Hyperbranched Tetraphenylethylene Derivatives with Low Non-specific Aggregation-Induced Emission for Fluorescence Recognition of Proteins with Hydrophobic Pockets.

Proteins play an important role in the physiological process of many organisms, and their abnormal level often indicates the occurrence of some diseases. Therefore, protein analysis has important reference value and clinical significance for early diagnosis and therapy of disease. Using human serum albumin (HSA) as a model protein, a series of super-branched tetraphenylethylene (TPE) derivatives with different branching structures and terminal groups are reported herein for highly sensitive and specific recognition of proteins with hydrophobic cages. Benefiting from the hyperbranched structures, these probes showed much higher critical micelle concentrations (CMCs) than most linear TPE-based amphiphilic molecules since the hyperbranched structure not only improved their solubility but also amplified the steric hindrance effect and electrostatic repulsive force to prevent their aggregation. Dynamic light scattering experiments proved that these probes formed dense aggregates at CMC, and such aggregate structures would lead to a higher background fluorescence noise. Hence, a higher CMC is more conducive to the detection of the target with low backgrounds. Among them, P 3 -COOH with -COOH as the terminal unit and a relatively longer branch showed the highest CMC and the best signal to background ratio (S/N). Mechanism studies showed that P 3 -COOH was bound to HSA mainly through a hydrophobic force, resulting in a limited P 3 -COOH molecular movement and less attack from quenchers in solutions, thus leading to greatly enhanced fluorescence intensity. In addition, P 3 -COOH was also applied to the determination of HSA content in actual human serum samples.