绿光光控释放和荧光增强响应的CO给体设计、合成及应用

doi:10.6023/cjoc202407023

研究论文

绿光光控释放和荧光增强响应的CO给体设计、合成及应用

邢皖晋^*,a,b, 张逸蓉^a, 陈军伟^a, 励扬^a, 徐缓^b, 王卫^*,a, 楼开炎^*,a

^a华东理工大学药学院上海 200237;
^b安徽理工大学公共卫生学院合肥 232001

收稿日期:2024-07-10 修回日期:2024-10-12
基金资助:
上海市自然科学基金基金(No. 20ZR1414700 ),国家自然科学基金(No. 42177417 )资助项目.

Design, Synthesis, and Application of CO Donor with Green Light Triggered Release and Fluorescence Turn-on Response

Xing Wanjin^*,a,b, Zhang Yirong^a, Chen Junwei^a, Li Yang^a, Xu Huan^b, Wang Wei^*,a, Lou Kaiyan^*,a

^aSchool of Pharmacy, East China University of Science & Technology, Shanghai 200237;
^bSchool of Public health, Anhui University of Science and Technology, Hefei 232001

Received:2024-07-10 Revised:2024-10-12
Contact: * E-mail: 859118500@qq.com
Supported by:
Shanghai Natural Science Fund (No. 20ZR1414700), National Natural Science Foundation of China (No. 42177417)

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摘要/Abstract

一氧化碳（CO）不仅是一种有毒气体,同时也是重要的气体信号传递分子,在多种生理和病理过程中发挥重要的调节作用,包括神经传递、血管扩张、减缓炎症反应、抗癌等。发展可控释放并能产生荧光信号定量示踪的CO给体分子对于研究其信号传导和量效关系尤为重要。本文以3-羟基黄酮醇（HF）为光控释放CO基团,通过在B环4’位以双键共轭连接方式引入氟硼二吡咯（BODIPY）荧光团,设计合成了一种新型绿光光解和荧光示踪的光控CO给体分子BODIPY-Fla-1。它能在绿色LED光源照射的有氧条件下光解生成CO,同时在562 nm处产生绿色荧光增强响应,可通过荧光成像对其在细胞内的光控释放CO进行示踪。我们也在细胞氧化应激模型中,验证了BODIPY-Fla-1光控释放CO可有效降低细胞内超氧自由基水平,缓解氧化应激。这种以双键共轭的方式连接荧光团的策略为进一步开发光解波长更长可荧光示踪的3-黄酮醇光控CO给体分子提供了新的分子设计思路。

关键词: 一氧化碳, 荧光给体, 光控释放, 氧化应激, 绿色荧光

Carbon monoxide (CO) is not only a toxic gas, but also an important gas signaling molecule that plays crucial regulatory roles in various physiological and pathological processes, which include neurotransmission, vasodilation, mitigation of inflammatory response, and anti-cancer activities. Therefore, development of CO donors for controlled release of CO with simutaneous fluorescence signal generation for quantification and tracking purpose is particularly useful for CO signal transduction and quantity-activity relationship studies. Herein, a novel photo-controlled CO donor BODIPY-Fla-1 was designed and synthesized using 3-hydroxyflavone (HF) as the photo-triggered CO-releasing moiety, which is conjugated to a boron-dipyrromethene (BODIPY) fluorophore at its 4’ position of B ring via a double-bond linkage. It can achieve photo- triggered CO release under green LED light irradiation and aerobic condition with simutaneous fluorescence turn-on responses at 562 nm for convenient tracking CO release via fluorescence imaging at green channel in live cell studies. It was also verified that the CO released by photolysis of BODIPY-Fla-1 can effectively reduce the level of intracellular superoxide radical and alleviate oxidative stress. This incorporation of a conjugated fluorophore moiety via a double bond linkage provides a new design strategy for development of HF-based CO donors with longer photolysis light and fluorescence response wavelength.

Key words: carbon monoxide, CO donor, photo-triggered release, oxiditive stress, green fluorescence

引用此文

邢皖晋, 张逸蓉, 陈军伟, 励扬, 徐缓, 王卫, 楼开炎. 绿光光控释放和荧光增强响应的CO给体设计、合成及应用[J]. 有机化学, doi: 10.6023/cjoc202407023.

Xing Wanjin, Zhang Yirong, Chen Junwei, Li Yang, Xu Huan, Wang Wei, Lou Kaiyan. Design, Synthesis, and Application of CO Donor with Green Light Triggered Release and Fluorescence Turn-on Response[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202407023.

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参考文献

[1] Owens, E. O. Clin. Biochem. 2010, 43, 1183.
[2] Morse D.; Sethi J. Antioxid. Redox Signaling 2002, 4, 331.
[3] Sjöstrand, T. Scand. J. Clin. Lab. Invest. 1949, 1, 201.
[4] Walewska A.; Szewczyk A.; Koprowski P. Int. J. Mol. Sci. 2018, 19, 3227.
[5] Motterlini R.; Foresti R. Am. J. Physiol. Cell Physiol. 2017, 312, C302.
[6] Otterbein L. E.; Foresti R.; Motterlini R. Circ.Res. 2016, 118, 1940.
[7] Ryter, S. W. Arch. Biochem. Biophys. 2019, 678: 108186.
[8] Goebel U.; Wollborn J. Intens.Care Med. Exp. 2020, 8, 2.
[9] Zhou Y.; Yu W.; Cao J.; Gao, h. Biomaterials 2020, 255, 120193.
[10] Popova M.; Soboleva T.; Arif A. M.; Berreau L. M. RSC Adv. 2017, 7, 21997.
[11] Christopher P.; Hopper L. M.; Christoph Steiger.; Leo E. Otterbein. Curr. Pharm. Des. 2018, 24, 2264.
[12] Fagone P.; Mangano K.; Coco M.; Perciavalle V.; Garotta G.; Romao C. C.; Nicoletti F. Clin. Exp. Immunol. 2012, 167, 179.
[13] Anderson S. N.; Richards J. M.; Esquer H. J.; Benninghoff A. D.; Arif A. M.; Berreau L. M.Chem. Open 2015, 4, 590.
[14] Gonzalez M. A.; Fry N. L.; Burt R.; Davda R.; Hobbs A.; Mascharak P. K. Inorg. Chem. 2011, 50, 3127.
[15] Fujita K.; Tanaka Y.; Sho T.; Ozeki S.; Abe S.; Hikage T.; Kuchimaru T.; Kondoh S. K.; Ueno T. J. Am. Chem. Soc. 2014, 136, 16902.
[16] Margarita A.; Gonzalez N. L.F.; Richard, Burt.; Riddhi, Davda.; Adrian, Hobbs.; Pradip, K. Mascharak. Inorg. Chem. 2011, 50, 3127.
[17] Wang P.; Liu H.; Zhao Q.; Chen Y. L.; Liu B.; Zhang B. P.; Zheng Q. Eur. J. Med. Chem. 2014, 74, 199.
[18] Min Q.; Ji X. Chem. Med. Chem. 2023, 18, e202200500.
[19] Palao E.; Slanina T.; Muchová L.; Šolomek T.; Vítek L.; Klán, P. J. Am. Chem. Soc. 2016, 138, 126.
[20] Sitnikov N. S.; Li Y.; Zhang D.; Yard B.; Schmalz H. G. Angew. Chem. Int.Ed. 2015, 54, 12314.
[21] Ji X.; Zhou C.; Ji K.; Aghoghovbia R. E.; Pan Z. X.; Chittavong V.; Ke B. W.; Wang B. H. Angew. Chem. Int.Ed. 2016, 55, 15846.
[22] Romão C. C.; Blättler W. A.; Seixas J. D.; Bernardes G. J. Chem. Soc. Rev. 2012, 41, 3571.
[23] Perez, Vizcaino, F.; Duarte, J. Mol. Aspects Med. 2010, 31, 478.
[24] Zenkevich I. G.; Eshchenko A. Y.; Makarova S. V.; Vitenberg A. G.; Dobryakov Y. G.; Utsal V. A. Molecules 2007, 12, 654.
[25] Zhao X.;Li X.; Liang, S.; Dong, X. W.; Zhang, Z. RSC Adv. 2021, 11, 28851.
[26] Feng W.; Feng S.; Feng G. Chem.Commun. 2019, 55, 8987.
[27] Štacková L.; Russo M.; Muchová L.; Orel V.; Vítek L.; Štacko P.; Klán, P. Chem. Eur. J. 2020, 26, 13184.
[28] Zhang Y.; Sun Y. J.; Yu C.; Li Y. Q. Org. Biomol. Chem. 2023, 21, 4297.
[29] Ulrich G.; Ziessel R.; Harriman A. Angew. Chem. Int. Ed. 2008, 47, 1184.
[30] Wang H.; Xu Y.; Rao L.; Yang C. T.; Yuan H.; Gao T. J.; Chen X.; Sun H. Y.; Xian M.; Liu C. R.; Liu C. L. Anal. Chem. 2019, 91, 5646.
[31] Kim B.; Fukuda M.; Lee J. Y.; Su D. D.; Sanu S.; Silvin A.; Khoo A. T.; Kwon T.; Liu X.; Chi W. J.; Liu X. G.; Choi S.; Wan D. S.; Park S. J.; Kim J. S.; Ginhoux F.; Je H. S.; Chang Y. T. Angew. Chem. Int.Ed. 2019, 58, 7972.
[32] Yan J. W.; Zhu, J. Y; Tan, Q. F.; Zhou L. F.; Yao P. F.; Lu Y. T.; Tan J. H.; Zhang L. RSC Adv. 2016, 6, 65373.
[33] He Q.; Kiesewetter D. O.; Qu Y.; Fu X.; Fan J.; Huang P.; Liu Y. J.; Zhu G. Z.; Liu Y.; Qian Z. Y.; Chen X.Y. Adv. Mater. 2015, 27, 6741.
[34] Zhao H. T.; Zhang H.; Joseph J.; Nithipatikom K.Free Radical Biol. Med. 2003, 34, 1359.