Text Box: Chen group 
陈以昀课题组
Text Box: State Key Laboratory of Bioorganic and Natural Products Chemistry
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences
中国科学院上海有机化学研究所生命有机化学国家重点实验室

research

We develop new biocompatible visible-light-induced chemical methods to study biology, including the discovery of new visible-light-induced chemical reactions and the development of new optochemical biology tools. Traditionally, biological applications of photochemical reactions used direct irradiation on substrates with UV light, which required the use of biologically harmful UV light and light-absorbing substrates. We use visible-light-absorbing photocatalysts/photosensitizers to induce electron/energy transfer with non-visible-light-absorbing substrates, or form visible-light-absorbing donor–acceptor complexes from non-visible-light-absorbing substrates (Fig. 1). These new light-induced reaction modes enable additional desirable characteristics for biocompatible reactions: i) Stable substrates with fast reaction kinetics; ii) Versatile bond formation and cleavage reactions; and iii) External modulation with high temporal and spatial precision.

Fig. 1 The strategy to study biocompatible visible-light-chemistry.

 

1. New Chemical Reactivity Discovery from Visible-Light-Chemistry

(i) Cyclic iodine(III) reagent hydroxylbenziodoxole (BI-OH) in visible-light-chemistry:

We have reported cyclic iodine(III) reagent hydroxylbenziodoxole (we term it BI-OH) as the effective oxidative photocatalytic quencher for the first time, and also reported the transition-metal-like carboxylate and alcohol activation reactivity for the first time (Fig. 2). 

Fig. 2 The research accomplishments of cyclic iodine(III) reagent hydroxylbenziodoxole (BI-OH) from Chen’s group.

(ii) Alkoxyl radical in visible-light-chemistry:

We have reported the first visible-light-induced alkoxyl radical generations from alcohol derivatives (2015) or alcohols (2016) , which enabled inert C(sp3)-H and C(sp3)-C(sp3) bond functionalization. We have also reported the C-X bond cleavage and 1,2-HAT reactivity of alkoxyl radicals in visible-light-chemistry (Fig. 3).

Fig. 3 The research accomplishments of alkoxyl radical in visible-light-chemistry from Chen’s group.

(iii) Electron donor-acceptor complex in visible-light-chemistry:

We have reported Hantzsch ester (a synthetic analogue of NADH), or boronic acids to form donor–acceptor complexes for the first time, for photocatalyst-free visible-light-induced reactions (Fig. 4).

Fig. 4 The research accomplishments of electron donor-acceptor complex in visible-light-chemistry from Chen’s group.

 

2. Biocompatibility Discovery of Visible-Light-Chemistry

(i) Biomolecule-compatibility of visible-light-chemistry:

We have reported the first oxidative photocatalytic system based on cyclic iodine(III) reagent BI-OH that is compatible with biomacromolecules even cell lysates (Fig. 5). We have also reported the first reductive photocatalytic bond-formation reaction that is compatible with biomacromolecules even cell lysatesbased on the ascorbates.

 

Fig. 5 The research accomplishments of biomolecule-compatibility of visible-light-chemistry from Chen’s group.

(ii) Bioactive small molecules photo-release by visible-light-chemistry:

We have reported boronic acids and ketoacids as building blocks for bioactive small molecules photo-release with versatile visible-light-induced bond-formation and bond cleavage reactions (Fig. 6).

Fig. 6 The research accomplishments of bioactive small molecules photo-release by visible-light-chemistry from Chen’s group.

(iii) Live-cell-compatibility of visible-light-chemistry:

Recently, optogenetics centered on photosensitive proteins have been widely accepted and applied in the biological community. The complementary optochemical biology methods centered on light-induced chemical reactions may provide molecule-level precision with light modulation. We have shown the first photocatalytic reaction in live cells for bioactive molecules release with visible light (Fig. 7). The deboronative hydroxylation is enabled by photocatalytic generation
of hydrogen peroxides with organic dyes, which performs in bacteria and mammalian cells including neurons. The subcellular-specific photorelease of bioactive molecules in live cells can be realized by mitochondria-localized photocatalysts, which cannot be realized by traditional UV light irradiation. We are currently developing versatile bond-cleavage and bond-formation reactions in live cells, which will enable optochemical manipulation of biological functions with high temporal and spatial precision.

Fig. 7 The research accomplishments of live-cell-compatibility of visible-light-chemistry from Chen’s group.