Indolizine–Squaraines: NIR Fluorescent Materials with Molecularly Engineered Stokes Shifts

Abstract

The development of deep red and near infrared emissive materials with high quantum yields is an important challenge. Several classes of squaraine dyes have demonstrated high quantum yields, but require significantly red-shifted absorptions to access the NIR window. Additionally, squaraine dyes have typically shown narrow Stokes shifts, which limits their use in living biological imaging applications due to dye emission interference with the light source. Through the incorporation of indolizine heterocycles we have synthesized novel indolizine squaraine dyes with increased Stokes shifts (up to >0.119 eV, >50 nm increase) and absorptions substantially further into the NIR region than an indoline squaraine benchmark (726 nm versus 659 nm absorption maxima). These materials have shown significantly enhanced water solubility, which is unique for squaraine dyes without water-solubilizing substituents. Absorption, electrochemical, computational, and fluorescence studies were undertaken and exceptional fluorescence quantum yields of up 12 % were observed with emission curves extending beyond 850 nm.

Water-Soluble NIR Absorbing and Emitting Indolizine Cyanine and Indolizine Squaraine Dyes for Biological Imaging

“…Among NIR emissive dyes, squaraines , and cyanines , are ubiquitous. ,, Previous research has frequently investigated indoline donor-based cyanine and squaraine dyes with indocyanine green (ICG) having been awarded FDA approval several decades ago. , Both of these classes of dyes need design strategies that allow access to longer wavelength NIR photons in aqueous environments . In fact, the indoline squaraine absorbs outside the therapeutic window, which renders it impractical for use as a noninvasive biological imaging agent . To deepen the NIR absorbing properties of these dye classes, designs capable of extending the π-system through a conjugated donor (such as indolizine) are attractive. − Recent photophysical studies using proaromatic indolizine donors in place of indoline donors show red-shifting of the absorption and emission profiles of these dyes firmly into the therapeutic window in nonaqueous environments ( C5 and SQ compared to ICG and indoline squaraine, respectively; Figure ).…”

“…In fact, the indoline squaraine absorbs outside the therapeutic window, which renders it impractical for use as a noninvasive biological imaging agent . To deepen the NIR absorbing properties of these dye classes, designs capable of extending the π-system through a conjugated donor (such as indolizine) are attractive. − Recent photophysical studies using proaromatic indolizine donors in place of indoline donors show red-shifting of the absorption and emission profiles of these dyes firmly into the therapeutic window in nonaqueous environments ( C5 and SQ compared to ICG and indoline squaraine, respectively; Figure ). − These studies indicated that in the case of phenyl-indolizine derivatives, the phenyl group does not play a significant role in tuning the absorption or emission energy values of the NIR indolizine dyes. , This enables the use of the phenyl group to append water-soluble functionality without perturbing the core chromophore properties of the dyes, permitting the probing of the photophysical properties of the dyes in aqueous environments.…”

SWIR emissive RosIndolizine dyes with nanoencapsulation in water soluble dendrimers

“…The strong donation of indolizine allows for the retention of cyanine band structuring when indolizine is used in pentamethine and squaraine core systems. [32][33][34] Recent work from our group has shown that the substitution of amines for indolizine on rhodamine led to a dramatic red-shi of the absorption and emission spectrum with SWIR emission observed. 35 However, the synthesis of the rhodindolizine was challenging and obtaining pure material from the harsh conditions required to open the lactone ring was problematic.…”

A near-infrared excitation/emission fluorescent probe for imaging of endogenous cysteine in living cells and zebrafish

“…The development of NIR fluorophore has played an important role in the optical imaging field, which allows it to become an increasing contributor to biological imaging. With the great efforts of researchers, several NIR fluorophores had been developed, such as phthalocyanines, porphyrin derivatives, squaraine derivatives, benzo[c]heterocycles, and cyanine dyes [27][28][29][30][31][32][33][34]. However, the synthesis of them was complicated and high cost, which limited their wide applications to some extent.…”