Microwave-Assisted Synthesis of the Red-Shifted Pentamethine Tetrahydroxanthylium Core with Absorbance within the Near Infrared-II Window.

ABSTRACT

Thirteen red-shifted pentamethine dimethyl and diethylamino tetrahydroxanthylium derivatives have been successfully synthesized via the microwave-assisted approach. The optimized conditions developed in the synthesis provided an excellent yield in expedited reaction time. These newly synthesized dyes show well-defined optical properties resulting from the diverse substitutions at the central meso positions. The majority of the compounds have a maximum wavelength of absorbance within 946-1022 nm with extinction coefficients in the range of 9700-110,680 M-1 cm-1 in various solvents such as MeOH, EtOH, DMSO, DCM, MeCN, and DMF. These fluorophores, to the best of our knowledge, are the first NIR-II small molecules synthesized using microwave chemistry. We also investigated these dyes for their NIR fluorescence imaging capabilities. Diethylamino-substituted compounds and bromination resulted in higher uptake in the adrenal gland compared to dimethylamino fluorophores. In addition, micellar structures of compounds 7 and 15 improved the targetability of the original dyes to the bone marrow, lymph nodes, and nerves. Overall, NIR-II imaging has the potential to visualize biologically targeted tissues in living organisms.