Anion and neutral-state bioluminescence reactions induced by imidazopyridine oxidation: Both identified as charge-transfer-induced luminescence (CTIL) from a density functional theory perspective.
Fuente:
PubMed
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Artículo científico |
| Language: | en |
| Published: |
Journal of photochemistry and photobiology. B, Biology
2026
|
| Subjects: | |
| Online Access: | |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1868266044103065600 |
|---|---|
| author | Wu, Nan Xin, Yong-Xuan Xu, Zhi-Chao Bai, Yan-Hong |
| author_facet | Wu, Nan Xin, Yong-Xuan Xu, Zhi-Chao Bai, Yan-Hong Wu, Nan Xin, Yong-Xuan Xu, Zhi-Chao Bai, Yan-Hong |
| collection | PubMed - marine biology |
| contents | Anion and neutral-state bioluminescence reactions induced by imidazopyridine oxidation: Both identified as charge-transfer-induced luminescence (CTIL) from a density functional theory perspective. Wu, Nan Xin, Yong-Xuan Xu, Zhi-Chao Bai, Yan-Hong Imidazoles Oxidation-Reduction Pyridines Density Functional Theory Luminescence Anions Luminescent Measurements Pyrazines Heterocyclic Compounds, 1-Ring Bioluminescence, generated through the luciferase-catalyzed oxidation of luciferin, produces visible light and is widely used in biomedical imaging and related fields. Imidazopyridine (ImPy) constitutes the core luminescent scaffold of coelenterazine-type fluorophores, and its oxidation yields an anionic dioxetanone intermediate that typically undergoes cleavage. This process generally involves charge transfer between substituents and the formation of radical electrons, a phenomenon known as charge-transfer-induced luminescence (CTIL). The anionic dioxetanone can also be converted to its neutral form through protonation or intramolecular bonding. Although neutral dioxetanone can likewise undergo cleavage accompanied by charge transfer between substituents, the transferred charge is small. It has therefore often been overlooked, leading to the prevailing assumption that neutral-state cleavage does not belong to the CTIL category. The mechanistic distinction between these two cleavage modes remains unresolved. In this work, an ImPy model was constructed based on the structures of coelenterazine and furimazine, two representative marine luciferins. Using density functional theory (DFT), we computed the oxidation pathway leading to dioxetanone formation and examined its cleavage under various anionic and neutral states. Charge-transfer behavior and reaction barriers were evaluated, and wavefunction analyses were performed to visualize the evolution of radical-electron distribution and atomic interactions throughout the reaction. Our results show that although the amount of charge transferred between substituents in the neutral state is small, it remains essential, as these subtle charge shifts initiate dioxetanone cleavage. Neutral-state cleavage should therefore be classified as part of the CTIL mechanism, consistent with the anionic case. In both neutral and anionic states, the reaction is triggered by the transfer of negative charge to the central CCOO four-membered ring, and this transferred charge induces dissociation of the two oxygens, thereby initiating dioxetanone cleavage. In the anionic state, the pyrazinamine (PMN) moiety, which carries a substantial negative charge adjacent to CCOO, acts as the donor. The donated charge initially drives the separation of the two oxygen atoms within CCOO, subsequently propagates through the dioxetanone framework, induces cleavage of the C-C bond, and ultimately results in dioxetanone dissociation. In the neutral state, the only available donor is a single carbonyl oxygen atom, and the donated negative charge is sufficient only to separate the two oxygen atoms but insufficient to cleave the C-C bond of the CCOO ring. Additional energy is therefore required to amplify charge transfer and achieve full C-C bond rupture. By varying the initial negative charge load on the donor moiety, we further identified that a higher negative charge facilitates transfer to CCOO and thereby lowers the reaction barrier. |
| format | Artículo científico |
| id | pubmed_42184468 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | Journal of photochemistry and photobiology. B, Biology |
| record_format | pubmed |
| spellingShingle | Anion and neutral-state bioluminescence reactions induced by imidazopyridine oxidation: Both identified as charge-transfer-induced luminescence (CTIL) from a density functional theory perspective. Wu, Nan Xin, Yong-Xuan Xu, Zhi-Chao Bai, Yan-Hong Imidazoles Oxidation-Reduction Pyridines Density Functional Theory Luminescence Anions Luminescent Measurements Pyrazines Heterocyclic Compounds, 1-Ring Anion and neutral-state bioluminescence reactions induced by imidazopyridine oxidation: Both identified as charge-transfer-induced luminescence (CTIL) from a density functional theory perspective. Wu, Nan Xin, Yong-Xuan Xu, Zhi-Chao Bai, Yan-Hong Imidazoles Oxidation-Reduction Pyridines Density Functional Theory Luminescence Anions Luminescent Measurements Pyrazines Heterocyclic Compounds, 1-Ring Bioluminescence, generated through the luciferase-catalyzed oxidation of luciferin, produces visible light and is widely used in biomedical imaging and related fields. Imidazopyridine (ImPy) constitutes the core luminescent scaffold of coelenterazine-type fluorophores, and its oxidation yields an anionic dioxetanone intermediate that typically undergoes cleavage. This process generally involves charge transfer between substituents and the formation of radical electrons, a phenomenon known as charge-transfer-induced luminescence (CTIL). The anionic dioxetanone can also be converted to its neutral form through protonation or intramolecular bonding. Although neutral dioxetanone can likewise undergo cleavage accompanied by charge transfer between substituents, the transferred charge is small. It has therefore often been overlooked, leading to the prevailing assumption that neutral-state cleavage does not belong to the CTIL category. The mechanistic distinction between these two cleavage modes remains unresolved. In this work, an ImPy model was constructed based on the structures of coelenterazine and furimazine, two representative marine luciferins. Using density functional theory (DFT), we computed the oxidation pathway leading to dioxetanone formation and examined its cleavage under various anionic and neutral states. Charge-transfer behavior and reaction barriers were evaluated, and wavefunction analyses were performed to visualize the evolution of radical-electron distribution and atomic interactions throughout the reaction. Our results show that although the amount of charge transferred between substituents in the neutral state is small, it remains essential, as these subtle charge shifts initiate dioxetanone cleavage. Neutral-state cleavage should therefore be classified as part of the CTIL mechanism, consistent with the anionic case. In both neutral and anionic states, the reaction is triggered by the transfer of negative charge to the central CCOO four-membered ring, and this transferred charge induces dissociation of the two oxygens, thereby initiating dioxetanone cleavage. In the anionic state, the pyrazinamine (PMN) moiety, which carries a substantial negative charge adjacent to CCOO, acts as the donor. The donated charge initially drives the separation of the two oxygen atoms within CCOO, subsequently propagates through the dioxetanone framework, induces cleavage of the C-C bond, and ultimately results in dioxetanone dissociation. In the neutral state, the only available donor is a single carbonyl oxygen atom, and the donated negative charge is sufficient only to separate the two oxygen atoms but insufficient to cleave the C-C bond of the CCOO ring. Additional energy is therefore required to amplify charge transfer and achieve full C-C bond rupture. By varying the initial negative charge load on the donor moiety, we further identified that a higher negative charge facilitates transfer to CCOO and thereby lowers the reaction barrier. |
| title | Anion and neutral-state bioluminescence reactions induced by imidazopyridine oxidation: Both identified as charge-transfer-induced luminescence (CTIL) from a density functional theory perspective. |
| topic | Imidazoles Oxidation-Reduction Pyridines Density Functional Theory Luminescence Anions Luminescent Measurements Pyrazines Heterocyclic Compounds, 1-Ring |
| url | https://pubmed.ncbi.nlm.nih.gov/42184468/ |