Nuclear magnetic resonance and mass spectrometry studies of 2′,3′,5′-O-triacetylguanosine self-assembly in the presence of alkaline earth metal ions (Ca2+, Sr2+, Ba2+)

We report structural determination of cation-templated self-assembly of a guanosine derivative, 2′,3′,5′-O-triacetylguanosine (TAG), in the presence of three alkaline earth metal ions (Ca2+, Sr2+, and Ba2+) in CDCl3. Using a combination of nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESI-MS) methods, we have found that TAG molecules form discrete octamers in the form of [TAG]8M2+ (M2+ = Ca2+, Sr2+, and Ba2+), which is composed of two G-quartets and a sandwiched metal ion. We have determined the ability of the three alkaline earth metal ions to promote TAG self-assembly (relative binding affinity) to be Sr2+ ≫ Ba2+ > Ca2+. More importantly, we have used two-dimensional (2D) NMR methods to determine the structural details of [TAG]8Sr2+. In particular, we found that each octamer consists of an all-anti G-quartet stacking on top of an all-syn G-quartet in a tail-to-head fashion with a twist angle of 45° between the two G-quartets. This TAG octamer structure represents a unique case quite different from other lipophilic guanosine octamers reported in the literature.