Anomeric effect computer modeling

The measures of the anomeric effect, based on Eqs. 7-i are of relative character, because they are expressed in reference to a standard compound or a computational method. Some absolute measure is needed for theoretical considerations, and it could be simply the positive difference of the energy of the a and e isomers or of the sc and ap conformation in model compounds. ... 

A significant contribution in this area was presented by Cuevas from his theoretical analysis of the anomeric effect in S—C—P units. Thus, using computational resources and 2-dimethylphosphinoyl-l,3-dithiane as a model system the author argues that the polar nature of the P—O bond... 

Additional relevant work was presented in 2007 by Takahashi et al. using computational methods in the modeling of substituted oxanes and 1,3-dioxanes. These researchers found that the interatomic distances between axial H4 and axial H6 and the anomeric substituent (OMe, F, Cl, Br) are shorter than the sum of their van der Waals radii, which suggests that the magnitude of the anomeric effect in these heterocycles is due in part to the stabilization provided by C—H—Y hydrogen bonding (Scheme 9) (07CAR1202). 

To reproduce an exo-anomeric effect, separate energy functions, Eqs. [3] and [4], were incorporated for a- and p-anomers. The parameters for these equations were derived by fitting to the rotational energy curves for dimethox-ymethane computed with nonoptimized geometries at the HF/4-31G ab initio level.Dimethoxymethane is the simplest chemical model system for a gly-cosidic linkage. 

To conclude on a personal note, I first encountered the JP R paper several years ago when I became interested in the characterization of solvation effects on various anomeric equilibria in pyranosides [24, 25]. It goes without saying that phenomenal advances in computational power now permit us to address considerably larger model systems than those accessible to JP R and moreover to do so at much more refined levels of electronic structure theory [26-28]. Nevertheless, subsequent work has been guided by JP R s seminal 1972 contribution, which convincingly elucidated the key physical underpinnings of the anomeric effect, successfully predicted the most important qualitative consequences, and set the foundation stone for future quantum chemical conformational analysis of sugars. 

Computation of the conformational energies of 2-methoxytetrahydropyran, a model for the methyl aldopyranosides, gave results in agreement with experimental observations. A preference for the axial conformer was apparent, but the nature of the stabilizing factor (anomeric effect) was not resolved. Force-field calculations have been extended to include alcohols, ethers, simple acetals, and 2-methoxytetrahydropyran. 2 The preference of 2-methoxytetrahydropyran for the axial conformer was attributed to interaction of the axial lone-pair orbital on the ring-oxygen atom with the axial C—O bond of the methoxy-group, which can be represented by the resonance structure (501) (see also, Vol. 6, p. 163). 

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