biostudies-literatureUnknownWei SPrecise design of excited-state intramolecular proton transfer (ESIPT) molecules targeting advanced optoelectronic or biological sensing applications presents a fundamental challenge. Controlling the energy difference (Δ<i>E</i>*) between normal (N*) and tautomeric (T*) excited-state forms is crucial, yet the complex interplay of hydrogen bond (H-bond) strength, proton donor acidity, and proton acceptor basicity with Δ<i>E</i>* remains insufficiently explored. Conventional trial-and-error approaches for designing tailored ESIPT compounds suffer from inefficient synthesis. To address this, we constructed a high-quality ESIPT dataset by introducing ten substituents with progressively increasing electron-donating capacity into six representative ESIPT parent scaffolds. Integrating qualitativeChemical sciencehttps://www.ebi.ac.uk/biostudies/studies/S-EPMC12910287biostudies-literatureUnveiling key descriptors &lt;i&gt;via&lt;/i&gt; machine learning: toward rational molecular design of chromophores with excited-state intramolecular proton transfer.PMC12910287Yang ZLi YGuo YWei SXia AYang CKuang ZZhao HfalseUnveiling key descriptors &lt;i&gt;via&lt;/i&gt; machine learning: toward rational molecular design of chromophores with excited-state intramolecular proton transfer.Precise design of excited-state intramolecular proton transfer (ESIPT) molecules targeting advanced optoelectronic or biological sensing applications presents a fundamental challenge. Controlling the energy difference (Δ<i>E</i>*) between normal (N*) and tautomeric (T*) excited-state forms is crucial, yet the complex interplay of hydrogen bond (H-bond) strength, proton donor acidity, and proton acceptor basicity with Δ<i>E</i>* remains insufficiently explored. Conventional trial-and-error approaches for designing tailored ESIPT compounds suffer from inefficient synthesis. To address this, we constructed a high-quality ESIPT dataset by introducing ten substituents with progressively increasing electron-donating capacity into six representative ESIPT parent scaffolds. Integrating qualitative2026-01-01T00:00:00Z2026 Feb2026-07-16T11:56:54.242Z2026-07-09T10:53:01.139ZS-EPMC129102874171020810.1039/d5sc07051a