Synthesis and Characterization of Novel Thienothiadiazole-Based D-π-A-π-D Fluorophores as Potential NIR Imaging Agents

As fluorescence bioimaginghas increased in popularity, there havebeen numerous reports on designing organic fluorophores with desirableproperties amenable to perform this task, specifically fluorophoreswith emission in the near-infrared II (NIR-II) region. One such strategyis to utilize the donor-& pi;-acceptor-& pi;-donorapproach (D-& pi;-A-& pi;-D), as thisallows for control of the photophysical properties of the resultingfluorophores through modulation of the highest occupied molecularorbital (HOMO) and the lowest unoccupied molecular orbital (LUMO)energy levels. Herein, we illustrate the properties of thienothiadiazole(TTD) as an effective acceptor moiety in the design of NIR emissivefluorophores. TTD is a well-known electron-deficient species, butits use as an acceptor in D-& pi;-A-& pi;-Dsystems has not been extensively studied. We employed TTD as an acceptorunit in a series of two fluorophores and characterized the photophysicalproperties through experimental and computational studies. Both fluorophoresexhibited emission maxima in the NIR-I that extends into the NIR-II.We also utilized electron paramagnetic resonance (EPR) spectroscopyto rationalize differences in the measured quantum yield values anddemonstrated, to our knowledge, the first experimental evidence ofradical species on a TTD-based small-molecule fluorophore. Encapsulationof the fluorophores using a surfactant formed polymeric nanoparticles,which were studied by photophysical and morphological techniques.The results of this work illustrate the potential of TTD as an acceptorin the design of NIR-II emissive fluorophores for fluorescence bioimagingapplications.

Automated summary

As fluorescence bioimaging has gained popularity, there have been many studies on designing organic fluorophores with desirable properties for this task, particularly in the near-infrared II region. One effective strategy is to use the donor-π-acceptor-π-donor approach, which allows control of the photophysical properties of the fluorophores by modulating the energy levels of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO). This study demonstrates the potential of thienothiadiazole (TTD) as an effective acceptor moiety for designing near-infrared emissive fluorophores, and provides experimental evidence of previously unexplored radical species on TTD-based small-molecule fluorophores.