Probing the Transition State-to-Intermediate Continuum: Mechanistic Distinction between a Dry versus Wet Perepoxide in the Singlet Oxygen "Ene" Reaction at the Air-Water Interface.

A mechanistic study is reported for the reactions of singlet oxygen (1O2) with alkene surfactants of tunable properties. Singlet oxygen was generated either top-down (photochemically) by delivery as a gas to an air-water interface or bottom-up (chemically) by transport to the air-water interface as a solvated species. In both cases, reactions were carried out in the presence of 7-carbon (7C), 9-carbon (9C), or 11-carbon (11C) prenylsurfactants [(CH3)2C═CH(CH2)nSO3- Na+ (n = 4, 6, 8)]. Higher "ene" hydroperoxide regioselectivities (secondary ROOH 2 to tertiary ROOH 3) were reached in delivering 1O2 top-down through air as compared to bottom-up via aqueous solution. In the photochemical reaction, ratios of 2:3 increased from 2.5:1 for 7C, to 2.8:1 for 9C, and to 3.2:1 for 11C. In contrast, in the bubbling system that generated 1O2 chemically, the selectivity was all but lost, ranging only from 1.3:1 to 1:1. The phase-dependent regioselectivities appear to be correlated with the "ene" reaction with photochemically generated, drier 1O2 at the air-water interface vs those with wetter 1O2 from the bubbling reactor. Density functional theory-calculated reaction potential energy surfaces (PESs) were used to help rationalize the reaction phase dependence. The reactions in the gas phase are mediated by perepoxide transition states with 32-41 kJ/mol binding energy for C═C(π)···1O2. The perepoxide species, however, evolve to well-defined stationary structures in the aqueous phase, with covalent C-O bonds and 85-88 kJ/mol binding energy. The combined experimental and computational evidence points to a unique mechanism for 1O2 "ene" tunability in a perepoxide continuum from a transition state to an intermediate.

Alkane Chain-extended Pterin Through a Pendent Carboxylic Acid Acts as Triple Functioning Fluorophore, 1 O2 Sensitizer and Membrane Binder.

In order to develop a new long alkane chain pterin that leaves the pterin core largely unperturbed, we synthesized and photochemically characterized decyl pterin-6-carboxyl ester (CapC) that preserves the pterin amide group. CapC contains a decyl-chain at the carboxylic acid position and a condensed DMF molecule at the N2 position. Occupation of the long alkane chain on the pendent carboxylic acid group retains the acid-base equilibrium of the pterin headgroup due to its somewhat remote location. This new CapC compound has relatively high fluorescence emission and singlet oxygen quantum yields attributed to the lack of through-bond interaction between the long alkane chain and the pterin headgroup. The calculated lipophilicity is higher for CapC compared to parent pterin and pterin-6-carboxylic acid (Cap) and comparable to previously reported O- and N-decyl-pterin derivatives. CapC's binding constant Kb (8000 M-1 in L-α-phosphatidylcholine from egg yolk) and ΦF :Φ∆ ratio (0.26:0.40) point to a unique triple function compound, although the hydrolytic stability of CapC is modest due to its ester conjugation. CapC is capable of the general triple action not only as a membrane intercalator, but also fluorophore and 1 O2 sensitizer, leading to a "self-monitoring" membrane fluorescent probe and a membrane photodamaging agent.

Dark-Binding Process Relevant to Preventing Photosensitized Oxidation: Conformation-Dependent Light and Dark Mechanisms by a Dual-Functioning Diketone.

Few photosensitizers function in both light and dark processes as they usually have no function when the lights are turned off. We hypothesized that light and dark mechanisms in an α-diketone will be decoupled by dihedral rotation in a conformation-dependent binding process. Successful decoupling of these two functions is now shown. Namely, anti- and syn-skewed conformations of 4,4'-dimethylbenzil promote photosensitized alkoxy radical production, whereas the syn conformation promotes a binding shutoff reaction with trimethyl phosphite. Less rotation of the diketone is better suited to the photosensitizing function since phosphite binding arises through the syn conformer of lower stability. The dual function seen here with the α-diketone is generally not available to sensitizers of limited conformational flexibility, such as porphyrins, phthalocyanines, and fullerenes.

S,S-Chiral Linker Induced U Shape with a Syn-facial Sensitizer and Photocleavable Ethene Group.

There is a major need for light-activated materials for the release of sensitizers and drugs. Considering the success of chiral columns for the separation of enantiomer drugs, we synthesized an S,S-chiral linker system covalently attached to silica with a sensitizer ethene near the silica surface. First, the silica surface was modified to be aromatic rich, by replacing 70% of the surface groups with (3-phenoxypropyl)silane. We then synthesized a 3-component conjugate [chlorin sensitizer, S,S-chiral cyclohexane and ethene building blocks] in 5 steps with a 13% yield, and covalently bound the conjugate to the (3-phenoxypropyl)silane-coated silica surface. We hypothesized that the chiral linker would increase exposure of the ethene site for enhanced 1 O2 -based sensitizer release. However, the chiral linker caused the sensitizer conjugate to adopt a U shape due to favored 1,2-diaxial substituent orientation; resulting in a reduced efficiency of surface loading. Further accentuating the U shape was π-π stacking between the (3-phenoxypropyl)silane and sensitizer. Semiempirical calculations and singlet oxygen luminescence data provided deeper insight into the sensitizer's orientation and release. This study has lead to insight on modifications of surfaces for drug photorelease and can help lead to the development of miniaturized photodynamic devices.

Kinetic Control in the Regioselective Alkylation of Pterin Sensitizers: A Synthetic, Photochemical, and Theoretical Study.

Alkylation patterns and excited-state properties of pterins were examined both experimentally and theoretically. 2D NMR spectroscopy was used to characterize the pterin derivatives, revealing undoubtedly that the decyl chains were coupled to either the O4 or N3 sites on the pterin. At a temperature of 70°C, the pterin alkylation regioselectively favored the O4 over the N3. The O4 was also favored when using solvents, in which the reactants had increased solubility, namely N,N-dimethylformamide and N,N-dimethylacetamide, rather than solvents in which the reactants had very low solubility (tetrahydrofuran and dichloromethane). Density functional theory (DFT) computed enthalpies correlate to regioselectivity being kinetically driven because the less stable O-isomer forms in higher yield than the more stable N-isomer. Once formed these compounds did not interconvert thermally or undergo a unimolecular "walk" rearrangement. Mechanistic rationale for the factors underlying the regioselective alkylation of pterins is suggested, where kinetic rather than thermodynamic factors are key in the higher yield of the O-isomer. Computations also predicted greater solubility and reduced triplet state energetics thereby improving the properties of the alkylated pterins as 1 O2 sensitizers. Insight on thermal and photostability of the alkylated pterins is also provided.

Lipophilic Decyl Chain-Pterin Conjugates with Sensitizer Properties.

A new series of decyl chain [-(CH2)9CH3] pterin conjugates have been investigated by photochemical and photophysical methods, and with theoretical solubility calculations. To synthesize the pterins, a nucleophilic substitution (SN2) reaction was used for the regioselective coupling of the alkyl chain to the O site over the N3 site. However, the O-alkylated pterin converts to N3-alkylated pterin under basic conditions, pointing to a kinetic product in the former and a thermodynamic product in the latter. Two additional adducts were also obtained from an N-amine condensation of DMF solvent molecule as byproducts. In comparison to the natural product pterin, the alkyl chain pterins possess reduced fluorescence quantum yields (ΦF) and increased singlet oxygen quantum yields (ΦΔ). It is shown that the DMF-condensed pterins were more photostable compared to the N3- and O-alkylated pterins bearing a free amine group. The alkyl chain pterins efficiently intercalate in large unilamellar vesicles, which is a good indicator of their potential use as photosensitizers in biomembranes. Our study serves as a starting point where the synthesis can be expanded to produce a wider series of lipophilic, photooxidatively active pterins.

"Ene" Reactions of Singlet Oxygen at the Air-Water Interface.

Prenylsurfactants [(CH3)2C═CH(CH2)nSO3(-) Na(+) (n = 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 (1)O2) is delivered as a gas.

Photoactive chitosan: a step toward a green strategy for pollutant degradation.

This article is a highlight of the paper by Ferrari et al. in this issue of Photochemistry and Photobiology. It describes the innovative use of rose bengal-conjugated chitosan as a reusable green catalyst that photo-degrades phenolic compounds in aqueous media, and thereby has decontamination potential of polluted waters. Whether a next-generation photoactive polymer that produces singlet oxygen is a solution to pollutant degradation can be argued. It is as yet unclear what polymeric sensitizer would be practical on a large scale. Nonetheless pursuing this goal is worthwhile.