A photoacoustic Zn2+ sensor based on a merocyanine/xanthene-6-ol hybrid chromophore and its ratiometric imaging in mice

Abstract

Accurate tracking of labile Zn²⁺ fluctuation in vivo is essential for understanding the physiological and pathological functions of Zn²⁺. Photoacoustic (PA) Zn²⁺ imaging is an attractive alternative for in vivo labile Zn²⁺ tracking due to its larger tissue imaging depth than optical imaging, and exploring reliable design strategies to construct ratiometric sensors for Zn²⁺. PA imaging is especially demanded to overcome the interference from deviations of local sensor concentration and microenvironment. In this work, we designed a new ratiometric reversible PA sensor HD-Zn based on a merocyanine/2,3-dihydro-1H-xanthene-6-ol hybrid chromophore, with its phenol moiety being modified as a Zn²⁺ chelator, 2-(bis(pyridin-2-ylmethyl)amino)phenol (BPAP). HD-Zn senses Zn²⁺ in a ratiometric manner, showing an absorbance enhancement at 680 nm and a concomitant absorbance decrement at 750 nm. This endowed the sensor with ratiometric PA sensing ability for Zn²⁺. Zn²⁺ titration experiments and theoretical study indicated that Zn²⁺ chelation-induced ICT alteration of HD-Zn was responsible for the ratiometric PA sensing ability, and modifying the electron-donating hydroxyl group of this hybrid NIR chromophore to be a Zn²⁺ chelator is a reliable strategy for constructing ratiometric PA sensors for Zn²⁺. Besides the ratiometric PA imaging ability for Zn²⁺ in solution, HD-Zn also enables ratiometric PA imaging of labile Zn²⁺ in living mice.