An expansion of the Aza-BODIPY scaffold: Rationale-based synthesis of derivatives for tuning the NIR potential bioimaging applications via modulation of electron-donating substituents (EDGs)

Boron-dipyrromethene (BODIPY) dyes are a class of organoboron compounds that have been cited as candidates for explorations into fluorescence imaging, photodynamic therapy, and optoelectronics. The meso-modified analog, Aza-BODIPY has become ubiquitous in biomedical applications due to the propensity to tune physicochemical and spectral properties by varying hydrophobic and hydrophilic substituents. One modality of imaging is photoacoustic (PA) imaging, which combines the features of optical and ultrasound imaging, absorbs near-infrared light (NIR) to excite a PA probe to cause tissue expansion and induce pressure, which subsequently allows for the generation of ultrasound wave for detection. Compared with fluorescence imaging, ultrasound waves confer the advantage of less autofluorescence of biological tissues, due to less photons scattering, which facilitate deeper tissue penetration (>3 cm). As a result, PA agents are notable for greater accuracy and visual result compared to solely optical imaging. This research reports probative results and aim of the synthesis of Aza-BODIPY dyes as activatable PA probes with respect to their absorbance and fluorescence optical properties and density-functional theory (DFT) computational studies. Herein, we synthesized and evaluated 14 Aza-BODIPY dyes with respect to purely optical imaging; however, preliminary screenings reveal little to no fluorescence of such agents, rendering them futile for optical fluorescence imaging. However, the inclination to utilize as PA probes is a promising advent. This research is the culmination of aim to design Aza-BODIPY dyes for tumor targeting and bioimaging that redshifted to NIR-II region and confer good optoacoustic properties.