Cation-Templated Self-Assembly of a Lipophilic Deoxyguanosine: Solution Structure of a K-dG Octamer.

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