Push-Pull OPEs in Blue-Light Anticancer Photodynamic Therapy

Photodynamic therapy (PDT) is a minimally invasive technique-used for the local eradication of neoplastic cells-that exploits the interaction of light, oxygen, and a photo-responsive drug called photosensitizer (PS) for the local generation of lethal ROS. Push-pull chromophores, that bear electron donor (D) and acceptor (A) groups linked through a π-electron bridge, are characterized by a non-homogeneous charge distribution in their excited state, with charge transfer from one extremity of the chain to the other one (Internal Charge Transfer-ICT). This phenomenon has a direct impact on the photophysical features of the push-pull compounds, as the bathochromic shift of the emission maxima and intersystem crossing (ISC) of the excited state are directly connected with the production of reactive oxygen species (ROS). In continuing our research regarding the synthesis and use of oligophenylene ethynylenes (OPEs) in PDT, two new push-pull glycosyl OPE-NOF and OPE-ONF-featuring electron-donor N,N-dimethylamino (N) and dimetoxyaryl (O) and acceptor tetrafluoroaryl (F) moieties on the OPE chain-have been efficiently prepared. The interchanged position of the D groups onto the conjugated skeleton was aimed to tune and optimize the push-pull effect, while the introduction of glucoside terminations was directed to give biocompatibility and bioaffinity to the chromophores. OPE-NOF, OPE-ONF, and the synthetic intermediates were fully characterized, and their photophysical properties were investigated by using UV-Vis absorption and emission spectroscopy. OPE-NOF showed a strong charge-transfer character and high PDT effect on HeLa cancer cells when irradiated with non-harmful blue light, causing massive cancer cell death.