Hierarchical approach to conformational search and selection of computational method in modeling the mechanism of...

We describe automated procedures for the first stages of a systematic computational investigation of reaction mechanisms. They include (i) selection of computational method and basis set based on statistical analysis of structural and energy data relating to experimental values, (ii) determination of all distinct conformations of transition states with large conformational freedom, and (iii) generation of unknown geometry of the transition states, based on pre-defined connectivity of the atoms involved in the reaction. For the conformational search we employed an efficient procedure for exploration of various possible conformations of the transition states and elimination of the equivalent structures in several steps using molecular-mechanical and quantum-mechanical methods. The procedure was applied to the determination of the structures of transition states and intermediates in the ammonolysis of monoformylated 1,2-ethanediol, which were subsequently used for identification of the lowest energy reaction paths. For the same reaction system we also used the approach for generation of the initial structures of transition states with unknown geometry. The reported procedures are implemented in the MolRan program suite.