A six-membered-ring incorporated Si-rhodamine for imaging of copper(ii) in lysosomes.
The regulation of copper homeostasis in lysosomes of living cells is closely related to various physiological and pathological processes. Thus, it is of urgent need to develop a fluorescent probe for selectively and sensitively monitoring the location and concentration of lysosomal Cu(2+). Herein, a six-membered ring, thiosemicarbazide, was incorporated into a Si-rhodamine (SiR) scaffold for the first time, affording a SiR-based fluorescent probe SiRB-Cu. Through the effective Cu(2+)-triggered ring-opening process, the probe exhibits fast NIR chromogenic and fluorogenic responses to Cu(2+) within 2 min as the result of formation of a highly fluorescent product SiR-NCS. Compared with a five-membered ring, the expanded ring retains great tolerance to H(+), ensuring the superior sensitivity with a detection limit as low as 7.7 nM and 200-fold enhancement of relative fluorescence in the presence of 1.0 equiv. of Cu(2+) in pH = 5.0 solution, the physiological pH of lysosome. Moreover, the thiosemicarbazide moiety acts not only as the chelating and reactive site, but also as an efficient lysosome-targeting group, leading to the proactive accumulation of the probe into lysosomes. Taking advantage of these distinct properties, SiRB-Cu provides a functional probe suitable for imaging exogenous and endogenous lysosomal Cu(2+) with high imaging contrast and fidelity.
Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai 200433, China. wangting1983927@gmail.com.
Baogang
B
Wang
Department of Chemistry, New York University, New York, New York 10003, USA.
Xiaoyan
X
Cui
Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai 200433, China. wangting1983927@gmail.com.
Zhiqiang
Z
Zhang
Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai 200433, China. wangting1983927@gmail.com.
Xiaoyun
X
Chai
Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai 200433, China. wangting1983927@gmail.com.
Hao
H
Ding
Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai 200433, China. wangting1983927@gmail.com.
Qiuye
Q
Wu
Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai 200433, China. wangting1983927@gmail.com and Department of Chemistry, Wayne State University, Detroit, Michigan 48202, USA. zwguo@chem.wayne.edu.
Zhongwu
Z
Guo
Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai 200433, China. wangting1983927@gmail.com.
Ting
T
Wang
D003300:Copper / Q000032:analysis*; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D057230:Limit of Detection; D008247:Lysosomes / Q000737:chemistry* / Q000648:ultrastructure; D061986:MCF-7 Cells; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D061848:Optical Imaging; D012235:Rhodamines / Q000737:chemistry*; D012825:Silicon / Q000737:chemistry*; D013050:Spectrometry, Fluorescence
D005456:Fluorescent Dyes; D012235:Rhodamines; D003300:Copper; D012825:Silicon