Hybrid Rhodamine Fluorophores in the Visible/NIR Region for Biological Imaging

Abstract

Fluorophores and probes are invaluable for the visualization of the location and dynamics of gene expression, protein expression, and molecular interactions in complex living systems. Rhodamine dyes are often used as scaffolds in biological labeling and turn‐on fluorescence imaging. To date, their absorption and emission spectra have been expanded to cover the entire near‐infrared region (650–950 nm), which provides a more suitable optical window for monitoring biomolecular production, trafficking, and localization in real time. This review summarizes the development of rhodamine fluorophores since their discovery and provides strategies for modulating their absorption and emission spectra to generate specific bathochromic‐shifts. We also explain how larger Stokes shifts and dual‐emissions can be obtained from hybrid rhodamine dyes. These hybrid fluorophores can be classified into various categories based on structural features including the alkylation of amidogens, the substitution of the O atom of xanthene, and hybridization with other fluorophores.

Deep Red Emissive Carbonized Polymer Dots with Unprecedented Narrow Full Width at Half Maximum

“…It has been repeatedly proved that optical imaging quality is remarkably improved when progressing to longer wavelength emission, such as deep red/NIR window or two‐photon fluorescence. [ 14 − 16 ] The deep red/NIR region benefits from minimum autofluorescence and light scattering by tissues, offering great imaging contrast and spatial resolution. At present, reports on deep red/NIR emissive CDs are exclusively limited by low QY and visible light excitation, hampering the deep tissue imaging using deep red/NIR CDs.…”

A Deep‐Red to Near Infrared (NIR) Fluorescent Probe Based on a Sulfur‐Modified Rhodamine Derivative with Two Spirolactone Rings

“…[12,13] Recently, rhodamine-based probes have been of great interest in the development as NIR imaging agents considering their ease of synthesis, bright fluorescence, excellent photostability, and high quantum yield. [14][15][16][17][18] Moreover, the cationic nature allows for good water solubility and cell membrane permeability which render these organic dyes to be highly suitable as biological markers and fluorescent probes. In view of the fact that rhodamine B and rhodamine 6G are not suitable as NIR fluorescent dyes with the absorption and fluorescence maxima below 600 nm, there have been great efforts to shift their absorption and fluorescence wavelengths to deep red to NIR regions [17,19] Lowering the energy gap between the lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO) can lead to the shift of fluorescence to longer wavelengths.…”

“…[14][15][16][17][18] Moreover, the cationic nature allows for good water solubility and cell membrane permeability which render these organic dyes to be highly suitable as biological markers and fluorescent probes. In view of the fact that rhodamine B and rhodamine 6G are not suitable as NIR fluorescent dyes with the absorption and fluorescence maxima below 600 nm, there have been great efforts to shift their absorption and fluorescence wavelengths to deep red to NIR regions [17,19] Lowering the energy gap between the lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO) can lead to the shift of fluorescence to longer wavelengths. Hence, two main strategies have been developed; extending the π-conjugation system [17] or replacing the 10-position oxygen atom with quaternary C or Si atoms, as shown by carbon-modified rhodamines and silicon-modified rhodamines.…”

“…In view of the fact that rhodamine B and rhodamine 6G are not suitable as NIR fluorescent dyes with the absorption and fluorescence maxima below 600 nm, there have been great efforts to shift their absorption and fluorescence wavelengths to deep red to NIR regions [17,19] Lowering the energy gap between the lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO) can lead to the shift of fluorescence to longer wavelengths. Hence, two main strategies have been developed; extending the π-conjugation system [17] or replacing the 10-position oxygen atom with quaternary C or Si atoms, as shown by carbon-modified rhodamines and silicon-modified rhodamines. [17,[20][21][22][23][24] Although the latter method is particular interesting since a one-atom modification can elicit a dramatic shift to a longer wavelength, the synthetic difficulty limits the development of such class of probe.…”

“…Hence, two main strategies have been developed; extending the π-conjugation system [17] or replacing the 10-position oxygen atom with quaternary C or Si atoms, as shown by carbon-modified rhodamines and silicon-modified rhodamines. [17,[20][21][22][23][24] Although the latter method is particular interesting since a one-atom modification can elicit a dramatic shift to a longer wavelength, the synthetic difficulty limits the development of such class of probe.…”