Aryl-Modified Pentamethyl Cyanine Dyes at the C2' Position: A Tunable Platform for Activatable Photosensitizers

Pentamethyl cyanine dyes are promising fluorophores for fluorescence sensing and imaging. However, advanced biomedical applications require enhanced control of their excited-state properties. Herein, a synthetic approach for attaching aryl substituents at the C2' position of the thio-pentamethine cyanine (TCy5) dye structure is reported for the first time. C2'-aryl substitution enables the regulation of both the twisted intramolecular charge transfer (TICT) and photoinduced electron transfer (PET) mechanisms to be regulated in the excited state. Modulation of these mechanisms allows the design of a nitroreductase-activatable TCy5 fluorophore for hypoxic tumor photodynamic therapy and fluorescence imaging. These C2'-aryl TCy5 dyes provide a tunable platform for engineering cyanine dyes tailored to sophisticated biological applications, such as photodynamic therapy. This work reports a promising pentamethyl cyanine platform using C2'-aryl substitutions. It is found that electron-withdrawing groups enhanced twisted intramolecular charge transfer (TICT), resulting in efficient fluorescence quenching. The electron-donating groups make the TICT tendency weaken significantly, while photoinduced electron transfer is enhanced. This change improves both the fluorescence quantum yield and the intersystem crossing (ISC) efficiency.image