Aggregation-induced emission active seminaphthofluoresceins: a new class of xanthene luminogens for bioimaging

Abstract

The development of aggregation-induced emission (AIE) luminogens has made marked and diverse impacts in the areas of bioimaging and theragnostics. While virtually every class of traditional aggregation-caused quenching (ACQ) fluorophores have been investigated for the purposes of establishing the sought after ACQ to AIE transformation, the prolific xanthene family has remained largely overlooked. A recent brief report of simple derivatized fluoresceins exhibiting AIE characteristics upended the prevailing perception of fluoresceins as fixed ACQ species but limited progress has taken place in the years following. In this study we take the first step towards highly functional xanthene AIEgens, exploring both the nuances of aggregation and translation to applications in imaging and sensing. The synthetic modification of seminaphthofluoresceins (benzo[c]xanthenes, π-extended fluorescein derivatives) yields luminogens exhibiting high Stokes shifts, bathochromically shifted emission, and aggregation-induced emission behaviour. The optical properties of the seminaphthofluorescein propargyl ethers, possessing terminal alkyne moieties for facile customization, are assessed both in the dissolved state and throughout the aggregation process. As a result of their controlled response to non-solvents over a broad range of solution compositions, the luminogens are suited for the optical sensing of water content in organic solvents. The aggregates were utilized for organelle imaging in microglia, the immune cells of the brain, and accumulated predominantly in the mitochondria. When coupled with their limited reliance on membrane potential, these findings suggest the luminogens as novel and versatile tools for intracellular visualization, tracking, and interactions of mitochondria with other organelles.