Nuclear magnetic resonance and computational studies of cation-directed self-assembly of guanosine derivatives

In this thesis, we document a comprehensive study of the cation-directed self-assembly of several guanosine derivatives. We have used nuclear magnetic resonance (NMR) and mass spectrometry techniques to characterize the self-assembled structures formed from 2',3',5'-O-triacetylguanosine (TAG) in the presence of Na+, K+, Rb+, Sr2+ , Ba2+, Pb2+, and La3+ in organic solvents. We found that these cations are capable of promoting the formation of a G-quartet, in which four guanine bases are held together by hydrogen bonds. Furthermore, TAG molecules form polymeric aggregates with monovalent cations but discrete octamers with divalent cations. Using two-dimensional NMR techniques, we determined that the [TAG]Sr2+ octamer is composed of an all-anti G-quartet (chi ≈ -170 ∼ -180°) stacked on top of an all-syn G-quartet (chi ≈ 60 ∼ 70°) in a "tail-to-head" orientation. Using TAG as a model, we also determined the NMR signatures for alkali metal cations residing inside the G-quartet channel: delta( 23Na) = -18.9 ppm, delta(39K) = 10.4 ppm, and delta( 87Rb) = 60.9 ppm. Quantum chemical calculations using a G4-M +-G4-M+-G4-M+-G 4 model (M = Na, K, Rb) at the Hartree-Fork level with basis sets 3-21G(d) for G4 and cc-pVTZ for M+ gave remarkable agreement between experimental and calculated chemical shielding values. This is the first time that experimental NMR assignment for this type of alkali metal ions is confirmed by quantum chemical calculations. We have also synthesized a large quantity of 17O-labeled guanosine using an enzymatic reaction. Solution and solid-state 17O NMR were performed on [6-17O]guanosine and [6-17O]TAG at 11.75 and 21.15 T. The experimental 17O NMR parameters were obtained and compared to those calculated for O6 using carefully chosen cluster models. We demonstrate that 17O NMR parameters are remarkably sensitive to hydrogen bonding and ion-carbonyl interactions. This work represents the first time that 17O NMR is used for studying G-quartet structures. Our results establish a basis for the future use of 17O NMR as a new probe in studying hydrogen-bonding and ion-ligand interactions in biomolecular systems.