MA'AT Analysis of Aldofuranosyl Rings: Unbiased Modeling of Conformational Equilibria and Dynamics in Solution.

MA'AT analysis has been applied to methyl β-d-ribofuranoside ( 3 ) and methyl 2-deoxy-β-d- erythro -pentofuranoside ( 4 ) to demonstrate the ability of this new experimental method to determine multi-state conformational equilibria in solution. Density functional theory (DFT) was used to obtain parameterized equations for >20 NMR spin-coupling constants sensitive to furanose ring conformation in 3 and 4 , and these equations were used in conjunction with experimental spin-couplings to produce unbiased MA'AT models of ring pseudorotation. These models describe two-state north-south conformational exchange consistent with results obtained from traditional treatments of more limited sets of NMR spin-couplings (e.g., PSEUROT ). While PSEUROT , MA'AT , and aqueous molecular dynamics models yielded similar two-state models, MA'AT analysis gives more reliable results since significantly more experimental observables are employed compared to PSEUROT , and no assumptions are needed to render the fitting tractable. MA'AT models indicate a roughly equal distribution of north and south ring conformers of 4 in aqueous ( 2 H 2 O) solution compared to ∼80% north forms for 3 . Librational motion about the mean pseudorotation phase angles P of the preferred north and south conformers of 3 in solution is more constrained than that for 4 . The greater rigidity of the β- ribo ring may be caused by synergistic stereoelectronic effects and/or noncovalent (e.g., hydrogen-bonding) interactions in solution that preferentially stabilize north forms of 3 . MA'AT analysis of oligonucleotides and other furanose ring-containing biomolecules promises to improve current experimental models of sugar ring behavior in solution and help reveal context effects on ring conformation in more complex biologically important systems.