AB-INITIO STUDIES OF LIPID MODEL SPECIES .2. CONFORMATIONAL-ANALYSIS OF INOSITOLS

Molecular species containing inositol are among the most ubiquitous na turally occurring compounds. For example they are commonly found in bi omembranes as one of the few head groups of phospholipids. To help cha racterize their structural properties we have studied the conformation al preferences of inositol. It has long been held that among the eight possible cis-trans isomers of inositols shown in Figure 1, the all-eq uatorial (6e) scyllo-inositol is intrinsically the most stable. Howeve r we report here ab initio calculations using Hartree-Fock and second- order Moller-Plesset perturbation methods and also calculations based on density-functional methods, all of which show that this long held v iew on conformational analysis of isolated inositol molecules is quest ionable. We have found that the naturally much more abundant myo-inosi tol, with five equatorial and one axial hydroxyl groups (5e/1a), and t he nonnaturally occurring neo-inositol with four equatorial and two ax ial hydroxyls (4e/2a), tend to be slightly lower in energy than scyllo -inositol. In terms of the free energy, contributions from nuclear mot ions also favor myo-inositol over scyllo-inositol, making the former c onsistently more stable. Although an axial hydroxyl group introduces s train energy primarily due to 1,4 O-axial...O and O-axial...C repulsio ns, it can form more favorable intramolecular hydrogen bonds, which ap pear to be dominant. The O-axial...H-axial...C interaction also favors the axial hydroxyl orientation. On the other hand, when all intramole cular hydrogen bonds in scyllo- and myo-inositols are removed by prope rly orienting OH groups, as may occur in aqueous solution or crystals, scyllo becomes lower in energy than myo. Calculations were also carri ed out on phosphoryl inositols, and the results indicate that axial ph osphate substitution may be favored as well. These effects were analyz ed in terms of the cyclohexane ring structures and compared with exper imental results.