Selective Generation of Singlet Oxygen in Chloride Accelerated Copper Fenton Chemistry

Abstract

<p>Singlet oxygen (<sup>1</sup>O<sub>2</sub>), a widely used reactive oxygen species (ROS) in industry and biomedical applications, plays a fundamental role throughout nature. We report a novel method to generate <sup>1</sup>O<sub>2</sub>selectively and efficiently through copper-based Fenton chemistry under circumneutral conditions enhanced by chloride as co-catalyst, with reactivity completely different than that observed in classical iron-based Fenton chemistry. The mechanism of its formation was elucidated through the kinetic studies of orthogonally reactive reporter molecules, i.e., singlet oxygen sensor green, 4-hydroxy-2,2,6,6-tetramethylpiperidine, and phenol, and selective ROS quenchers. This method selectively generates <sup>1</sup>O<sub>2</sub><i>in situ</i>neither relying on photosensitization nor resulting in side reactions, and together with the mechanistic understanding of the Cu-Fenton reaction, not only opens new possibilities in many industries, such as organic synthesis and antimicrobial treatments, but also provides insight into Cu and H<sub>2</sub>O<sub>2</sub>containing chemical, environmental, and biological systems.</p>

Nanoreporter of an Enzymatic Suicide Inactivation Pathway

“…[ROS detection reagent] = 10 μM, [dopamine] = 1 mM; n = 3, mean ± SEM; **** P < 0.0001, *** P = 0.0004, unpaired t test. (C) Schematic of copper Fenton reaction with respective quenchers (figure adapted from Carrier et al 2018). (D) ROS detection reagent fluorescence during incubation with TYR–CNTs and 1 mM dopamine together with ROS scavengers for 60 min.…”

Synergistic Multimodal Cancer Therapy Using Glucose Oxidase@CuS Nanocomposites

“…34 Recently, our group discovered that chloride ions accelerate Cu-based Fenton chemistry (Cl−Cu Fenton), 35 generating reactive species including hydroxyl and chlorine radicals and singlet oxygen. 12,36,37 This effect was observed for both Cu ions and CuO NPs, and the effect of chloride on ROS production has been further investigated in other systems with differing results. 38−40 We hypothesize that chloride-accelerated Cu-Fenton may also apply to the catalytic activity of CuS NPs in the tumor sites, especially when Gox is introduced simultaneously to produce H 2 O 2 in situ.…”

“…CuS NPs are promising low-temperature photothermal and photodynamic therapeutics, excellent contrast agents for photoacoustic and magnetic resonance imaging, , and promising radiotherapy sensitizers . Recently, our group discovered that chloride ions accelerate Cu-based Fenton chemistry (Cl–Cu Fenton), generating reactive species including hydroxyl and chlorine radicals and singlet oxygen. ,, This effect was observed for both Cu ions and CuO NPs, and the effect of chloride on ROS production has been further investigated in other systems with differing results. − We hypothesize that chloride-accelerated Cu-Fenton may also apply to the catalytic activity of CuS NPs in the tumor sites, especially when Gox is introduced simultaneously to produce H 2 O 2 in situ. In addition, because NIR irradiation can generate electron–hole pairs and the Cu-Fenton reaction rate increases with temperature, we believe that the photothermal effect from NIR irradiation of CuS NPs will enhance radical generation, resulting in a more effective and efficient treatment (Scheme ).…”

“…Gox catalyzes glucose oxidation using molecular oxygen to form gluconic acid and hydrogen peroxide (H 2 O 2 ) (eq ). Gox can therefore suppress tumor growth by depleting glucose, i.e., cancer starvation therapy (ST). , This also lowers the local pH of tumor sites and generates H 2 O 2 , which not only is toxic by itself to tumor cells but also serves as a precursor to generate even more toxic reactive oxygen, chlorine, and nitrogen species (reactive oxygen species (ROS), RCS, and RNS), e.g., singlet oxygen ( 1 O 2 ), , hydroxyl radicals ( • OH), hypochlorous acid (HOCl), and nitric oxide (NO), through Fenton-like reactions. These reactive species can kill tumor cells more efficiently than H 2 O 2 .…”