Synthesis of a Novel Pyrazine–Pyridone Biheteroaryl-Based Fluorescence Sensor and Detection of Endogenous Labile Zinc Ions in Lung Cancer Cells
A small extent of endogenous labile zinc is involved in many vital physiological roles in living systems. However, its detailed functions have not been fully elucidated. In this study, we developed a novel biheteroaryl-based low molecular weight fluorescent sensor, 3-(phenylsulfonyl)-pyrazine...
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MDPI AG
2019-05-01
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| Series: | Sensors |
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| Online Access: | https://www.mdpi.com/1424-8220/19/9/2049 |
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| author | Masayori Hagimori Mana Taniura Naoko Mizuyama Yasushi Karimine Shigeru Kawakami Hideo Saji Takahiro Mukai |
| author_facet | Masayori Hagimori Mana Taniura Naoko Mizuyama Yasushi Karimine Shigeru Kawakami Hideo Saji Takahiro Mukai |
| author_sort | Masayori Hagimori |
| collection | DOAJ |
| description | A small extent of endogenous labile zinc is involved in many vital physiological roles in living systems. However, its detailed functions have not been fully elucidated. In this study, we developed a novel biheteroaryl-based low molecular weight fluorescent sensor, 3-(phenylsulfonyl)-pyrazine−pyridone (<b>5b</b>), and applied it for the detection of endogenous labile zinc ions from lung cancer cells during apoptosis. The electron-withdrawing property of the sulfonyl group between the phenyl ring as an electron donor and the pyridone ring as a fluorophore inhibited the intramolecular charge transfer state, and the background fluorescence of the sensor was decreased in aqueous media. From the structure−fluorescence relationship analysis of the substituent effects with/without Zn<sup>2+</sup>, compound <b>5b</b> acting as a sensor possessed favorable properties, including a longer emission wavelength, a large Stokes shift (over 100 nm), a large fluorescence enhancement in response to Zn<sup>2+</sup> under physical conditions, and good cell membrane permeability in living cells. Fluorescence imaging studies of human lung adenocarcinoma cells (A549) undergoing apoptosis revealed that compound <b>5b</b> could detect endogenous labile zinc ions. These experiments suggested that the low molecular weight compound <b>5b</b> is a potential fluorescence sensor for Zn<sup>2+</sup> toward understanding its functions in living systems. |
| first_indexed | 2024-04-11T22:46:57Z |
| format | Article |
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| issn | 1424-8220 |
| language | English |
| last_indexed | 2024-04-11T22:46:57Z |
| publishDate | 2019-05-01 |
| publisher | MDPI AG |
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| series | Sensors |
| spelling | doaj.art-241996374d23494ba846fc117fe096572022-12-22T03:58:44ZengMDPI AGSensors1424-82202019-05-01199204910.3390/s19092049s19092049Synthesis of a Novel Pyrazine–Pyridone Biheteroaryl-Based Fluorescence Sensor and Detection of Endogenous Labile Zinc Ions in Lung Cancer CellsMasayori Hagimori0Mana Taniura1Naoko Mizuyama2Yasushi Karimine3Shigeru Kawakami4Hideo Saji5Takahiro Mukai6Department of Biophysical Chemistry, Kobe Pharmaceutical University, 4-19-1 Motoyamakita Machi, Higashinada Ku, Kobe 658-8558, JapanDepartment of Biophysical Chemistry, Kobe Pharmaceutical University, 4-19-1 Motoyamakita Machi, Higashinada Ku, Kobe 658-8558, JapanClinical Research Center, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, JapanGraduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, JapanGraduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, JapanGraduate School of Pharmaceutical Sciences, Kyoto University, 46–29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, JapanDepartment of Biophysical Chemistry, Kobe Pharmaceutical University, 4-19-1 Motoyamakita Machi, Higashinada Ku, Kobe 658-8558, JapanA small extent of endogenous labile zinc is involved in many vital physiological roles in living systems. However, its detailed functions have not been fully elucidated. In this study, we developed a novel biheteroaryl-based low molecular weight fluorescent sensor, 3-(phenylsulfonyl)-pyrazine−pyridone (<b>5b</b>), and applied it for the detection of endogenous labile zinc ions from lung cancer cells during apoptosis. The electron-withdrawing property of the sulfonyl group between the phenyl ring as an electron donor and the pyridone ring as a fluorophore inhibited the intramolecular charge transfer state, and the background fluorescence of the sensor was decreased in aqueous media. From the structure−fluorescence relationship analysis of the substituent effects with/without Zn<sup>2+</sup>, compound <b>5b</b> acting as a sensor possessed favorable properties, including a longer emission wavelength, a large Stokes shift (over 100 nm), a large fluorescence enhancement in response to Zn<sup>2+</sup> under physical conditions, and good cell membrane permeability in living cells. Fluorescence imaging studies of human lung adenocarcinoma cells (A549) undergoing apoptosis revealed that compound <b>5b</b> could detect endogenous labile zinc ions. These experiments suggested that the low molecular weight compound <b>5b</b> is a potential fluorescence sensor for Zn<sup>2+</sup> toward understanding its functions in living systems.https://www.mdpi.com/1424-8220/19/9/2049endogenous Zn<sup>2+</sup>pyrazine–pyridone biheteroaryllow background fluorescencesulfonyl groupcellular imaging |
| spellingShingle | Masayori Hagimori Mana Taniura Naoko Mizuyama Yasushi Karimine Shigeru Kawakami Hideo Saji Takahiro Mukai Synthesis of a Novel Pyrazine–Pyridone Biheteroaryl-Based Fluorescence Sensor and Detection of Endogenous Labile Zinc Ions in Lung Cancer Cells Sensors endogenous Zn<sup>2+</sup> pyrazine–pyridone biheteroaryl low background fluorescence sulfonyl group cellular imaging |
| title | Synthesis of a Novel Pyrazine–Pyridone Biheteroaryl-Based Fluorescence Sensor and Detection of Endogenous Labile Zinc Ions in Lung Cancer Cells |
| title_full | Synthesis of a Novel Pyrazine–Pyridone Biheteroaryl-Based Fluorescence Sensor and Detection of Endogenous Labile Zinc Ions in Lung Cancer Cells |
| title_fullStr | Synthesis of a Novel Pyrazine–Pyridone Biheteroaryl-Based Fluorescence Sensor and Detection of Endogenous Labile Zinc Ions in Lung Cancer Cells |
| title_full_unstemmed | Synthesis of a Novel Pyrazine–Pyridone Biheteroaryl-Based Fluorescence Sensor and Detection of Endogenous Labile Zinc Ions in Lung Cancer Cells |
| title_short | Synthesis of a Novel Pyrazine–Pyridone Biheteroaryl-Based Fluorescence Sensor and Detection of Endogenous Labile Zinc Ions in Lung Cancer Cells |
| title_sort | synthesis of a novel pyrazine pyridone biheteroaryl based fluorescence sensor and detection of endogenous labile zinc ions in lung cancer cells |
| topic | endogenous Zn<sup>2+</sup> pyrazine–pyridone biheteroaryl low background fluorescence sulfonyl group cellular imaging |
| url | https://www.mdpi.com/1424-8220/19/9/2049 |
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