Xanthene-Based Nitric Oxide-Responsive Nanosensor for Photoacoustic Imaging in the SWIR Window.

Shortwave infrared (SWIR) dyes are characterized by their ability to absorb light from 900 to 1400 nm, which is ideal for deep tissue imaging owing to minimized light scattering and interference from endogenous pigments. An approach to access such molecules is to tune the photophysical properties of known near-infrared dyes. Herein, we report the development of a series of easily accessible (three steps) SWIR xanthene dyes based on a dibenzazepine donor conjugated to thiophene (SCR-1), thienothiophene (SCR-2), or bithiophene (SCR-3). We leverage the fact that SCR-1 undergoes a bathochromic shift when aggregated for in vivo studies by developing a ratiometric nanoparticle for NO (rNP-NO), which we employed to successfully visualize pathological levels of nitric oxide in a drug-induced liver injury model via deep tissue SWIR photoacoustic (PA) imaging. Our work demonstrates how easily this dye series can be utilized as a component in nanosensor designs for imaging studies.

Thienylpiperidine Donor NIR Xanthene-Based Dye for Photoacoustic Imaging.

Few xanthene-based near-infrared (NIR) photoacoustic (PA) dyes with absorbance >800 nm exist. As accessibility to these dyes requires long and tedious synthetic steps, we designed a NIR dye (XanthCR-880) with thienylpiperidine donors and a xanthene acceptor that is accessible in 3-4 synthetic steps. The dye boasts a strong PA signal at 880 nm with good biological compatibility and photostability, yields multiplexed imaging with an aza-BODIPY reference dye, and is detected at a depth of 4 cm.

Donor-Acceptor-Donor NIR II Emissive Rhodindolizine Dye Synthesized by C-H Bond Functionalization.

A NIR II emissive dye was synthesized by the C-H bond functionalization of 1-methyl-2-phenylindolizine with 3,6-dibromoxanthene. The rhodindolizine (RhIndz) spirolactone product was nonfluorescent; however, upon opening of the lactone ring by the formation of the ethyl ester derivative, the fluorophore absorbs at 920 nm and emits at 1092 nm, which are both in the NIR II region. In addition, 4-cyanophenyl- (CNRhIndz) and 4-methoxyphenyl-substituted rhodindolizine (MeORhIndz) could also be prepared by the C-H activation reaction.