Tuning optical properties, charge transfer and anticancer activity of curcumin-cyanine conjugates: A combined...

Despite curcumin's potential for photosensitizer design, its low stability in the aqueous phase and lack of charge-transfer properties have prevented its application in photodynamic therapy (PDT). We rationally designed four curcumin-monomethine cyanine conjugates (4a-d) using synthetic and computational strategies to explore the effects of heterocycle engineering on their photophysical and anticancer properties. The dyes were developed using pyrazole or oxazole curcumin cores by N-methylation and coupling to quinaldinium or lepidinium electron acceptors, and characterized using FTIR, NMR, ESI-MS, and elemental analysis. All conjugates showed strong, tunable visible absorption in ethanol (λ_max 494-656 nm) with high molar absorptivities and pH-switchable intramolecular charge transfer, which is appropriate for activation in acidic tumor environments. The ground state geometries, frontier molecular orbitals, and low-lying excited states were evaluated using density functional theory (DFT) analyses. The results showed that the 4d oxazole ring and quinolinium terminus enabled HOMO-LUMO separation, larger transition dipole moments, and stabilized intramolecular charge transfer (ICT) excited states, favoring light harvesting and charge/energy transfer. Global reactivity indices, Mulliken charge, and Fukui function revealed that 4d had the highest electrophilicity and polarizability, along with defined nucleophilic and electrophilic sites, which are suitable for non-covalent interactions and photo-induced redox reactions. Micromolar cytotoxicity was noted against PC3 and MCF-7 cancer cells for all dyes in vitro, with the benzothiazole derivative 4d being the most potent (IC₅₀ ∼ 10 μM in MCF-7 cells). Overall, oxazole curcumin-cyanine 4d can serve as a promising pH-responsive visible light photosensitizer for future PDT development.