Book Description

Small molecule organic dyes with absorption and emission in the near infrared region (NIR) attracted much attention for various applications such as dye sensitized solar cells, fluorescent guided surgery, stimuli responsive bioimaging and photodynamic therapy. Dyes with high absorption and emission in the NIR region are beneficial for stimuli responsive bioimaging due to the deeper penetration of NIR light, less cell damage, high resolution, and low background autofluorescence from biomolecules. Of the many small molecule dyes, xanthene-based dyes exhibit outstanding photophysical properties and good stimuli response for use in bioimaging applications. However, absorption and emission of the xanthene dyes lie in the visible region, which limit their applications in cellular imaging. Many of the NIR dyes have very poor fluorescence; consequently, an alternative approach to fluorescent imaging is photoacoustic imaging that uses sound waves to generate pictures of deep tissues. In this dissertation, we discuss the utility of xanthene based NIR dyes as photoacoustic imaging contrast agents for multiplex imaging and deep tissue nitric oxide sensing in the drug-induced liver injury. Chapter I discuss the fundamentals of fluorescence and photoacoustic imaging, background of the xanthene dyes and other fluorescent dyes, and the design strategies to develop NIR xanthene-based dyes. Chapter II is based on our approach to the design and synthesis of NIR xanthene-based dyes by C-H bond functionalization, with the first example being Rhodindolizine, which absorb and emits in NIR II or short-wave infrared (SWIR) region. In chapter III, we describe the design and synthesis of thienylpiperidine xanthene-based NIR and shortwave-infrared (SWIR) dyes for the photoacoustic imaging. One dye in particular (XanthCR-880) 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. In chapter IV, we report a series of SWIR dyes based on a dibenzazepine donor conjugated to thiophene (SCR-1, SCR-4), thienothiophene (SCR-2, SCR-5), and bithiophene (SCR-3, SCR-6). We leverage the fact that SCR-1 undergoes a bathochromic shift when aggregated to develop a ratiometric nanoparticle for nitric oxide (NO) (rNP-NO). rNP-NO was used to successfully perform in vivo studies to visualize pathological levels of nitric oxide in a drug-induced liver injury model via deep tissue SWIR photoacoustic (PA) imaging. Chapter V describes another series of xanthene-based dyes with a thiophene þ̀± spacer and several different donors. UV-Vis absorption studies were performed after converting the dyes to the opened form with trifluoracetic acid. These novel XanthCR-TD dyes exhibit absorption maxima in NIR I region from 700 - 900 nm.