Tautomeric Diversity in the Baicalein Radical Cation: EPR Fingerprints of a Traditional Chinese Medicine Antioxidant
- 1Theoretical Chemistry, Heidelberg University, Im Neuenheimer Feld 229, Heidelberg, Germany, D-69120
Abstract
The radical cation of baicalein, the principal bioactive flavonoid of the Traditional Chinese Medicine herb Scutellaria baicalensis, has been predicted to undergo an intramolecular proton transfer from the 5-hydroxyl to the 4carbonyl oxygen. This tautomerization produces two distinct electronic configurations, denoted C1 (canonical) and C2 (proton-transferred), whose relative populations and reactivities may determine the antioxidant behavior of the molecule within the single-electron-transfer–proton-transfer (SET-PT) pathway. The two tautomers have not, however, been distinguished experimentally; their UV-Vis signatures differ only subtly. Here we report the first EPR hyperfine fingerprints of the two tautomers, computed at the DFT/UM06-2X/EPR-III level across fourteen media. Three qualitatively distinct signatures separate C1 from C2 (values in water): a near-doubling of the isotropic coupling at the 5-hydroxyl oxygen O5 (from −5.88 to −11.77 G), a sign reversal at the aromatic carbon C5 (from +4.83 to −5.77 G), and the disappearance of the mobile proton’s coupling (from −3.49 to +0.30 G). All three qualitative signatures are preserved across dielectric constants from 1 to 78, making them robust diagnostics of the tautomeric state in a wide range of environments. Because EPR hyperfine couplings report directly on spin density rather than on electronic transitions, they provide an unambiguous experimental handle for detecting the tautomeric diversity of the baicalein radical cation.
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BibTeX
@misc{baldea2026tautomeric,
title = {{Tautomeric Diversity in the Baicalein Radical Cation: EPR Fingerprints of a Traditional Chinese Medicine Antioxidant}},
author = {Ioan Bâldea and Ioan Baldea},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15009667/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009667/v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Tautomeric Diversity in the Baicalein Radical Cation: EPR Fingerprints of a Traditional Chinese Medicine Antioxidant
AU - Ioan Bâldea
AU - Ioan Baldea
PY - 2026
DA - 2026/09/29
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009667/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009667/v1
AB - The radical cation of baicalein, the principal bioactive flavonoid of the Traditional Chinese Medicine herb Scutellaria baicalensis, has been predicted to undergo an intramolecular proton transfer from the 5-hydroxyl to the 4carbonyl oxygen. This tautomerization produces two distinct electronic configurations, denoted C1 (canonical) and C2 (proton-transferred), whose relative populations and reactivities may determine the antioxidant behavior of the molecule within the single-electron-transfer–proton-transfer (SET-PT) pathway. The two tautomers have not, however, been distinguished experimentally; their UV-Vis signatures differ only subtly. Here we report the first EPR hyperfine fingerprints of the two tautomers, computed at the DFT/UM06-2X/EPR-III level across fourteen media. Three qualitatively distinct signatures separate C1 from C2 (values in water): a near-doubling of the isotropic coupling at the 5-hydroxyl oxygen O5 (from −5.88 to −11.77 G), a sign reversal at the aromatic carbon C5 (from +4.83 to −5.77 G), and the disappearance of the mobile proton’s coupling (from −3.49 to +0.30 G). All three qualitative signatures are preserved across dielectric constants from 1 to 78, making them robust diagnostics of the tautomeric state in a wide range of environments. Because EPR hyperfine couplings report directly on spin density rather than on electronic transitions, they provide an unambiguous experimental handle for detecting the tautomeric diversity of the baicalein radical cation.
ER -