DFT and NMR Studies of ²J_COH, ³J_HCOH, and ³J_CCOH Spin-Couplings in Saccharides:  C−O Torsional Bias and H-Bonding in Aqueous Solution

Abstract

Density functional theory (DFT) has been used to investigate the structural dependencies of NMR spin-coupling constants (J-couplings) involving the exchangeable hydroxyl protons of saccharides. 3JHCOH, 3JCCOH, and 2JCOH values were calculated at different positions in model aldopyranosyl rings as a function of one or more torsion angles, and results support the use of a generalized Karplus equation to treat 3JHCOH involving the non-anomeric OH groups. The presence of O5 appended to the H1-C1-O1-H coupling pathway introduces asymmetry in 3JH1,O1H Karplus curves due to internal electronegative substituent effects on the gauche couplings, thus requiring separate equations to treat this coupling. 3JCCOH values depend not only on the C-C-O-H torsion angle but also on the orientation of terminal substituents on the coupled carbon, similar to 3JCOCC studied previously (Bose et al., J. Am. Chem. Soc. 1998, 120, 11158-11173). "In-plane" oxygen increased 3JCCOH by approximately 3-4 Hz, whereas "in-plane" carbon gave more modest enhancements ( approximately 1 Hz). Three Karplus equations were derived for non-anomeric 3JCCOH based on the nature and orientation of substituents on the coupled carbon. Like 3JH1,O1H, 3JC2,O1H is also subject to internal electronegative substituent effects on the gauche couplings, thus necessitating separate equations to treat this coupling. 2JCOH values were found not to be useful probes of C-O torsions as a result of their nonsystematic dependence on these torsions. Experimental measurements of 3JHCOH and 3JCCOH in doubly 13C-labeled methyl beta-lactoside 20 and its constituent 13C-labeled methyl aldopyranosides in H2O/acetone-d6 at -20 degrees C showed that some C-O torsion angles are influenced by molecular context and do not experience complete rotational averaging in solution. A strong bias in the H3-C3-O3-H torsion angle in the Glc residue of 20 favoring a gauche conformation suggests the presence of inter-residue H-bonding between O3HGlc and O5Gal. Quantitative analysis of 3JHCOH and 3JCCOH values in 20 indicates that approximately 85% of the forms in solution have geometries consistent with H-bonding. These results suggest that H-bonding between adjacent and/or remote residues may play a role in dictating preferred glycosidic bond conformation in simple and complex oligosaccharides in aqueous solution.

Combined NMR three‐bond scalar coupling measurements and QM calculations to calculate OH‐rotamer equilibrium of polyalcohols

“…These scalar couplings were determined using standard basis set [B3LYP/6-31111G(d,p)] as well as using tight ''s'' functions (suggested basis set: aug-cc-pvdz 44 ) for accurate description of FC contribution as implemented in Gaussian 03 rev/D. 34,44 The dependence of the obtained coupling constants on tor2 is in good consistence with the previously obtained results, 9 where hypersurfaces of such functional relationships were determined for similar compounds.…”

“…Recent theoretical approaches based on density functional theory (DFT) take all these factors into consideration and report new Karplus equations for 3 J H,OH and 3 J C,OH couplings, which account for both the nature and orientation of the prevailing internal and terminal electronegative substituents. 9 The above described limited but significant experimental uncertainties as well as the explicit knowledge of both the geometrical and stability properties of the above polyalcohol models initiated the detailed QM analysis described below.…”

“…Because stereoselective synthesis of such compounds sometimes requires special steric orientation of functional groups, there is a general interest in describing the solution state conformers of vicinal polyalcohols and saccharides. [6][7][8][9] However, it is well known that by recruiting only protons of CÀ ÀH bonds for the description of topology will not eliminate ambiguities due to the presence of the flexible hydroxyl groups (Schemes 1 and 2). An aliphatic vicinal polyalcohol contains at least two unconstrained torsional angles per À ÀCHOH subunit (Scheme 1A), namely those of C i22 -C i21 -C i -C i11 and C i21 -C i -ith and the adjacent carbon atoms as well as v(C i21 -C i -O i -H i ) denoting the orientation of the OH-group attached to the ith carbon atom for subunit C i HÀ ÀOH.…”

“…Although hydroxyl exchange rates can be slowed by supercooling the aqueous solution, 17 or by using organic solvents (DMSO-d 6 , acetone-d 6 , CDCl 3 ) 18 or cosolvents, 19 making the measurement of the conformationally relevant three-bond couplings 20 feasible, however, till the recent year, 9 appropriate Karplus equation relating the heteronuclear vicinal coupling constant 3 J C,OH to CÀ ÀO torsion angle has not been available. Although there are other NMR probes to study the involvement of OH groups in hydrogen bonds, such as determining the temperature and/or solvent dependence of OH-chemical shifts [21][22][23][24][25][26][27][28][29] or measuring the isotope effects.…”

An NMR investigation of putative interresidue H-bonding in methyl α-cellobioside in solution

“…[1][2][3][4][5][6] In recent years, considerable effort has been directed towards improving these determinations partly through the development of more quantitative analyses of NMR spin-spin coupling constants (J-couplings) involving 13 C and 1 H, which are abundant in saccharides. For example, homonuclear 13 C-13 C spin-couplings provide unique and useful constraints not only to assess O-glycosidic linkage geometry 7,8 but also to establish aldohexopyranosyl ring conformation (e.g., 3 J C1,C6 and 3 J C3,C6 values in aldohexopyranosyl rings).…”