PCILO quantum-mechanical relaxed conformational energy map of methyl 4-thio-alpha-maltoside in solution

A theoretical study is presented of the conformational properties of methyl 4-thio-alpha-maltoside. Quantum-chemical PCILO (perturbed configuration interaction with localized orbitals) energy minimization with evaluation of the solvent effect has been used to calculate semi-rigid and relaxed (phi, psi) conformational-energy surfaces in 1,4-dioxane, methanol, dimethyl sulfoxide, and water. The inclusion of molecular flexibility in the conformational analysis of this disaccharide derivative was found to have a significant effect upon the allowed conformational space of the molecule. Calculations revealed the existence of 15 stable conformers having different internal geometries. The relative abundance of these conformers is strongly influenced by solvent. The locations of the global minima and "virtual" conformations vary with solvent and the flexibility of methyl 4-thio-alpha-maltoside significantly decreases from 1,4-dioxane to water. It was found that the conformational properties of methyl 4-thio-alpha-maltoside differ from those of the corresponding 4-oxygenated analogue, methyl alpha-maltoside. The calculated solution behaviour is supported by very good agreement between the theoretical values mean value of 3JC-4,H-1' = 2.67 and mean value of 3JC-1',H-4 = 5.24 Hz calculated as ensemble averages over all conformers on the relaxed map and the experimental values of 2.95 and 5.15 Hz in water solution.