Photo-physical, theoretical and photo-cytotoxic evaluation of a new class of lanthanide(iii)–curcumin/diketone complexes for PDT application

Abstract

Herein we report the synthesis, characterization, photophysical and photocytotoxicity studies of a new class of curcumin-based lanthanide(III) complexes of general molecular formula [La(1,10-phen)₂(L)(NO₃)₂] (1–4), where L = 1-phenylbutane-1,3-dione (L¹, 1), 1-(anthracen-9-yl)butane-1,3-dione (L², 2), 1-(3a¹,5a¹-dihydropyren-1-yl)butane-1,3-dione (L³, 3) and curcumin (L⁴, 4). Complex 1 was characterized by single-crystal X-ray crystallography and it exhibited the N4O6 coordination of La(III). The presence of the low-lying and long-lived triplet excited state enabled the luminescent complexes (2–4) to generate singlet oxygen (¹O₂) in high yield when the complex was activated with visible light (400–700 nm, 10 J cm⁻²), which could be responsible for the photo-ablation of cancer cells. Complexes (2–4) exhibited remarkable photocytotoxicity in HeLa and MCF-7 cells with photocytotoxicity index 4–50 in the presence of visible light (400–700 nm, 10 J cm⁻²), while they were non-toxic in the dark with an IC₅₀ value of >100 μM. The significantly lower toxicity (IC₅₀ > 100 μM in the dark; IC₅₀ in visible light ∼60 μM) of the complexes in MCF-10A (normal cells) in the dark and in visible light suggested their potential for targeting anticancer activity. Further studies showed that complex 4 induced caspase-dependent apoptosis through mitochondrial damage, mitochondrial respiration inhibition and reactive oxygen species (ROS) elevation. The cytosolic localization of complex 4 in HeLa cells, having a curcumin moiety as a fluorophore, was proved from the confocal microscopic studies. The photocytotoxicity of the complexes (1–4) was directly correlated to the efficacy of the complexes to generate singlet oxygen, which resulted in the photocytotoxicity order of 4 > 3>2 ≫ 1. Photo-physical studies revealed that the chelation of curcumin by La(III) facilitated intersystem crossing in curcumin by reducing the energy gap of the singlet to triplet excited state. Therefore, the presence of low-lying and long-lived triplet excited state was responsible for increasing the generation of singlet oxygen and, thereby, photo-cytotoxicity in HeLa and MCF-7 cells. The present study has given an overall (Chemistry to Biology) perspective on the effect of La(III) on the photo-cytotoxicity of selected photo-active curcumin-based β-diketonate ligands.