Indolizine Donor-Based Dyes for Applications in Fluorescence Biological Imaging

NIR emissive fluorophores are intensely researched due to their potential to replace modern imaging procedures. Many molecular strategies have been employed in the literature to optimize fluorophores for deeper NIR absorption and emission, biocompatibility, and higher fluorescence quantum yields. Amongst the fluorophores studied to date, proaromatic indolizine donors are attractive alternatives to traditional alkyl amine and indoline based donors due to their 1) lower energy absorption and emission facilitated by proaromaticity, 2) large Stokes shifts due to increased dihedral angles about the π-system, 3) ease of functionalization and capacity for bioconjugation at the phenyl ring, and 4) potential for further red shifting via the placement of additional donors on the indolizine heterocycle. Herein, indolizine donors are incorporated into multiple common fluorophore moieties including squaraine-, cyanine-, and xanthene-based systems, and their photophysical properties studied. The indolizine donor allows for a diverse array of synthetic schemes, acting as both a nucleophile and CH activation coupling partner. Key results from indolizine donor-based fluorophores discussed herein include further red shifted cyanine absorbances compared to the ubiquitous benzindole cyanine, ICG, deep NIR-I absorption and NIR-II emission when incorporated into xanthene-based moieties, and low toxicity, high aqueous photostability, and record setting quantum yields in a biologically relevant medium.