Cation-Templated Self-Assembly of a Lipophilic Deoxyguanosine:  Solution Structure of a K⁺−dG₈Octamer

Abstract

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.

G‐Quartets 40 Years Later: From 5′‐GMP to Molecular Biology and Supramolecular Chemistry

“…[208] Depending on conditions, dG (17) [209] To better understand the transition from molecule to defined aggregate to ordered phase in organic solvents, we collaborated with Gottarelli et al to determine the NMR structure of the octamer [17] (17). [210] Remarkably, the NMR data indicated that this octamer was a single diastereomer. In one G-quartet, all dG units had a syn-glycosidic conformation, while the other tetramer had an "all-anti" conformation.…”

Guanosine‐based Hydrogen‐bonded Scaffolds: Controlling the Assembly of Oligothiophenes

“…This downfield resonance for N2-H A is characteristic of G-quartet formation where this proton is involved in the cyclic H-bonded scheme. [21] Because only one set of signals were observed, all the molecules must adopt the same conformation and the G-quartets must stack with a D 4 -symmetry (i.e., in a head-to-head or tail-to-tail manner). [22] As also observed by CD spectroscopy, the sequential addition of cryptand, acid, and base (Fig.…”

Guanosine Hydrogen‐Bonded Scaffolds: A New Way to Control the Bottom‐Up Realisation of Well‐Defined Nanoarchitectures

“…Our and Davis groups collaborated to determine the structure of the octamer 2 8 ·K + in chloroform, the first detectable intermediate in the cation-directed self-assembly of 2, by NMR spectroscopy. [16] This octameric assembly is very robust and its stability is impressive for a non-covalent assembly. The H NMR spectra, essentially temperature independent over more than 100 8C, show two sets of signals in a 1:1 ratio corresponding each to nucleosides with different glycosydic conformation (syn-like and anti-like).…”