An innovative stepwise activated coupling reaction for fabricating functional fluorescence probes with potential photosensitive applications

Abstract

Coupling bright organic emitters with biocomponents such as proteins and amino acids to fabricate biocompatible optical functional materials is receiving increasing attention. Previous reports of an efficient, typical reaction between maleic anhydride (MAH) and amino groups indicated that MAH derivatives have great potential for bioconjugation applications. However, the obstacle of complex synthesis methods and weak fluorescence to this kind of derivative structures based on MAH, have greatly limited their applications. Herein, an innovative strategy was developed based on stepwise activated coupling via a multi-step process. First, a series of donor–acceptor emitting frameworks was constructed by introducing different commercially available electron donors into the electron-withdrawing squaric acid core. Then, these frameworks were further activated to obtain different 3,4-diaryl MAH precursors for bioconjugation, which contributed to a novel light-triggered ring-enlargement effect. Importantly, the MAH precursors triggered catalyst-free coupling reactions at ambient temperature with organic small molecules and biological macromolecules containing primary amine groups. Different fluorescent precursors and abundant biological components were effectively combined, and a water-soluble, biocompatible photosensitizer with efficient photodynamic and photothermal therapy effects was obtained. This strategy is expected to have great potential for biological imaging and theragnostic applications.