The reverse reaction is equally complex but for different reasons. The deep and narrow ring state exhibits low anharmonicity, making it difficult to determine the correct biasing direction without mistakenly exploring alternative anharmonic channels, potentially leading to undesired C -C or C -H rearrangements. Despite these challenges, the method effectively identifies the ring-opening pathway and smoothly guides the system out of the metastable state, as depicted in the lower right panel of Figure .2.