Sustainable Approach to Methine-Substituted Heptamethine Cyanines from Bioderived Furfural and Their Phototherapy Potential

Heptamethine cyanines with substituents on the methine chain (methine-substituted Cy7) play an indispensable and central role in biology and photomedicine. However, their synthesis is still based on fossil raw materials against the backdrop of the increasing scarcity of fossil resources and the environmental issues associated with the extraction and consumption of hydrocarbons. Furthermore, the synthesis also requires relatively expensive or difficultly available reagents, relies on multistep reactions, and undergoes harsh reaction conditions. Herein, a mild one-pot synthesis of methine-substituted Cy7 from cheap and easily available renewable bioderived furfural is described. It involves reacting a mixture of furfural, aniline, aniline hydrochloride, anhydride, and quaternary ammonium salt under mild conditions to afford a series of methine-substituted Cy7 (gamma-acyloxy-Cy7) in moderate to good yields. The resulting gamma-acyloxy-Cy7 absorbs and emits in the range of 752-995 nm and 773-1023 nm, respectively, with a fluorescence quantum yield up to 68.9% relative to ICG in DMSO. Some of the gamma-acyloxy-Cy7 also exhibit good photothermal properties, having potential in fluorescence imaging and imaging-guided photothermal therapy.