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.

Synthesis, Optical Properties, and In Vivo Biodistribution Performance of Polymethine Cyanine Fluorophores

“…However, the low MW can increase the permeability. Therefore, to predict the localization of the fluorophores in a specific tissue, permeability, cellular uptake, retention, and clearance the physicochemical properties were examined by ChemAxon (JChem plugin) . The results obtained from in silico calculations are presented in Table .…”

“…Therefore, to predict the localization of the fluorophores in a specific tissue, permeability, cellular uptake, retention, and clearance the physicochemical properties were examined by ChemAxon (JChem plugin). 27 The results obtained from in silico calculations are presented in Table 1 . Most molecular volumes of the synthesized fluorophores lied between 531 and 699 Å 3 , while their TPSA remained the same at 6.25 Å 2 .…”