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.