The Cooperative Double Helicenyl Fragment Model: Efficiently Predicting Stereochemical Stability of...

Predicting the stereochemical stability of complex multiple helicenes (MHs) is conventionally hindered by the combinatorial explosion of stereoisomers and the prohibitive O(N⁴) computational scaling of density functional theory (DFT). Herein, we introduce the cooperative double helicenyl fragment (CDHF) model, which deconstructs global relative enthalpies into additive local enthalpic contributions to overcome these limitations. Rigorously validated across seven experimentally synthesized MHs, the CDHF model consistently reproduces the energy distribution of expansive stereoisomeric spaces and correctly pinpoints the experimentally isolated global minima. Exploiting its exceptional parameter transferability, the model functions as a modular design toolkit. We demonstrated this utility by rationally engineering a hypothetical pentadecapole helicene encompassing 10,944 stereoisomers. By strategically manipulating local topologies, we shifted its global minimum to a highly symmetric C₃ configuration, achieving a computational speedup of approximately 3 × 10⁵ over full-molecule DFT. Photophysically, this symmetry-driven architecture effectively eliminates the internal dichroic cancellation, enhancing the long-wavelength chiroptical purity by 82%. Ultimately, the CDHF model provides a precise thermodynamic blueprint for rationally designing complex chiral architectures, establishing itself as a powerful presynthetic strategy for developing advanced chiroptical materials.