A Unique “Integration” Strategy for the Rational Design of Optically Tunable Near-Infrared Fluorophores

Abstract

Fluorescence imaging is a rapidly growing technique for noninvasive imaging of biological molecules and processes with high spatial and temporal resolution. For effective biological imaging, it is essential and important to develop robust fluorescent dyes, in particular, near-infrared (NIR) fluorescent dyes with favorable optical properties. Compared with the visible light emitting dyes, NIR dyes have relatively longer emission wavelengths (650-900 nm) with lower energy and are advantageous as imaging agents owing to the minimum photodamage of NIR light to biological samples, deep penetration into tissues, and low interference from autofluorescence of biomolecules. Although great efforts have been devoted to engineer NIR fluorophores, it is still very challenging to regulate their photophysical properties as they often lack optically tunable mechanisms, and this shortcoming considerably restricts the realization of their full potential. Consequently, the rational design of small-molecule optically tunable NIR fluorophores is of high priority and great value. In general, two key characteristics are indispensable for designing excellent optically tunable NIR fluorescent dyes. First, NIR fluorescent dyes should display the maximal absorption and emission located in the NIR region and also have the prominent properties including excellent fluorescence quantum yields, large Stokes shifts, good chemical stability and photostability, low cytotoxicity, and desirable compatibility with biological systems. Second, in principle, functional NIR dyes should also possess optically tunable groups, which can be easily modified to afford responsive sites for the targets of interest. With these considerations in mind, in this Account, we described a unique "integration" strategy for judicious design of the optically tunable NIR fluorophores, which are an intuitive combination of the traditional NIR dyes and the optically tunable mechanisms in the visible light emissive dyes. Thus, the versatile strategy may allow not only retention of the NIR emission properties of NIR dyes but also inheritance of the optically tunable mechanisms from the visible light emissive dyes. By the unique integration strategy, a built-in optically tunable group is strategically installed into the traditional NIR fluorescent dyes to directly tune their optical properties. Herein, we present a concise review of the rational design strategy and biological applications of small-molecule optically tunable NIR fluorescent dyes via the unique integration strategy, and we focused mainly on our work and some representative examples from other groups based on our NIR platforms. This Account includes the detailed integration strategy of each class of the NIR fluorescent dyes, the development of their derivatives, and their imaging applications in living systems.

Rational Design of a Robust Fluorescent Probe for the Detection of Endogenous Carbon Monoxide in Living Zebrafish Embryos and Mouse Tissue

“…Thus, we envisioned that it is necessary to design new fluorescent CO probes with advantageous features such as much higher stability and longer emission wavelengths. In general, fluorescent probes with high stability may be favorable for decreasing the background fluorescence, and probes with longer emission wavelengths are desirable for imaging in living organisms . Based on these considerations, in this work, we focused on the Nile Red ( NR ) dye for design of novel fluorescent CO probes, as it has several merits including a large, rigid π‐structure, potential heteroatoms for complexing with Pd, and a long emission wavelength.…”

Rational Design of a Robust Fluorescent Probe for the Detection of Endogenous Carbon Monoxide in Living Zebrafish Embryos and Mouse Tissue

“…Zuschriften decreasing the background fluorescence,a nd probes with longer emission wavelengths are desirable for imaging in living organisms. [13] Based on these considerations,i nt his work, we focused on the Nile Red (NR)d ye for design of novel fluorescent CO probes,asithas several merits including alarge,rigid p-structure,potential heteroatoms for complexing with Pd, and al ong emission wavelength. Thus,w e reasoned that the new type of CO probes, NR-Pd,may have much higher stability and longer emission wavelengths when compared to the current CO probes (Scheme 1b).…”

Towards NIR‐Active Hydroxybenzazole (HBX)‐Based ESIPT Motifs: A Recent Research Trend

“…Hence, NIR fluorophores have emerged as promising modalities in monitoring in‐vitro and in‐vivo levels of several biologically important species . Several NIR active fluorophores have been developed such as cyanine, merocyanine, rhodamine, BODIPY, squaraine, benzophenoxazines, porphyrins, and many more . Such types of fluorophores exhibit self‐absorption or inner filter effect and it should be avoided to improve the fluorescence analysis this can be done by having a fluorophores with large Stokes shift.…”

“…[24,25] Several NIR active fluorophores have been developed such as cyanine, merocyanine, rhodamine, BODIPY, squaraine, benzophenoxazines, porphyrins, and many more. [26][27][28][29][30][31][32][33][34][35][36] Such types of fluorophores exhibit self-absorption or inner filter effect and it should be avoided to improve the fluorescence analysis this can be done by having a fluorophores with large Stokes shift. It is difficult to increase a Stokes shift of conventional fluorophores by chemical modification.…”