Using Diffusion NMR To Characterize Guanosine Self‐Association: Insights into Structure and Mechanism

Abstract

This paper presents results from a series of pulsed field gradient (PFG) NMR studies on lipophilic guanosine nucleosides that undergo cation-templated assembly in organic solvents. The use of PFG-NMR to measure diffusion coefficients for the different aggregates allowed us to observe the influences of cation, solvent and anion on the self-assembly process. Three case studies are presented. In the first study, diffusion NMR confirmed formation of a hexadecameric G-quadruplex [G 1](16)4 K(+)4 pic(-) in CD(3)CN. Furthermore, hexadecamer formation from 5'-TBDMS-2',3'-isopropylidene G 1 and K(+) picrate was shown to be a cooperative process in CD(3)CN. In the second study, diffusion NMR studies on 5'-(3,5-bis(methoxy)benzoyl)-2',3'-isopropylidene G 4 showed that hierarchical self-association of G(8)-octamers is controlled by the K(+) cation. Evidence for formation of both discrete G(8)-octamers and G(16)-hexadecamers in CD(2)Cl(2) was obtained. The position of this octamer-hexadecamer equilibrium was shown to depend on the K(+) concentration. In the third case, diffusion NMR was used to determine the size of a guanosine self-assembly where NMR signal integration was ambiguous. Thus, both diffusion NMR and ESI-MS show that 5'-O-acetyl-2',3'-O-isopropylidene G 7 and Na(+) picrate form a doubly charged octamer [G 7](8)2 Na(+)2 pic(-) 9 in CD(2)Cl(2). The anion's role in stabilizing this particular complex is discussed. In all three cases the information gained from the diffusion NMR technique enabled us to better understand the self-assembly processes, especially regarding the roles of cation, anion and solvent.

Tris(pyridylmethylamino)cyclotriguaiacylene Cavitands: An Investigation of the Solution and Solid‐State Behaviour of Metallo‐Supramolecular Cages and Cavitand‐Based Coordination Polymers

“…Experimental diffusion rates obtained for two different spherical molecules in the same environment have been shown to be inversely proportional to the ratio of their radii, [29] enabling the relative size of a molecule to be estimated from a comparison of the diffusion rates. [26][27][28] This has been extended to capsule systems formed from cavitand-based ligands.…”

Ion pairing using PGSE diffusion methods

“…A hydrogen bonded molecule or anion will also be moving considerably slower than the ''free'' species. Finally, new diffusion studies concerned with varying types of aggregation involving lysozyme [82], guanosine [83], differing copper [84][85][86] and tin [87] clusters compounds, poly-amides [80], cationic half-sandwich ruthenium(II) complexes [88] and even ionic liquids [89] have all been recently published.…”

Diffusion-ordered nuclear magnetic resonance spectroscopy for analysis of DNA secondary structural elements

“…to provide MW information for samples being analyzed [32,[34][35][36][37][38][39]. Different forms of diffusion NMR experiments have been applied for diverse varieties of systems including inorganic materials [37,[40][41][42], organic molecules [17,23,24,28,[43][44][45][46][47][48][49] and polymers of different kinds (inorganic and organic polymers, polysaccharides, proteins) [21,37,[50][51][52][53][54][55][56][57][58][59][60][61][62]. Application for nucleic acids has been rather limited because the well-defined double helical structures have been investigated for most cases.…”