title: A dual emission fluorescent probe enables simultaneous detection of glutathione and cysteine/homocysteine.
abstract: Many studies have shown that glutathione (GSH) and cysteine (Cys) / homocysteine (Hcy) levels are interrelated in biological systems. To unravel the complicated biomedical mechanisms by which GSH and Cys/Hcy are involved in various disease states, probes that display distinct signals in response to GSH and Cys/Hcy are highly desirable. In this work, we report a rhodol thioester (1) that responds to GSH and Cys/Hcy with distinct fluorescence emissions in neutral media. Probe1reacts with Cys/Hcy to form the corresponding deconjugated spirolactam via a tandem native chemical ligation (NCL) reaction. This intramolecular spirocyclization leads to the "quinone - phenol" transduction of rhodol dyes, and an excited-state intramolecular proton transfer (ESIPT) process between the phenolic hydroxyl proton and the aromatic nitrogen in the benzothiazole unit occurs upon photoexcitation, thus affording 2-(2'-hydroxyphenyl) benzothiazole (HBT) emission (454 nm). In the case of the tripeptide GSH, only transthioesterification takes place removing the intramolecular photo-induced electron transfer (PET) process caused by the electron deficient 4-nitrobenzene moiety giving rise to a large fluorescence enhancement at the rhodol emission band (587 nm). The simultaneous detection of GSH and Cys/Hcy is attributed to the significantly different rates of intramolecular S,N-acyl shift of their corresponding thioester adducts derived from1. The utility of probe1has been demonstrated in various biological systems including serum and cells.
authors.affiliation: Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry & Materials Science, Northwest University, Xi'an 710069, P.R. China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Yang
authors.affiliation: Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry & Materials Science, Northwest University, Xi'an 710069, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Huang
authors.affiliation: College of Life Sciences, Northwest University, Xi'an 710069, P.R. China.
authors.forename: Yaogang
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: College of Life Sciences, Northwest University, Xi'an 710069, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry & Materials Science, Northwest University, Xi'an 710069, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Chemistry, Portland State University, Portland, OR, 97201, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Lowry
authors.affiliation: Department of Chemistry, Portland State University, Portland, OR, 97201, USA.
authors.forename: Jorge O
authors.initials: JO
authors.lastname: Escobedo
authors.affiliation: Department of Chemistry, Portland State University, Portland, OR, 97201, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Strongin