Nickel/Photoredox-Catalyzed Asymmetric Reductive Cross-Coupling of Racemic α-Chloro Esters with Aryl Iodides

A unique nickel/organic photoredox co-catalyzed asymmetric reductive cross-coupling between α-chloro esters and aryl iodides is developed. This cross-electrophile coupling reaction employs an organic reductant (Hantzsch ester), whereas most reductive cross-coupling reactions use stoichiometric metals. A diverse array of valuable α-aryl esters is formed under these conditions with high enantioselectivities (up to 94 %) and good yields (up to 88 %). α-Aryl esters represent an important family of nonsteroidal anti-inflammatory drugs. This novel synergistic strategy expands the scope of Ni-catalyzed reductive asymmetric cross-coupling reactions.     

Polymeric Encapsulation of Novel Homoleptic Bis(dipyrrinato) Zinc(II) Complexes with Long Lifetimes for Applications as Photodynamic Therapy Photosensitisers

The use of photodynamic therapy (PDT) to treat cancer has received increasing attention over the last years. However, the clinically used photosensitisers (PSs) have some limitations that include poor aqueous solubility, hepatotoxicity, photobleaching, aggregation, and slow clearance from the body, so the design of new classes of PSs is of great interest. We present the use of bis(dipyrrinato)zinc(II) complexes with exceptionally long lifetimes as efficient PDT PSs. Based on the heavy‐atom effect, intersystem crossing of these complexes changes the excited state from singlet to a triplet state, thereby enabling singlet oxygen generation. To overcome the limitation of quenching effects in water and improve water solubility, the lead compound 3 was encapsulated in a polymer matrix. It showed impressive phototoxicity upon irradiation at 500 nm in various monolayer cancer cells as well as 3D multicellular tumour spheroids, without observed dark toxicity.     

A Cross‐linked Conjugated Polymer Photosensitizer Enables Efficient Sunlight‐Induced Photooxidation

Photooxidation under sunlight has potential in organic synthesis, bacterial killing, and organic waste treatment. Photosensitizers (PSs) can play an important role in this process. High ¹O₂ generation efficiency and excellent photostability under sunlight, as well as easy recyclability are ideal properties for PSs, but are not easy to achieve simultaneously. Herein, a pure organic porous conjugated polymer PS, CPTF, shows great photostability, large specific surface area, and high ¹O₂ generation efficiency under sunlight for photooxidation. For the oxidation of aromatic aldehyde to aromatic acid, the PS catalyst shows excellent recyclability, and enables solvent‐free reactions in high yields both under direct sunlight and simulated AM 1.5G irradiation. In addition, the successful application of CPTF as an antibacterial agent and organic waste decomposition under simulated AM 1.5G irradiation indicates the potential of CPTF in sunlight‐induced waste water treatment.     

An Activatable Photosensitizer Targeted to γ‐Glutamyltranspeptidase

We adopted a spirocyclization‐based strategy to design γ‐glutamyl hydroxymethyl selenorhodamine green (gGlu‐HMSeR) as a photo‐inactive compound that would be specifically cleaved by the tumor‐associated enzyme γ‐glutamyltranspeptidase (GGT) to generate the potent photosensitizer HMSeR. gGlu‐HMSeR has a spirocyclic structure and is colorless and does not show marked phototoxicity toward low‐GGT‐expressing cells or normal tissues upon irradiation with visible light. In contrast, HMSeR predominantly takes an open structure, is colored, and generates reactive oxygen species upon irradiation. The γ‐glutamyl group thus serves as a tumor‐targeting moiety for photodynamic therapy (PDT), switching on tumor‐cell‐specific phototoxicity. To validate this system, we employed chick chorioallantoic membrane (CAM), a widely used model for preliminary evaluation of drug toxicity. Photoirradiation after gGlu‐HMSeR treatment resulted in selective ablation of implanted tumor spheroids without damage to healthy tissue.     

Stimuli‐Responsive Reversible Switching of Intersystem Crossing in Pure Organic Material for Smart Photodynamic Therapy

Photosensitizers (PSs) with stimuli‐responsive reversible switching of intersystem crossing (ISC) are highly promising for smart photodynamic therapy (PDT), but achieving this goal remains a tremendous challenge. This study introduces a strategy to obtain such reversible switching of ISC in a new class of PSs, which exhibit stimuli‐initiated twisting of conjugated backbone. We present a multidisciplinary approach that includes femtosecond transient absorption spectroscopy and quantum chemical calculations. The organic structures reported show remarkably enhanced ISC efficiency (Φ_ISC), switching from nearly 0 to 90 %, through an increase in the degree of twisting, providing an innovative mechanism to promote ISC. This leads us to propose here and demonstrate the concept of smart PDT, where pH‐induced reversible twisting maximizes the ISC rate, and thus enables strong photodynamic action only under pathological stimulus (such as change in pH, hypoxia, or exposure to enzymes). The ISC process is turned off to deactivate PDT ability, when the PS is transferred or metabolized away from pathological region.     

Near‐IR‐Triggered,Remote‐Controlled Release of Metal Ions: A Novel Strategy for Caged Ions

A ligand incorporating a dithioethenyl moiety is cleaved into fragments which have a lower metal‐ion affinity upon irradiation with low‐energy red/near‐IR light. The cleavage is a result of singlet oxygen generation which occurs on excitation of the photosensitizer modules. The method has many tunable factors that could make it a satisfactory caging strategy for metal ions.