Development of a Conformational Sampling Method for Transition State Structures With Diverse Active Bond Lengths

ABSTRACT

We describe TStrail, a transition state (TS) conformational sampling tool that automatically generates TS conformers without fixing the bond forming/breaking distance of an initial TS structure. Conventionally, the conformations of TS structures were searched with the fixed length of active bonds, making it easier to re‐optimize to the TS but potentially limiting the comprehensiveness of TS conformers when the active bond lengths varied among conformers. By collectively performing pathway searches among various reactant conformations, TStrail was able to generate TS conformers with different active bond lengths. Furthermore, applications to more complex systems demonstrated that TStrail provides a practical tool for systematically analyzing challenging TS conformers, particularly for large, flexible, ionic, and structurally complex TSs, thereby enabling deeper mechanistic insights through the identification of diverse TS conformers and reaction pathways.