the assembly process in the aggregation of dG 1.