Rational Design of an Ultrasensitive and Highly Selective Chemodosimeter by a Dual Quenching Mechanism for Cysteine Based on a Facile Michael‐Transcyclization Cascade Reaction. Issue 27 (31st May 2016)

• Record Type: Journal Article
• Authors: Li, Xiangmin; Zheng, Yongjun; Tong, Hongjuan; Qian, Rui; Zhou, Lin; Liu, Guixia; Tang, Yun; Li, Hao; Lou, Kaiyan; Wang, Wei
• Is Part Of: Chemistry. Volume 22:Issue 27(2016)
• Page Start: 9247
• Page End: 9256
• Publication Date: 2016-05-31
• Subjects: cascade reactions -- chemodosimeter -- click chemistry -- cysteine -- fluorescent probes; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201601126
• Languages: English
• ISSNs: 0947-6539

Abstract

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. Abstract : Magic cascade for high selectivity : The judicious selection of a strong electron‐withdrawing naphthalimide fluorophore turns generally nonselective fluorogenic maleimides into an ultrasensitive and highly selective chemodosimeter for cysteine over other biothiols including Hcy and GSH and other amino acids. The unique thiol‐Michael/transcyclization cascade reaction and imbeded dual PET and ICT quenching mechanism are critical for high selectivity (see scheme).