Anomeric effect parameterization

Although the treatment of stereoelectronic effects is somewhat beyond the traditional capabilities of molecular mechanics, force fields can be suitably parameterized to reproduce their energetic and structural manifestations. In the following, we discuss the parameterization of MM2-80 and MM2-87 for the anomeric effect characteristic of the N—C—N moiety22. 

Carbohydrates have been included in the wide range of molecules used in the parameterization of MM2 and of MM3. Alcohol and ether parameters have usually been determined from simple alcohols and ethers themselves. However, carbohydrates contain some unusual features in the acetal linkages, and in the many vicinal hydrogen-bonded hydroxyl groups. The "anomeric effect", first discovered by Edward (15) and popularized by Lemieux (16.), is best known in carbohydrates, although, of course, it occurs in other classes of compounds as well. One apparent result of this effect is that an axial alkoxy substituent is often more stable than the corresponding equatorial substituent when attached at the Cl position of a tetrahydropyranyl ring. This effect can be... 

Another anomeric effect is that acetal C-0 bonds, and to a lesser extent, the bonds between acetal carbons and ether oxygens, are shortened or elongated as a function of their associated torsional angles. Jeffrey and Taylor modified MMl to account for these anomeric effects (17) and similar additions were put in the standard 1985 version of MM2 (11). The parameterization of MM3 for anomeric effects is preliminary, with recent (18-20) results being monitored. 

MM2 has been parameterized for a wide range of molecules, including those exhibiting the anomeric effect. The details of the MM2 and MM3 force fields and their application to carbohydrates have been discussed elsewhere. Of particular relevance to carbohydrates is the ability of these force fields to predict the subtle variations in the Cano C) bond lengths that relate to the anomeric effect. In order to account correctly for the observed relationship between glyco-sidic torsion angle and Cano-O bond lengths, MM2 and MM3 employ a torsion-stretch cross term (equations 21 and 22). 

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