Mechanistic Insights into Photo-Induced Bond Dissociation of a 2-(4-Nitrophenyl)-1H-indole-3-ylmethyl (NPIM) Derivative: A Case Study on Quantum Spin-Manipulation for Uncaging.
- 1The Institute for Solid State Physics, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba277-8581, Japan.
- 2Department of Chemistry, Graduate School of Advanced Science and Engineering, Hiroshima University, Higashi-Hiroshima, Hiroshima739-8526, Japan.
- 3Hiroshima Research Center for Photo-Drug-Delivery Systems (Hi-P-DDS), Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima739-8526, Japan.
Abstract
Photolabile protecting groups (PPGs) are indispensable tools for spatiotemporally controlled release of reactive functional groups. Recently, we proposed a quantum spin-manipulation (QSM-1) strategy that employs triplet ground-state cations to render ion-pair recombination spin-forbidden, thereby enhancing the uncaging quantum yield. In this study, the photodissociation mechanism of a 2-(4-nitrophenyl)-1H-indole-3-ylmethyl (NPIM) photocage bearing a benzoate leaving group was investigated to evaluate the effectiveness of a triplet excited-state-mediated QSM pathway (QSM-2). Spectroscopic analyses revealed that the excited state of NPIM possesses a relatively small singlet-triplet energy gap (ΔEST = 5.3 kcal mol-1), enabling efficient intersystem crossing (ISC) from the intramolecular charge-transfer singlet excited state to the triplet excited state. Oxygen-quenching experiments demonstrated that photodissociation proceeds predominantly from the triplet excited state. Time-resolved absorption spectroscopy identified the singlet excited state (τ = 1.6 ns), triplet excited state (τ = 2.3 μs), and NPIM radical intermediate (τ = 1.5 ms). In situ infrared analysis directly detected benzoic acid, an oxidized NPIM product, and CO2 generated from the benzoyl radical, supporting a homolytic bond-cleavage mechanism. Ultrafast time-resolved infrared spectroscopy of the NPIM chromophore revealed formation of a twisted intramolecular charge-transfer state that promotes ISC by reducing ΔEST. Density functional theory calculations further indicate that C-O bond homolysis from the triplet excited state is energetically feasible and is driven by relief of excited-state antiaromaticity. These results establish that uncaging of NPIM derivatives proceeds through triplet-state homolysis and demonstrate the validity of the QSM-2 strategy for designing efficient photochemical release systems.
Related
- Computational Insights into Mechanostability and Dissociation Dynamics of the Dengue Virus Envelope Protein Ectodomain Dimer Across pH and Temperature Gradients
- Overlooked Roles of Oxygen in PFAS Degradation by UV/Sulfite: Mechanistic Insights and Engineering Implications
- Light Magnesium Oxide Nanosheets for Efficient Fluoride Removal from Geothermal Water: Rapid Adsorption and Mechanistic Insights
- Utilizing Electrosorption for Efficient Removal of Polyethylene Microplastics from Water: Critical Factors and Mechanistic Insights
- Mechanistic Insights into Polyphenol Oxidase Inhibition by Four Bioactive Constituents from Hydrangea macrophylla Serrata: Antioxidant Activity of Single Compounds Compared to the Whole-Leaf Extract
BibTeX
@article{kuroishi2026mechanistic,
title = {{Mechanistic Insights into Photo-Induced Bond Dissociation of a 2-(4-Nitrophenyl)-1H-indole-3-ylmethyl (NPIM) Derivative: A Case Study on Quantum Spin-Manipulation for Uncaging.}},
author = {Kenta Kuroishi and Ryuei Hayashi and Ryoko Oyama and Shunsuke Tanaka and Kotaro Ogawa and Yuta Murotani and Ryusuke Matsunaga and Jun Yoshinobu and Manabu Abe},
journal = {Journal of the American Chemical Society},
year = {2026},
month = sep,
doi = {10.1021/jacs.6c13942},
url = {https://europepmc.org/article/MED/42915514},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Mechanistic Insights into Photo-Induced Bond Dissociation of a 2-(4-Nitrophenyl)-1H-indole-3-ylmethyl (NPIM) Derivative: A Case Study on Quantum Spin-Manipulation for Uncaging.
AU - Kenta Kuroishi
AU - Ryuei Hayashi
AU - Ryoko Oyama
AU - Shunsuke Tanaka
AU - Kotaro Ogawa
AU - Yuta Murotani
AU - Ryusuke Matsunaga
AU - Jun Yoshinobu
AU - Manabu Abe
PY - 2026
DA - 2026/09/01
JO - Journal of the American Chemical Society
DO - 10.1021/jacs.6c13942
UR - https://europepmc.org/article/MED/42915514
AB - Photolabile protecting groups (PPGs) are indispensable tools for spatiotemporally controlled release of reactive functional groups. Recently, we proposed a quantum spin-manipulation (QSM-1) strategy that employs triplet ground-state cations to render ion-pair recombination spin-forbidden, thereby enhancing the uncaging quantum yield. In this study, the photodissociation mechanism of a 2-(4-nitrophenyl)-1H-indole-3-ylmethyl (NPIM) photocage bearing a benzoate leaving group was investigated to evaluate the effectiveness of a triplet excited-state-mediated QSM pathway (QSM-2). Spectroscopic analyses revealed that the excited state of NPIM possesses a relatively small singlet-triplet energy gap (ΔEST = 5.3 kcal mol-1), enabling efficient intersystem crossing (ISC) from the intramolecular charge-transfer singlet excited state to the triplet excited state. Oxygen-quenching experiments demonstrated that photodissociation proceeds predominantly from the triplet excited state. Time-resolved absorption spectroscopy identified the singlet excited state (τ = 1.6 ns), triplet excited state (τ = 2.3 μs), and NPIM radical intermediate (τ = 1.5 ms). In situ infrared analysis directly detected benzoic acid, an oxidized NPIM product, and CO2 generated from the benzoyl radical, supporting a homolytic bond-cleavage mechanism. Ultrafast time-resolved infrared spectroscopy of the NPIM chromophore revealed formation of a twisted intramolecular charge-transfer state that promotes ISC by reducing ΔEST. Density functional theory calculations further indicate that C-O bond homolysis from the triplet excited state is energetically feasible and is driven by relief of excited-state antiaromaticity. These results establish that uncaging of NPIM derivatives proceeds through triplet-state homolysis and demonstrate the validity of the QSM-2 strategy for designing efficient photochemical release systems.
SN - 0002-7863
SN - 1520-5126
ER -