Cation-directed self-assembly of lipophilic nucleosides: the cationʹs central role in the structure and dynamics of a hydrogen-bonded assembly

This paper focuses on the cationʹs central role in controlling the self-assembly of a lipophilic nucleoside, isoguanosine (isoG) , in organic solvents. First, we use 1H NMR spectroscopy to show that a Ba2+ cation directs a mixture of the isomers isoG and guanosine (G) to self-sort into separate assemblies, without any detectable G–isoG cross-association. Next, we use electrospray ionization mass spectrometry to show that the cation controls the reversible self-assembly of isoG . Final section focuses on the dynamic exchange of components between two different assemblies, namely, a (isoG )5–Li+ pentamer and a (isoG )10–Li+ decamer. Our 1H and 7Li NMR data is consistent with a cation-filled pentamer, (isoG )5–Li+, moving as a unit during a bimolecular pentamer–decamer exchange. These data highlight crucial aspects regarding the cation-templated self-assembly of lipophilic nucleosides: (1) the structural information encoded within each nucleoside dictates the size and shape of the hydrogen-bonded assembly; (2) a cation is required to template and stabilize these discrete hydrogen-bonded assemblies, and (3) dynamic exchange of cation-filled, hydrogen-bonded units is likely to be a hallmark of these multi-layered nucleoside assemblies.