N -Acetyl Side-Chain Conformation in Saccharides: Solution Models Obtained from MA'AT Analysis.

MA'AT analysis has been applied to model the conformational properties of N -acetyl side-chains in biologically important GlcNAc and ManNAc monosaccharides and in a βGlcNAc-(1→4)-βGlcNAc disaccharide. Density functional theory calculations were conducted to obtain parameterized equations that relate the magnitudes and signs of 10 spin-coupling constants to conformations of the C2-N2 bonds of GlcNAc and ManNAc. Six of these equations were used with experimental J -couplings, measured in H 2 O/ 2 H 2 O and DMSO- d 6 solvents in selectively 13 C-labeled compounds, to model the C1-C2-N2-C1' torsion angle (θ 1 ) in GlcNAc and ManNAc residues. MA'AT analysis gave mean values of θ 1 of 106° for αGlcNAc and ∼116° for βGlcNAc residues, with circular standard deviations (CSDs) of 21-22° in aqueous solution, in excellent agreement with those obtained by aqueous molecular dynamics (MD) simulation. Parameter space plots revealed unique MA'AT fits of the data, and root mean squared deviations (<0.2 Hz) were twofold smaller than those back-calculated from MD models, indicating that the MA'AT models better fit the experimental J -couplings. Context effects on both θ 1 values were found to be small in a βGlcNAc-(1→4)-βGlcNAc disaccharide. MA'AT analysis gave a mean value of θ 1 of 249° for αManNAc in H 2 O/ 2 H 2 O, with a CSD of ∼19°, with both values in good agreement with MD. MA'AT models of N -acetyl side-chains are similar to those obtained previously for O -acetyl side-chains ( J. Phys. Chem. B 2017, 121, 66-77). Both O - and N -acetylation conformationally constrain the C-O or C-N bonds relative to the same bonds in unsubstituted compounds. The present work confirms the ability of MA'AT analysis to reveal relatively small changes in mean molecular torsion angles in solution and provides additional evidence of the method as an experimental tool complementary to MD simulation.