The development of fluorescent biosensors with high sensitivity, selectivity, and biocompatibility is of critical importance to bioscience and biotechnology because it offers a direct visualization tool for the detection of biological macromolecules and the monitoring of biological events under real and living conditions. Most of the conventional organic fluorophores exhibit remarkably bright emission in their dilute solutions but become weakly or even nonemissive when aggregated or in solid state, which has greatly limited the scope of their applications....[ Read more ]

The development of fluorescent biosensors with high sensitivity, selectivity, and biocompatibility is of critical importance to bioscience and biotechnology because it offers a direct visualization tool for the detection of biological macromolecules and the monitoring of biological events under real and living conditions. Most of the conventional organic fluorophores exhibit remarkably bright emission in their dilute solutions but become weakly or even nonemissive when aggregated or in solid state, which has greatly limited the scope of their applications.

An opposite phenomenon has recently been discovered: a group of nonluminescent molecules are induced to emit efficiently by aggregate formation. “Aggregation-induced emission” (AIE) is coined for this novel effect. Attracted by the intriguing phenomenon and its fascinating perspectives, we have launched a new program directed towards the development of new AIE materials and exploration of their biological applications.

A new class of water-soluble AIE luminogens are designed and synthesized. Hydrophilic groups such as hydroxyl, sulfonate, and amino groups are introduced to make the AIE molecules readily soluble in water. Being practically non-emissive in water, these AIE dyes are lightened up when bound to biomacromolecules, such as proteins and DNA, thus enabling the quantitation and visualization of biomacromolecules in aqueous solutions and in electrophoretic gels.

The AIE luminogens are sensitive to microenvironment inside the biomolecules and their fluorescent intensity can readily reflect the global stability of the biomolecules. In this work, we employ the AIE luminogens as fluorescent reporters for the monitoring of G-quadruplex DNA folding, protein unfolding by denaturant and protein misfolding into amyloid fibrils. Thanks to the AIE characteristics, the delicate information on the conformational transition of the biomolecules can be revealed.

In addition, lipophilic AIE luminogens form highly emissive nanoaggregates when dispersed in aqueous media. Through molecular endeavor, the AIE nanoaggregates can be utilized for metal sensing and cell imaging with high sensitivity and selectivity.