Heavy-Metal Free Near Infrared Photoredox Catalysts in Cancer Phototherapy

Abstract

Herein, five new far red/near Infra-red (NIR) heavy-metal free photosensitizers (PSs) were developed by donor modulation of the planar perylenimide (PI) core, exhibiting large Stokes shifts of 213-270 nm. The dimethyl-enabled aggregation induced enhanced emission (AIEE) and tunable AIEE/AIE behaviors of the RPI PSs aided precise and efficient superoxide (O₂•⁻) generation for cancer phototherapy, viz. R = -Ph (PhPI), -PhNH2 (ANPI), -PhN(CH3)2 (DMPI), -PhN(Ph)2 (TPPI), -PhN(BiPh)2 (BPPI) to obtain distinct NIR emitters and NIR photoredox catalytic properties. Notably, the solid state NIR emissive DMPI, TPPI and BPPI showed far-red/NIR AIEE, AIE and AIEE behaviors in aqueous media, whereas PhPI and ANPI displayed aggregation-caused quenching (ACQ) effects. A key discovery is the dimethyl-induced transformation of ACQ-to-AIEE in DMPI, enabling a very rare and unusual feature of inducing NIR AIEE properties in the PS. Moreover, the ACQ molecules PhPI and ANPI generate O₂•⁻/•OH (type-I PS/photoredox) efficiently, DMPI exhibits NIR AIEE photoredox characteristics for O₂•⁻ (type-I PS) generation, TPPI illustrates far-red AIE photoredox/type-II PS for O₂•⁻/1O₂ (singlet oxygen quantum yield, ΦΔ = 0.59 in aqueous media), while BPPI demonstrated far-red AIEE photoredox for O₂•⁻ in cancer cells. These systems highlight the diverse optical and therapeutic properties obtained by carefully varying the donor moiety in the RPIs. The most prominent dimethyl-induced NIR AIEE design strategy in DMPI, reveals exceptional heavy metal-free (NIR AIEE/NIR) photoredox catalyst PS, offering precise and efficient electron transfer for O₂•⁻ production. Importantly, the NIR photoredox catalysts are rarely reported, and the introduction of NIR AIEE photoredox sensitizers expands the scope of current photoredox research. The photocatalytic superoxide generators TPPI, developed via triplet-ground-state splitting energy modulation, induce significant cancer cell death through a partial O₂-recycling pathway involving Haber-Weiss/Fenton reactions.