Design of bis-spiropyran ligands as dipolar molecule receptors and application to in vivo glutathione fluorescent probes.
Despite considerable efforts toward the development of various sophisticated spiropyrans for metal ion sensing, less attention has been paid to organic molecule sensing. One of the major difficulties for detection of organic molecules using a spiropyran is the weak and nonspecific interaction between the spiropyran and the target. Here, we report the synthesis and molecular recognition characterization of two bis-spiropyrans for dipolar molecules and their application to in vivo glutathione (GSH) fluorescent probes. Unlike the mono-spiropyrans, the newly designed bis-spiropyran molecules feature a rigidly maintained molecular cleft and two spiropyran units as binding modules. The molecular recognition is based on multipoint electrostatic interactions and structure complementarity between the opened merocyanine form of the spiropyran and the analyte. It was observed that the spiropyran 1a binds GSH in aqueous solution with high affinity (K = (7.52 +/- 1.83) x 10(4) M(-1)) and shows strong fluorescence emission upon binding. Remarkably, fluorescence output of 1a is not significantly affected by other amino acids and peptides, especially, structurally similar compounds, such as cysteine and homocysteine. Furthermore, fluorescence anisotropy and confocal fluorescent microscopy confirmed that spiropyran 1a is a comparatively good candidate for intracellular delivery and can be accumulated intensively into cells. Thus, 1a can be utilized in vivo as a GSH probe or as a marker to show the level of intracellular GSH.
Shao
Na
N
Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
Jin
Jianyu
J
Wang
Hao
H
Zheng
Jing
J
Yang
Ronghua
R
Chan
Winghong
W
Abliz
Zeper
Z
D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry; D005978:Glutathione / Q000032:analysis*; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D008024:Ligands; D015394:Molecular Structure; D009574:Nitro Compounds / Q000138:chemical synthesis* / Q000737:chemistry
D001578:Benzopyrans; D005456:Fluorescent Dyes; D007211:Indoles; D008024:Ligands; D009574:Nitro Compounds; C088184:spiropyran; D005978:Glutathione