Arunachalam Sagadevan

Metal Nanoparticles Sensitize the Formation of Singlet Oxygen

Singlet oxygen (O2) is known to play an indispensible role in the photodynamic therapy (PDT) treatment of cancer, and is an important oxidant for hydroperoxidation of olefins in organic synthesis. Singlet O2 is conventionally formed by sensitization by organic photosensitizers, such as Rose Bengal, silicon phthalocyanine, etc. These organic or organometallic dyes are, however, prone to photoinduced degradation and enzymatic degradation, which becomes problematic in PDT treatments, and reduces the efficiency of the generation of singlet O2. [5,8] It is, therefore, important to search for photosensitizers with highly efficient singlet O2 generation and large absorption coefficients that are photochemically more stable and less prone to enzymatic degradation. Previously, it was reported that the yield of singlet oxygen production by a photosensitizer, namely, Rose Bengal, was enhanced by a silver island film through the metal-enhanced absorption of photosensitizer. It was also reported that a gold nanodisk could enhance the phosphorescence decay rate of singlet oxygen, leading to a larger characteristic phosphorescence emission band of singlet oxygen at 1270 nm. In another two studies, it was observed that the quantum yield of singlet O2 formation generated by phthalocyanine photosensitizers can be enhanced by the presence of gold nanoparticles. Herein we report an unprecedented observation that singlet oxygen can be formed through direct sensitization by metal nanoparticles (M NPs, M=Ag, Pt, and Au) without the presence of any organic photosensitizers. Unambiguous experimental evidence includes direct observation of singlet oxygen emission at roughly 1268 nm, hydroperoxidation of cyclohexene, green fluorescence from a selective singlet oxygen fluorescent sensor, namely, Singlet Oxygen Sensor Green (SOSG, Molecular Probe), and quenching of singlet oxygen phosphorescence by sodium azide. As shown in Figure 1, photoexcitation of M NPs at the surface plasmon resonance absorption bands of Ag (d= 55, 42 nm), Pt (10 nm), and Au (22 nm) in D2O results in characteristic singlet oxygen emission at 1264 and 1268 nm, respectively. Control experiments show that in the absence of metal nanoparticles, photoexcitation of poly(vinyl pyrrolidone (PVP) in D2O using either 254 or 508 nm light did not result in any detectable singlet O2 emission signal (see the

Visible-light initiated copper(I)-catalysed oxidative C–N coupling of anilines with terminal alkynes: one-step synthesis of α-ketoamides

Development of C–N coupling processes is fundamentally important and challenging for the synthesis of biologically active molecules and drugs. Herein, we report a highly atom efficient green process for the synthesis of α-ketoamides via visible-light induced copper(I) chloride catalysed direct oxidative Csp–N coupling reactions using commercially available alkynes and anilines at room temperature without the use of hazardous chemicals and harsh reaction conditions. Forty-seven examples are presented using a broad range of substrates including electron deficient anilines and various terminal alkynes. The current photochemical process is able to achieve epoxide hydrolase inhibitors in one step with high yield (92–95%). This transformation is highly efficient and highly selective for the synthesis of α-ketoamides.

Photoinduced Copper-Catalyzed Regioselective Synthesis of Indoles: Three-Component Coupling of Arylamines, Terminal Alkynes, and Quinones

The first successful example of a visible-light-induced copper-catalyzed process for C-H annulation of arylamines with terminal alkynes and benzoquinone is described. This three-component reaction allows use of a variety of commercial terminal alkynes as coupling partners for the one-step regioselective synthesis of functionalized indoles. Moreover, the current process represents a sustainable and atom-economical approach for the preparation of complex indoles from easily accessible starting materials under visible-light irradiation, without the need for expensive metals and harsh reaction conditions.

Morphology dependent photosensitization and formation of singlet oxygen (1Δg) by gold and silver nanoparticles and its application in cancer treatment

Singlet oxygen is a very important reactive oxygen species (ROS) involved in peroxidation of olefins and polymers, as well as in clinical photodynamic therapy treatments of tumors. Previously, it was reported that singlet oxygen can be formed via sensitization by spherical metal nanoparticles upon photo-excitation of the surface plasmon resonance (SPR) bands. In this paper, we report that sensitization and formation of singlet O2 is strongly dependent on the morphologies of gold and silver nanostructures. For example, singlet O2 can be generated via photo-irradiation and sensitization of silver decahedrons and silver triangular nanoplates, but not by silver nanocubes and gold decahedrons. The sensitization patterns of silver and gold nanoparticles are the reverse of each other. In the case of gold nanorods, singlet O2 can be generated via photo-excitation at the longitudinal SPR band, but not by excitation at the transverse SPR band. The controlling factors for such a morphology dependent singlet O2 sensitization will be discussed. Furthermore, we also demonstrate in vitro morphology dependent sensitization behaviour of silver nanoparticles in the photodynamic cancer treatment. Our results indicate that metal nanoparticles with certain morphologies are potentially very promising dual functional nanomaterials with capabilities of simultaneously serving as near infrared (NIR) activatable photodynamic therapy and photothermal therapy reagents for cancer treatments.

Visible-light-activated copper(I) catalyzed oxidative Csp–Csp cross-coupling reaction: efficient synthesis of unsymmetrical conjugated diynes without ligands and base

A novel visible-light-promoted copper-catalysed process for the Csp–Csp cross-coupling reaction of terminal alkynes at room temperature is described. The current photochemical method is simple, highly functional group compatible, and more viable towards the construction of bio-active 1,3-unsymmetrical conjugated diynes without the need of bases/ligands, additives and expensive palladium/gold catalysts.

Visible-light-induced, copper(I)-catalysed C–N coupling between o-phenylenediamine and terminal alkynes: one-pot synthesis of 3-phenyl-2-hydroxy-quinoxalines

Visible-light-initiated aerobic direct C-N coupling between o-phenylenediamines and terminal acetylenes was performed using simple copper(I) chloride as a catalyst for the synthesis of quinoxaline derivatives. The current method works well for a wide range of electron rich as well as electron poor group-substituted o-phenylenediamines and phenylacetylenes. The key component in the reaction is the direct photo-excitation of in situ generated copper arylacetylide (λ(abs) = 420-480 nm). Moreover, as compared to the literature reports (thermal process), the current photochemical method is simple, mild, high yielding, and more viable towards the construction of biologically important quinoxaline derivatives from easily accessible raw materials, without the need of ligands and strong oxidants.

Copper(I)-catalysed oxidative C–N coupling of 2-aminopyridine with terminal alkynes featuring a CC bond cleavage promoted by visible light

Facile visible-light promoted copper-catalyzed aerobic oxidative C-N coupling between 2-aminopyridine and terminal alkynes at room temperature via C[triple bond, length as m-dash]C triple bond cleavage is described. This reaction allows direct synthesis of biologically important pyridyl amides by utilization of commercially available starting materials without the need for bases/external oxidants.

Copper(I) chloride catalysed room temperature Csp–Csp homocoupling of terminal alkynes mediated by visible light

We developed a technique mediated by visible light for the aerobic homocoupling of terminal alkynes to synthesize 1,3-conjugated diynes using a copper(I) chloride catalyst at room temperature. Compared with previously reported thermal processes, this photochemical method is simple, uses only mild reaction conditions, produces high yields and works well for substrates with electron-withdrawing groups without the need for bases/ligands, oxidants or palladium catalysts.

Visible Light Copper Photoredox-Catalyzed Aerobic Oxidative Coupling of Phenols and Terminal Alkynes: Regioselective Synthesis of Functionalized Ketones via C≡C Triple Bond Cleavage

Direct oxidative coupling of phenols and terminal alkynes was achieved at room temperature by a visible-light-mediated copper-catalyzed photoredox process. This method allows regioselective synthesis of hydroxyl-functionalized aryl and alkyl ketones from simple phenols and phenylacetylene via C≡C triple bond cleavage. 47 examples were presented. From a synthetic perspective, this protocol offers an efficient synthetic route for the preparation of pharmaceutical drugs, such as pitofenone and fenofibrate.

Singlet oxygen-mediated selective C–H bond hydroperoxidation of ethereal hydrocarbons

Singlet O2 is a key reactive oxygen species responsible for photodynamic therapy and is generally recognized to be chemically reactive towards C=C double bonds. Herein, we report the hydroperoxidation/lactonization of α-ethereal C–H bonds by singlet O2 (1Δg) under exceptionally mild conditions, i.e., room temperature and ambient pressure, with modest to high yields (38~90%) and excellent site selectivity. Singlet O2 has been known for > 90 years, but was never reported to be able to react with weakly activated C–H bonds in saturated hydrocarbons. Theoretical calculations indicate that singlet O2 directly inserts into the α-ethereal C–H bond in one step with conservation of steric configuration in products. The current discovery of chemical reaction of singlet oxygen with weakly activated solvent C–H bonds, in addition to physical relaxation pathway, provides an important clue to a 35-year-old unresolved mystery regarding huge variations of solvent dependent lifetime of singlet O2.Singlet oxygen is known to react with carbon–carbon double bonds. Here, the authors show the unusual functionalization of α-ethereal C–H bonds mediated by singlet oxygen under mild conditions to afford lactones and hydroperoxide products.