title: Rational Design of an Ultrasensitive and Highly Selective Chemodosimeter by a Dual Quenching Mechanism for Cysteine Based on a Facile Michael-Transcyclization Cascade Reaction.
abstract: Differentiation of biologically important thiols, such as cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) is still a challenging task. Herein, we present a novel fluorescent chemodosimeter capable of selectively detecting Cys over other biothiols including Hcy and GSH and other amino acids by a facile thiol-Michael addition/transcyclization rearrangement cascade click process. The unique transcyclization step is critical for the selectivity as a result of the kinetically favorable formation of a six-membered ring with the Cys Michael adduct. Moreover, the probe adopts a distinctive dual quenching mechanism-photoinduced electron transfer (PET) and photoinduced intramolecular charge transfer (ICT) to deliver a drastic turn-on fluorescence response only at the Cys-selective transcylization step. The judicious selection of strong electron-withdrawing naphthalimide fluorophore with maleimide group enhances the electrophilicity and thus reactivity for the cascade process leading to fast detection and ultrasensitivity with a detection limit of 2.0 nm (S/N=3). The probe has demonstrated its practical utility potential in Cys imaging in live cells.
authors.affiliation: Shanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, P. R. China.|Department of Chemistry & Chemical Biology, University of New Mexico, MSC03 2060, Albuquerque, NM, 87131-0001, USA.
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, P. R. China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Shanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, P. R. China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Tong
authors.affiliation: Shanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, P. R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Qian
authors.affiliation: Department of Chemistry & Chemical Biology, University of New Mexico, MSC03 2060, Albuquerque, NM, 87131-0001, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Shanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, P. R. China.
authors.forename: Guixia
authors.initials: G
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, P. R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Shanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, P. R. China. hli77@ecust.edu.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, P. R. China. kylou@ecust.edu.cn.
authors.forename: Kaiyan
authors.initials: K
authors.lastname: Lou
authors.affiliation: Shanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, P. R. China. wwang@unm.edu.|Department of Chemistry & Chemical Biology, University of New Mexico, MSC03 2060, Albuquerque, NM, 87131-0001, USA. wwang@unm.edu.
authors.forename: Wei
authors.identifier: http://orcid.org/0000-0001-6043-0860
authors.initials: W
authors.lastname: Wang
mesh_terms: D057930:Click Chemistry; D003500:Cyclization; D003545:Cysteine / Q000032:analysis / Q000737:chemistry*; D004579:Electron Transport; D005456:Fluorescent Dyes / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry*; D005978:Glutathione / Q000737:chemistry; D006367:HeLa Cells; D006710:Homocysteine / Q000737:chemistry; D006801:Humans; D057230:Limit of Detection; D008301:Maleimides / Q000737:chemistry; D008856:Microscopy, Fluorescence; D011789:Quantum Theory; D013050:Spectrometry, Fluorescence
chemical_list: D005456:Fluorescent Dyes; D008301:Maleimides; D006710:Homocysteine; C043592:maleimide; D005978:Glutathione; D003545:Cysteine
keywords: cascade reactions; chemodosimeter; click chemistry; cysteine; fluorescent probes