Interpretable Artificial Intelligence Decodes the Chemical Structural Essence of Twisted Intramolecular Charge...

D-π-A-type fluorescent materials are crucial tools in life sciences and medicine, with their development hinging on a precise understanding of fluorophore mechanisms, particularly twisted intramolecular charge transfer (TICT) and planar intramolecular charge transfer (PICT) processes. These fluorophores exhibit unique charge transfer properties, making them highly valuable in organic optoelectronics, fluorescent probes, and sensors. However, despite their growing applications, the structural essence of TICT and PICT fluorophores remains poorly understood. This often results in molecules with similar structures displaying charge transfer modes that contradict design expectations, substantially hindering the application of TICT and PICT fluorescent probes. In this study, we meticulously designed various computational strategies based on interpretable machine learning to thoroughly deconstruct the chemical structural essence of TICT and PICT fluorophores. Utilizing the first real-world TICT and PICT dataset, we constructed predictive models that balance both interpretability and accuracy (area under the receiver operating characteristic curve = 0.846) using a range of algorithms, including deep learning. We established artificial intelligence (AI)-guided rules comprising 5 structural factors-electron-donating group strength, electron-withdrawing group strength, alkyl cyclization, steric hindrance, and solvent-solute interactions-that influence TICT and PICT. These rules provide obvious guidance for probe design based on molecular rigidity and charge transfer driving forces. Compared to community-suggested rules, the AI-guided rules achieved an over 20% improvement in accuracy in a controlled evaluation. By applying these rules, we successfully synthesized and validated several representative fluorophores that are challenging to distinguish using chemical intuition alone. Both quantitative calculations and experimental results confirmed the accuracy of the model and the practicality of the AI-guided rules. This novel approach is expected to establish a novel paradigm for exploring ideal TICT and PICT molecules, offering a robust framework for future research and application in fluorescent materials.