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

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.