Photooxidative Coupling of Thiophenol Derivatives to Disulfides

Abstract

Disulfide bonds play an important role in determining the structure and stability of proteins and nanoparticles. Despite extensive studies on the oxidation of thiols for the synthesis of disulfides, little is known about the photooxidation of thiols, which may be a clean, safe, and economical alternative to the use of harmful and expensive metal-containing oxidants and catalysts. In this paper, we report the photooxidative coupling of thiophenol derivatives to disulfides. Para-substituted thiophenol derivatives, p-SHC(6)H(4)X (X = NO(2), COOH, Cl, and OCH(3)), are irradiated, and disulfides, X(2)(C(6)H(4))(2)S(2), are identified as the major photoproducts using Raman, UV-vis, IR, and NMR spectroscopies. For p-nitrothiophenol (pNTP), 4,4'-dinitrodiphenyldisulfide (DNDPDS) is produced in 81% yield. The product yield changes with pH, being the highest at pH ≈ 5, suggesting that both neutral thiol and anionic thiolate forms of pNTP are required for the photoreaction to occur. Excitation at 455 nm, at which the thiolate form of pNTP absorbs strongly, leads to the largest yield of DNDPDS, whereas very little DNDPDS is formed by excitation of the thiol form of pNTP at 325 nm. Our observations suggest that the photooxidation occurs via collisions of the electronically excited thiolate form of pNTP with the surrounding neutral thiol forms of pNTP. The photooxidation reaction happens regardless of the electron-withdrawing or electron-donating properties of the substituents if the pH and excitation wavelengths are properly chosen. The versatility of light and generality of the photooxidative coupling reaction of thiophenol derivatives may open new possibilities for selective and site-specific photocontrol of disulfide bond formation in biology and nanomaterial science as well as in synthetic chemistry.

Mechanistic Insights into the Interface‐Directed Transformation of Thiols into Disulfides and Molecular Hydrogen by Visible‐Light Irradiation of Quantum Dots

“…Received: November 26, 2013 Published online: January 27,2014 . Keywords: disulfides · photocatalysis · quantum dots · radical reactions · thiols…”

Batch and Flow Synthesis of Disulfides by Visible‐Light‐Induced TiO2 Photocatalysis

“…Upon light irradiation, 33 %o ft he target disulfide (2)w as observed (Table 1, entries 3and 4). It should be noted that photooxidative disulfide formationi sp ossible in the presence of ab ase under visible light irradiation in the absence of any photocatalyst as shown by Yoon and coworkers [18] However, the transformation has av ery narrow scope and is limitedt o those thiols of which the correspondingt hiolate absorbsint he visible light region, for example, p-NO2-thiophenol. Improved results were obtained when the light source was switched from compact fluorescent light (CFL) to white light emitting diodes (LEDs;T able 1, entries 5-7).…”

“…Next, we examined the photocatalytic intramolecular disulfide transformation on am ore challenging peptide (18), the reduced form of the yeast-derived C-terminal lipid-bindingm otif of the TOR1 (target of rapamycin) FATC domain (y1fatc). [28] Interestingly,t he redox state of the peptide regulates the membrane bindingp roperties of the protein, with the oxidized disulfide form binding to lipid membranes more tightly than the reducedf orm.…”

Vis/NIR light driven mild and clean synthesis of disulfides in the presence of Cu2(OH)PO4 under aerobic conditions

“…Disulfide bonds play a major role in determining the structure and stability of protein. 8 Interstrand disulfide bond between Cys residues can stabilize the parallel β-sheet secondary structure. 9 Cyclic disulfide-rich peptides have exceptional stability and are promising frameworks for drug design.…”