Azaphosphinate Dyes: A Low Molecular Weight Near-Infrared Scaffold for Development of Photoacoustic and Fluorescence Imaging Probes

Near-infrared (NIR) dyes are desirable for biological imaging applications including photoacoustic and fluorescence imaging. Nonetheless, current NIR dyes are often plagued by relatively large molecular weights, poor water solubility, and limited photostability. Herein, we provide the first examples of azaphosphinate dyes. These dyes display maximal absorbance and emission above 750 nm and the inclusion of a phosphinate functionality virtually abolishes aggregation in aqueous solutions compared to the parent dye scaffold. The dramatically improved water solubility of this dye class enables applications in both photoacoustic and fluorescence imaging. In the case of photoacoustic imaging, we demonstrate 4.1-fold enhanced signal intensity compared to commonly used standards, the ability to multiplex with existing dyes in blood samples, and imaging depths of 2.75 cm in tissue. An improved derivative for fluorescence imaging displayed substantially reduced photobleaching compared to the FDA-approved indocyanine green dye and could be used to selectively label mitochondria in living cells. To the best of our knowledge, azaphosphinate dyes are the lowest molecular weight, water soluble dyes with absorbance and emission in the 750 nm range. This new dye class provides a robust scaffold for the development of photoacoustic and NIR fluorescence imaging agents.