image:
(A) Non-Covalent Interaction (NCI) analysis of NDI-COE. Blue indicates hydrogen bond, green indicates van der Waals (vdW)
interaction, and red indicates steric repulsion, respectively. (B) Bond length and binding site between NDI-COE and water. (C) Calculated Raman spectral comparison of NDI-COE in the presence of water. (D) NCI analysis of Ben-COE. (E) Bond length and binding site between Ben-COE and water. (F) Calculated Raman spectral comparison of Ben-COE in the presence of water. Energy level diagram and photophysical processes of (G) Ben-COE and (H) NDI-COE. In 3G, S0 : neutral molecule in the singlet ground state D0 : ground state doublet of the anion formed after accepting one electron. AEA: adiabatic electron affinity. (I) Ground state and excited state redox potentials (V vs NHE) were calculated by DFT using the polarizable continuum model (PCM) with water as a solvent. (J) Ground state and excited state redox potentials (Eₒₓ, Eᵣₑd, Eₒₓ*, Eᵣₑd*; V vs NHE) and Frontier orbital energies (HOMO, LUMO; eV) of NDI-COE and Ben-COE, calculated by DFT using PCM with water as a solvent.
Credit: J. Am. Chem. Soc. 2026, 148, 5, 5419–5435
A research team led by Professor Jin Yong Lee from the Department of Chemistry of Sungkyunkwan University (Co-first author: HyoungChul Ham), in collaboration with research teams from Korea University and the National University of Singapore, has developed a next-generation phototherapeutic agent, ‘NDI-COE’. This agent induces pyroptosis (inflammatory cell death) in hypoxic tumor tissues by directly oxidizing intracellular water. Designed to overcome the oxygen-dependency limits of conventional photodynamic therapy by intercalating into the cell membrane to oxidize water, this research was published in the Journal of the American Chemical Society (IF: 15.7) on January 28, 2026
Notably, Professor Lee’s team elucidated the superior photochemical mechanism of NDI-COE at the molecular level based on Density Functional Theory (DFT) calculations. Non-covalent interaction (NCI) analysis revealed that NDI-COE forms double hydrogen bonds with water molecules, stably trapping them with a much stronger binding energy (-5.21 kcal/mol) compared to the control group. Furthermore, electronic structure analysis demonstrated that the spin-orbit coupling (SOC) efficiency for the transition to the highly reactive triplet state (T1) upon light irradiation was approximately 7.5 times higher (2.87 cm-1) than the control, proving its outstanding photochemical reactivity. Moreover, redox potential calculations verified that the excited-state oxidation potential of NDI-COE (-0.39 V) provides the thermodynamic conditions to promote spontaneous electron transfer to oxygen molecules, thereby generating reactive oxygen species highly efficiently.
The properties of this novel material, quantitatively characterized through these DFT calculations, are expected to serve as a crucial theoretical foundation for designing innovative and precise next-generation phototherapeutics capable of overcoming hypoxic tumor environments.
Journal
Journal of the American Chemical Society
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