“Ene” Reactions of Singlet Oxygen at the Air–Water Interface

Prenylsurfactants [(CH₃)₂CCH­(CH₂)_<i>n</i>SO₃^– Na⁺ (<i>n</i> = 4, 6, or 8)] were designed to probe the “ene” reaction mechanism of singlet oxygen at the air–water interface. Increasing the number of carbon atoms in the hydrophobic chain caused an increase in the regioselectivity for a secondary rather than tertiary surfactant hydroperoxide, arguing for an orthogonal alkene on water. The use of water, deuterium oxide, and H₂O/D₂O mixtures helped to distinguish mechanistic alternatives to homogeneous solution conditions that include dewetting of the π bond and an unsymmetrical perepoxide transition state in the hydroperoxide-forming step. The prenylsurfactants and a photoreactor technique allowed a certain degree of interfacial control of the hydroperoxidation reaction on a liquid support, where the oxidant (airborne ¹O₂) is delivered as a gas

Mechanism of Photochemical O‑Atom Exchange in Nitrosamines with Molecular Oxygen

The detection of an oxygen-atom photoexchange process of <i>N-</i>nitrosamines is reported. The photolysis of four nitrosamines (<i>N</i>-nitrosodiphenylamine <b>1</b>, <i>N</i>-nitroso-<i>N</i>-methylaniline <b>2</b>, <i>N</i>-butyl-<i>N</i>-(4-hydroxy­butyl)­nitrosamine <b>3</b>, and <i>N</i>-nitroso­diethylamine <b>4</b>) with ultraviolet light was examined in an ¹⁸O₂-enriched atmosphere in solution. HPLC/MS and HPLC-MS/MS data show that ¹⁸O-labeled nitrosamines were generated for <b>1</b> and <b>2</b>. In contrast, nitrosamines <b>3</b> and <b>4</b> do not exchange the ¹⁸O label and instead decomposed to amines and/or imines under the conditions. For <b>1</b> and <b>2</b>, the ¹⁸O atom was found not to be introduced by moisture or by singlet oxygen [¹⁸(¹O₂ ¹Δ_g)] produced thermally by ¹⁸O–¹⁸O labeled endoperoxide of <i>N,N</i>′-di­(2,3-hydroxy­propyl)-1,4-naphthalene dipropanamide (DHPN¹⁸O₂) or by visible-light sensitization. A density functional theory study of the structures and energetics of peroxy intermediates arising from reaction of nitrosamines with O₂ is also presented. A reversible head-to-tail dimerization of the <i>O-</i>nitrooxide to the 1,2,3,5,6,7-hexaoxa­diazocane (30 kcal/mol barrier) with extrusion of O¹⁸O accounts for exchange of the oxygen atom label. The unimolecular cyclization of <i>O-</i>nitrooxide to 1,2,3,4-trioxazetidine (46 kcal/mol barrier) followed by a retro [2 + 2] reaction is an alternative, but higher energy process. Both pathways would require the photoexcitation of the nitrooxide

Superhydrophobic Photosensitizers: Airborne ¹O₂ Killing of an in Vitro Oral Biofilm at the Plastron Interface

Singlet oxygen is a potent agent for the selective killing of a wide range of harmful cells; however, current delivery methods pose significant obstacles to its widespread use as a treatment agent. Limitations include the need for photosensitizer proximity to tissue because of the short (3.5 μs) lifetime of singlet oxygen in contact with water; the strong optical absorption of the photosensitizer, which limits the penetration depth; and hypoxic environments that restrict the concentration of available oxygen. In this article, we describe a novel superhydrophobic singlet oxygen delivery device for the selective inactivation of bacterial biofilms. The device addresses the current limitations by: immobilizing photosensitizer molecules onto inert silica particles; embedding the photosensitizer-containing particles into the plastron (i.e. the fluid-free space within a superhydrophobic surface between the solid substrate and fluid layer); distributing the particles along an optically transparent substrate such that they can be uniformly illuminated; enabling the penetration of oxygen via the contiguous vapor space defined by the plastron; and stabilizing the superhydrophobic state while avoiding the direct contact of the sensitizer to biomaterials. In this way, singlet oxygen generated on the sensitizer-containing particles can diffuse across the plastron and kill bacteria even deep within the hypoxic periodontal pockets. For the first time, we demonstrate complete biofilm inactivation (>5 log killing) of Porphyromonas gingivalis, a bacterium implicated in periodontal disease using the superhydrophobic singlet oxygen delivery device. The biofilms were cultured on hydroxyapatite disks and exposed to active and control surfaces to assess the killing efficiency as monitored by colony counting and confocal microscopy. Two sensitizer particle types, a silicon phthalocyanine sol–gel and a chlorin e6 derivative covalently bound to fluorinated silica, were evaluated; the biofilm killing efficiency was found to correlate with the amount of singlet oxygen detected in separate trapping studies. Finally, we discuss the applications of such devices in the treatment of periodontitis