THQ–Xanthene: An Emerging Strategy to Create Next‐Generation NIR‐I/II Fluorophores

Abstract

Near‐infrared fluorescence imaging is vital for exploring the biological world. The short emissions (<650 nm) and small Stokes shifts (<30 nm) of current xanthene dyes obstruct their biological applications since a long time. Recently, a potent and universal THQ structural modification technique that shifts emission to the NIR‐I/II range and enables a substantial Stokes shift (>100 nm) for THQ‐modified xanthene dyes is established. Thus, a timely discussion of THQ–xanthene and its applications is extensive. Hence, the advent, working principles, development trajectory, and biological applications of THQ–xanthene dyes, especially in the fields of fluorescence probe‐based sensing and imaging, cancer theranostics, and super‐resolution imaging, are introduced. It is envisioned that the THQ modification tactic is a simple yet exceptional approach to upgrade the performance of conventional xanthene dyes. THQ–xanthene will advance the strides of xanthene‐based potentials in early fluorescent diagnosis of diseases, cancer theranostics, and imaging‐guided surgery.

Chemical Approaches to Optimize the Properties of Organic Fluorophores for Imaging and Sensing

“…Most classical and widely adopted fluorophores, such as rhodamine, rhodol, BODIPY, oxazine, and cyanine, only possess small Stokes shift (<30 nm), [80] which results in severe overlap between the excitation and emission spectrum. The overlap brings out the fluorescence self‐quenching, further reducing the signal‐to‐noise ratio of imaging, which limits the application of these fluorophores for complex bioimaging, for instance, single‐excitation multicolor imaging [1b,10c,81] …”

Benzobisthiadiazole-Based Small Molecular Near-Infrared-II Fluorophores: From Molecular Engineering to Nanophototheranostics

“…On the contrary, organic small molecular NIR-II fluorophores manifest promising prospects for clinical application because of their definite chemical structures and superior metabolism behavior. 24,25 Up to now, well-known categories of small molecular NIR-II dyes mainly incorporate diketopyrrolopyrrole (DPP) derivatives, 26 cyanine dyes, 27 xanthene derivatives, 28,29 romethene boron difluoride (BODIPY)/ aza-BODIPY derivatives, 30−32 together with benzobisthiadiazole-based dyes. 33,34 The donor−acceptor−donor (D-A-D)-type fluorophores have garnered significant scholarly attention, owing to their exceptional photophysical characteristics with the inherent intramolecular charge transfer (ICT) effect.…”

“…However, the clinical application of inorganic nanomaterials in NIR-II FLI is hindered by biosafety concerns such as poor biocompatibility, difficult excretion, and immunogenic response. On the contrary, organic small molecular NIR-II fluorophores manifest promising prospects for clinical application because of their definite chemical structures and superior metabolism behavior. , Up to now, well-known categories of small molecular NIR-II dyes mainly incorporate diketopyrrolopyrrole (DPP) derivatives, cyanine dyes, xanthene derivatives, , dipyrromethene boron difluoride (BODIPY)/ aza-BODIPY derivatives, − together with benzobisthiadiazole-based dyes. , …”

Aza-BODIPY with two efficacious fragments for NIR light-driven photothermal therapy by triggering cancer cell apoptosis

“…6–10 Near-infrared (NIR) light can enhance tissue penetration and reduce background fluorescence interference, which is favorable for effective PTT applications with minimal adverse effects. 11–20 Boron dipyrromethene (BODIPY) and its derivatives are a well-known category of chromophores that have attracted increasing attention owing to their exceptional photophysical features and easily modifiable structures. 21–35 In contrast to BODIPY, aza-borondipyrromethene (aza-BODIPY), substituting the C atom at meso -site of BODIPY for the N atom, was first created by M. Rogers in 1943 (Fig.…”