Aromaticity recovery as a driving force for electron transfer and radical addition in 5-hydroxy-1,4-naphthoquinone derivatives.

This study introduces the concept of aromaticity recovery as a unified framework to rationalize electron transfer and radical reactivity in 5-hydroxy-1,4-naphthoquinone (HXNQ) derivatives. Density functional theory (M06-2X/6-311++G(d,p), SMD) was employed to investigate hydroxyl radical (HO˙) scavenging via electron transfer (ET), radical adduct formation (RAF), and hydrogen atom transfer (HAT) pathways. The results show that electron addition or radical attack promotes a more delocalized and partially aromatized electronic structure, providing an electronic driving force for the observed reactivity. Environmental polarity significantly stabilizes ionic intermediates, thereby favoring ET processes. Among the pathways examined, RAF at the C2[double bond, length as m-dash]C3 bond is both kinetically and thermodynamically preferred, exhibiting near-barrierless activation and strong exothermicity. In contrast, HAT is hindered by a stabilizing intramolecular hydrogen bond that imposes conformational constraints. Aromaticity analyses based on HOMA and NICS descriptors, supported by MEP, HOMO-LUMO, and ELF calculations, reveal that the radical anion (HHNQ˙-) represents a unique electronic state in which partial aromaticity recovery occurs within the quinoid ring while the aromatic character of the benzenoid ring is largely preserved. This dual stabilization provides a structural basis for the favorable ET and RAF pathways. These findings establish aromaticity recovery as a useful framework for understanding and predicting radical-scavenging behavior in quinone systems.