The radicals of quercetin-derived antioxidants in Triton X-100 micelles.

We have employed photoionization with a pulsed laser (5 ns, 355 nm) as a direct access to the radicals of quercetin, five of its monoethers and three of its diethers in nonionic micelles. On a submicrosecond timescale, the first detectable intermediates are neutral radicals NRx, which can then be deprotonated to give radical anions RANxy, where x and y denote the phenoxyl positions bearing spin and/or charge. Alkylation at oxygen x blocks the formation of NRx and RANxy but barely changes the spectra of all other structurally possible radical isomers. Through systematic comparison, this allowed unambiguous radical identification and spectral assignment by experiment in all cases: NR3 is preferred over NR4', all other NRx are negligible; NR3 and NR4' are deprotonated at oxygens 4' and 3', respectively, unless barred by substitution, or at oxygen 7. As a caveat, B3LYP calculations on the radicals with a 6-311++g(2d,2p) basis set and a PCM solvation model gave only partially correct energy orderings and spectra, the former most likely due to an inability fully to describe the intramolecular hydrogen bonds and the latter possibly due to spin contamination. The favored deprotonation of NR3 is associated with a typical pKa of 4.8 and first-order kinetics, that of NR4' with a pKa of 3.9 and complex kinetics, suggesting NR3' as a fleeting intermediate. Both reverse reactions are diffusion controlled.

Do equilibrium and rate constants of intramicellar reactions depend on micelle size?

We have studied the combined static and dynamic quenching of pyrene by methyl viologen in sodium alkyl sulfate micelles varying in volume by a factor of more than 4. Size controls were the temperature T (283 K-333 K) and the alkyl chain length n (9-14) as well as, with n = 12 only, added NaCl (up to 9 times the surfactant weight-in concentration). At high [NaCl], up to 40% of the viologen resides in the aqueous bulk and quenches dynamically across the micelle-water interface with a rate limited by its diffusion-controlled attachment to the micelle. The micellar aggregation numbers depend linearly both on n and on the difference between T and the Krafft temperature; we have derived interpolation formulas for them as well as for the associated molar volumes of the micelles; the aggregation numbers at the critical micelle concentration are also linear functions of T, and the exponent relating them to the aggregation numbers at other concentrations is temperature independent. At given T, the volume-based quenching rate constants for different n or [NaCl] are very similar, and the same holds true for the equilibrium constants of the static quenching. Arrhenius plots identify the microviscosity inside the micelles as octanol-like; van't Hoff plots give virtually the same reaction enthalpies and entropies as in homogeneous methanolic solution; and the underlying kinetic and thermodynamic parameters are not modified by the micelle size.

Laser Access to Quercetin Radicals and Their Repair by Co-antioxidants.

We have demonstrated the feasibility and ease of producing quercetin radicals by photoionization with a pulsed 355 nm laser. A conversion efficiency into radicals of 0.4 is routinely achieved throughout the pH range investigated (pH 2-9), and the radical generation is completed within a few ns. No precursor other than the parent compound is needed, and the ionization by-products do not interfere with the further fate of the radicals. With this generation method, we have characterized the quercetin radicals and studied the kinetics of their repairs by co-antioxidants such as ascorbate and 4-aminophenol. Bell-shaped pH dependences of the observed rate constants reflect opposite trends in the availability of the reacting protonation forms of radical and co-antioxidant and even at their maxima mask the much higher true rate constants. Kinetic isotope effects identify the repairs as proton-coupled electron transfers. An examination of which co-antioxidants are capable of repairing the quercetin radicals and which are not confines the bond dissociation energies of quercetin and its monoanion experimentally to 75-77 kcal mol-1 and 72-75 kcal mol-1 , a much narrower interval in the case of the former than previously estimated by theoretical calculations.

Pyrene-viologen complexes in SDS micelles: quenching parameters and use as probes of aggregation numbers.

Through a formal-kinetic treatment, we rigorously derive the micellar occupations in the presence of fluorophore-quencher ground-state complexes and the resulting expressions for the time-dependent and stationary observables in the case of combined static and dynamic quenching. We present a protocol for data analysis that effectively isolates the processes, thereby ensuring rapid fit convergence and unique parameter sets. By this approach, we interpret time-resolved fluorescence measurements on pyrene quenched by a homologous series of viologens in SDS micelles. The dynamic intramicellar quenching is diffusion limited; and the formation of the ground-state complexes is entropy driven, with a constant increment per methylene group in the viologen sidechains. The micellar aggregation numbers are obtained with a precision comparable to neutron scattering, including their temperature dependence.

Laser-Induced Wurtz-Type Syntheses with a Metal-Free Photoredox Catalytic Source of Hydrated Electrons.

Upon irradiation with ns laser pulses at 355 nm, 2-aminoanthracene in SDS micelles readily produces hydrated electrons. These "super-reductants" rapidly attack substrates such as chloro-organics and convert them into carbon-centred radicals through dissociative electron transfer. For a catalytic cycle, the aminoanthracene needs to be restored from its photoionization by-product, the radical cation, by a sacrificial donor. The ascorbate monoanion can only achieve this across the micelle-water interface, but the monoanion of ascorbyl palmitate results in a fully micelle-contained regenerative electron source. The shielding by the micelle in the latter case not only increases the life of the catalyst but also strongly suppresses the interception of the carbon-centred radicals by the hydrogen-donating ascorbate moiety; and in conjunction with the high local concentrations effected by the pulsed laser, termination by radical dimerization thus dominates. We have obtained a complete and consistent picture through monitoring the individual steps and the assembled system by flash photolysis on fast and slow timescales, from microseconds to minutes; and in preparative studies on a variety of substrates, we have achieved up to quantitative dimerization with a turnover on the order of 1 mmol per hour.

Combined static and dynamic intramicellar fluorescence quenching: effects on stationary and time-resolved Stern-Volmer experiments.

We have conducted a theoretical and experimental study of Stern-Volmer experiments in micellar systems for the important case that fluorophore and quencher remain confined to their micelle during the luminescence decay (the "immobile probe/immobile quencher" scenario) and exhibit static quenching followed by dynamic quenching. By a comparative mathematical analysis, we have exposed inherent physical and mathematical contradictions of earlier theories. We present a general framework that allows a very simple derivation of consistent solutions. Even with the correct model, strong parameter correlations severely compromise fit uniqueness when the stationary luminescence is the only observable, but these correlations can be removed by parallel absorption measurements and do not occur in time-resolved luminescence experiments. The application of our protocol to pyrene quenching by substituted viologens in SDS micelles revealed a linear dependence of the apparent aggregation number of the surfactant on the equilibrium constant of formation of ground-state complexes, which can be quantitatively explained by a preference of the quencher for micelles containing the fluorophore. The complex formation is entropy controlled, as evidenced by a driving force that decreases linearly with the number of free rotors in the viologen sidechains.

First Micelle-Free Photoredox Catalytic Access to Hydrated Electrons for Syntheses and Remediations with a Visible LED or even Sunlight.

Hydrated electrons are super-reductants, yet can be generated with visible light when two photons are pooled, most efficiently through storing the energy of the first photon in a radical pair formed by the reduction of an excited catalyst by a sacrificial donor. All previous such systems for producing synthetically useable amounts of hydrated electrons with an LED in the visible range had to resort to compartmentalization by SDS micelles to curb the performance-limiting recombination of the pair. To overcome micelle-imposed constraints on sustainability and applications, we have instead attached carboxylate groups to a ruthenium (tris)bipyridyl catalyst such that its pentaanionic radical strongly repels the dianionic radical of the bioavailable donor urate. We have explored the influence of the Coulombic interactions on the electron generation by a time-resolved study from microseconds to hours, including for comparison the unsubstituted complex, which forms a monocationic radical, with and without SDS micelles. The new homogeneous electron source is best with regard to stability and total electron output; it has a broader synthetic scope because it does not entail micellar shielding of less hydrophilic compounds, which particularly facilitates cross-couplings; and it tolerates supramolecular containers as carriers of water-insoluble substrates or products. As an application in the field, we demonstrate the solar remediation of a recalcitrant chloro-organic bulk chemical.

Micellized Tris(bipyridine)ruthenium Catalysts Affording Preparative Amounts of Hydrated Electrons with a Green Light-Emitting Diode.

We have explored alkyl substitution of the ligands as a means to improve the performance of the title complexes in photoredox catalytic systems that produce synthetically useable amounts of hydrated electrons through photon pooling. Despite generating a super-reductant, these electron sources only consume the bioavailable ascorbate and are driven by a green light-emitting diode (LED). The substitutions influence the catalyst activity through the interplay of the quenching parameters, the recombination rate of the reduced catalyst OER and the ascorbyl radical across the micelle-water interface, and the quantum yield of OER photoionization. Laser flash photolysis yields comprehensive information on all these processes and allows quantitative predictions of the activity observed in LED kinetics, but the latter method provides the only access to the catalyst stability under illumination on the timescale of the syntheses. The homoleptic complex with dimethylbipyridine ligands emerges as the optimum that combines an activity twice as high with an undiminished stability in relation to the parent compound. With this complex, we have effected dehalogenations of alkyl and aryl chlorides and fluorides, hydrogenations of carbon-carbon double bonds, and self- as well as cross-coupling reactions. All the substrates employed are impervious to ordinary photoredox catalysts but present no problems to the hydrated electron as a super-reductant. A particularly attractive application is selective deuteration with high isotopic purity, which is achieved simply by using heavy water as the solvent.

A Green-LED Driven Source of Hydrated Electrons Characterized from Microseconds to Hours and Applied to Cross-Couplings.

We present a novel photoredox catalytic system that delivers synthetically usable concentrations of hydrated electrons when illuminated with a green light-emitting diode (LED). The catalyst is a ruthenium complex protected by an anionic micelle, and the urate dianion serves as a sacrificial donor confined to the aqueous bulk. By virtue of its chemical properties, this donor not only suppresses charge recombination that would limit the electron yield, but also enables this system to perform cross-couplings through the action of hydrated electrons, the first examples of which are reported here. We have investigated the kinetics of all the steps involving the electron and its direct precursor in a comparative study by means of laser flash photolysis and by monitoring product formation during LED photolysis. Despite the differences in timescales, each approach on its own already gives a complete picture of the reaction over a temporal range spanning ten orders of magnitude. Discrepancies between the kinetic parameters obtained with the two complementary techniques can be rationalized with the slow secondary chemistry of the system; they reveal that the product-based method provides a more accurate description because it also responds to the changes of the system composition during a synthesis; hence, they demonstrate that in complex systems the timescale of the experimental observation should be matched to that of the actual application.

Resveratrol Radical Repair by Vitamin†C at the Micelle-Water Interface: Unexpected Reaction Rates Explained by Ion-Dipole Interactions.

Repair reactions of lipophilic phenoxy radicals by hydrophilic co-antioxidants at model membranes are important for understanding the factors that govern the interactions between radical scavengers in biological systems. By using near-UV photoionization, we have selectively generated the phenoxy radical of the famous antioxidant resveratrol inside anionic (SDS), cationic (DTAC), or neutral (TX-100) micelles, as well as in homogeneous aqueous solution, and have compared its repairs in these media by the water-soluble co-antioxidants ascorbic acid and ascorbate monoanion. With all surfactants, these reactions are dynamic processes at the micelle-water interface. Whereas for the combinations ascorbate monoanion/ ionic micelle the repair rates can be rationalized by the Coulombic interactions, unexpected effects were observed with the neutral ascorbic acid and the charged micelles: for the anionic micelles, this repair is three times faster than in homogeneous solution, and two orders of magnitude faster than for the cationic micelles. Given that the repair by a concerted proton-electron transfer demands a coplanar arrangement of the resveratrol phenoxy centre sticking out into the Stern layer and the co-antioxidant hydroxy moiety approaching from the aqueous bulk, we explain these results by ion-dipole interactions: only at a negatively charged micellar surface does the direction of the large dipole moment of ascorbic acid lead to an orientation favourable for the repair.

Generating Hydrated Electrons for Chemical Syntheses by Using a Green Light-Emitting Diode (LED).

We present the first working system for accessing and utilizing laboratory-scale concentrations of hydrated electrons by photoredox catalysis with a green light-emitting diode (LED). Decisive are micellar compartmentalization and photon pooling in an intermediate that decays with second-order kinetics. The only consumable is the nontoxic and bioavailable vitamin C. A turnover number of 1380 shows the LED method to be on par with electron generation by high-power pulsed lasers, but at a fraction of the cost. The extreme reducing power of the electron and its long unquenched life as a ground-state species are synergistic. We demonstrate the applicability to the dechlorination, defluorination, and hydrogenation of compounds that are inert towards all other visible-light photoredox catalysts known to date. A comprehensive mechanistic investigation from microseconds to hours yields results of general validity for photoredox catalysis with photon pooling, allowing optimization and upscaling.

Laboratory-scale photoredox catalysis using hydrated electrons sustainably generated with a single green laser.

The ruthenium-tris-bipyridyl dication as catalyst combined with the ascorbate dianion as bioavailable sacrificial donor provides the first regenerative source of hydrated electrons for chemical syntheses on millimolar scales. This electron generator is operated simply by illumination with a frequency-doubled Nd:YAG laser (532 nm) running at its normal repetition rate. Much more detailed information than by product studies alone was obtained by photokinetical characterization from submicroseconds (time-resolved laser flash photolysis) up to one hour (preparative photolysis). The experiments on short timescales established a reaction mechanism more complex than previously thought, and proved the catalytic action by unchanged concentration traces of the key transients over a number of flashes so large that the accumulated electron total surpassed the catalyst concentration many times. Preparative photolyses revealed that the sacrificial donor greatly enhances the catalyst stability through quenching the initial metal-to-ligand charge-transfer state before destructive dd states can be populated from it, such that the efficiency of this electron generator is no longer limited by catalyst decomposition but by electron scavenging by the accumulating oxidation products of the ascorbate. Applications covered dechlorinations of selected aliphatic and aromatic chlorides and the reduction of a model ketone. All these substrates are impervious to photoredox catalysts exhibiting lower reducing power than the hydrated electron, but the combination of an extremely negative standard potential and a long unquenched life allowed turnover numbers up to 1400 with our method.

3-Aminoperylene and ascorbate in aqueous SDS, one green laser flash and action! Sustainably detoxifying a recalcitrant chloro-organic.

The hydrated electron represents a "super-reductant" in water, providing 2.9 eV of reductive power, which suffices to decompose nonactivated aliphatic halides. We show that 3-amino-perylene in SDS micelles, when combined with the bioavailable ascorbate as an extramicellar sacrificial donor, sustainably produces hydrated electrons through photoredox catalysis with green light, from a metal-free system, and at near-physiological pH. Photoionization of the amine with a 532 nm laser yields an extremely long-lived radical cation as the by-product, and a subsequent reaction of the latter with the sacrificial donor across the micelle/water interface regenerates the catalyst. The regeneration step involves parallel reactions between differently protonated forms, causing a bell-shaped pH dependence in basic medium. We have separated these processes kinetically. Employing this catalytic cycle for the laboratory-scale decomposition of chloroacetate, an accepted model compound for toxic and persistent halo-organic waste, gave turnover numbers of about 170. Even though both the substrate and the sacrificial donor compete for the hydrated electron, their consumption ratio is practically independent of the initial concentration ratio because the formal radical anion of the ascorbate undergoes secondary scavenging by the chloroacetate. In the course of the reaction, the initial hydrophobic catalyst is converted into a secondary species that is hydrophilic and still exhibits catalytic activity.

Combined static and dynamic quenching in micellar systems-closed-form integrated rate laws verified using a versatile probe.

We demonstrate that the 3-aminoperylene radical cation is a near-ideal probe for investigating kinetic and transport processes in SDS micellar systems. Its isolated generation by two-photon ionization at a wavelength where most quenchers are transparent (532 nm) is free from side reactions; no exit from the micelles is detectable on a millisecond timescale; and its unquenched lifetime is as long as 350 ms, thus allowing the study of quenching processes over a time frame spanning at least 7 orders of magnitude. The lipophilic antioxidant ascorbyl palmitate reconverts it to its parent compound through the interplay of static and fast dynamic intramicellar quenching as well as through subsequent slow intermicellar migration. Using this radical-cation probe, we have successfully validated closed-form expressions which we derived for the probe decay in all these situations. From these functions, we also obtained an exact and closed-form analytical result for Stern-Volmer experiments with combined static and dynamic intramicellar quenching.

Green-light ionization of 3-aminoperylene in SDS micelles-a promising access to hydrated electrons despite a myth debunked.

Using an improved methodology, we have carefully reinvestigated the title reaction by laser flash photolysis and disproved an earlier study (J. K. Thomas and P. Piciulo, J. Am. Chem. Soc., 1978, 100, 3239), which claimed this green-light ionization to be monophotonic, the only instance of such a scenario ever reported for a stable compound. We show it to be biphotonic instead, in accordance with thermodynamic considerations, and present a photokinetic model that accurately represents the intensity dependences throughout the whole excitation range in the green (532 nm) and the near UV (355 nm), up to near-quantitative electron release in the latter case. A major artifact deceptively similar to a chemical decay arises from an SDS-related laser-induced turbidity but can be eliminated by difference experiments or careful selection of excitation intensities and temporal windows. The ionization step is not accompanied by side processes, and affords an extremely long-lived (0.35 s) radical cation remaining solubilized. The micelles completely block attacks of hydrated electrons or hydroxyl radicals on the starting material and its radical cation but allow a post-ionization regeneration by high concentrations of the hydrophilic ascorbate monoanion.

Photoionization access to cyclodextrin-encapsulated resveratrol phenoxy radicals and their repair by ascorbate across the phase boundary.

Repair reactions of phenoxy radicals by co-antioxidants are key parts of radical scavenging cascades in nature. Yet, kinetic and mechanistic studies of such repairs are scarce, particularly at biologically relevant interfaces. For the popular red-wine polyphenol resveratrol, we present the first example of repairing a cyclodextrin-complexed phenoxy radical by a water soluble co-antioxidant (ascorbate), a reaction of practical importance given the fact that both antioxidants and cyclodextrins are large-scale food additives. To prepare the phenoxy radical from its parent compound inside the cavities of native or hydroxypropyl-substituted α- and ß-cyclodextrins, we employed laser photoionization with UV-A (355 nm), which does not rely on additional reagents, and therefore leaves the repair completely undisturbed. A global fit of the intensity dependence pinpoints the cyclodextrin influences on the biphotonic resveratrol ionization as a shift of the ground-state absorption spectrum and a longer life of the first excited state due to the suppression of the geometrical isomerization by the rigid containers, whereas the actual electron ejection from an upper excited state is almost medium-independent. The exchange of the phenoxy radical between the cyclodextrin interior and the aqueous bulk is immeasurably slow on the timescale of its repair by the ascorbate monoanion. Kinetic H/D isotope effects and activation entropies identify the repair at the cyclodextrin-water interface as a concerted proton-electron transfer with no mechanistic difference to homogeneous aqueous solution. The activation enthalpies reveal a steric repulsion between ascorbate and cyclodextrin that indicates a deeper embedding of the less hydrophilic phenoxy radical in the macrocycle compared to the parent compound, with the observed structure-rate relationships explainable on the basis of the cavity diameter and depth.

Combining energy and electron transfer in a supramolecular environment for the "green" generation and utilization of hydrated electrons through photoredox catalysis.

We present a new mechanism that sustainably produces hydrated electrons, i.e., extremely strong reductants, yet consumes only green photons (532 nm) and the bioavailable ascorbate as sacrificial donor. The mechanism couples an energy-transfer cycle, in which a light-harvesting ruthenium polypyridine complex absorbs a first photon and passes the excitation energy on to a pyrene-based redox catalyst, with an electron-transfer cycle, in which the resulting triplet is reductively quenched and the energy-rich aryl radical anion is finally ionized by a second photon. Thus separating the roles of primary and secondary absorber permitted choosing a redox catalyst with a nonabsorbing ground state but efficiently ionizable radical anion; the quantum yield of the ionization step in our complex mechanism surpasses that in a simple photoredox cycle featuring only the metal complex by a factor of four. We suppressed undesired cross reactions through the noncovalent interactions of an anionic micelle with the charges of the reactants, intermediates, and products: the cationic light-harvesting complex remains affixed to the micelle surface, which blocks the access of the negatively charged sacrificial donor, aryl radical anion and hydrated electron, but allows the pyrene ground-state almost unhindered entry into the Stern layer despite a carboxylate substituent by virtue of its large dipole moment. We demonstrate the applicability of the mechanism to the reductive detoxification of halogenated organic waste, which hitherto required UV-C for electron generation, by decomposing the typical model compound chloroacetate.

A new approach to elucidating repair reactions of resveratrol.

The repair by co-antioxidants of the phenoxy radical of resveratrol, the famous health-preserving ingredient of red wine, is a key step of radical scavenging cascades in nature. To generate that radical, we employed 355 nm photoionization as a direct and selective access that reduces the chemical complexity and is equally applicable in organized phases; to monitor it, we used its hitherto unreported absorption in the red where no other species in our systems interfere. With this novel approach, we measured rate constants and H/D kinetic isotope effects for the repairs by ascorbate, trolox (a vitamin E analogue) and 4-aminophenol, and identified the mechanisms as one-step hydrogen abstractions. Cysteine and glutathione are unreactive. In micellar solution (SDS), the repair by ascorbate is much slower and involves only the hydrophilic phenoxy moieties protruding from the micelles. The new experimental strategy also led to a reevaluation of extinction coefficients, rate constants and mechanisms.

Generating hydrated electrons through photoredox catalysis with 9-anthrolate.

Hydrated electrons are among the strongest reductants known. Adding the ascorbate dianion as a sacrificial donor turns the photoionization of 9-anthrolate in water into a catalytic cycle for their in situ production with near-UV light (355 nm). The photoionization step is exclusively biphotonic and occurs via the first excited singlet state of the catalyst. Neither triplet formation nor any photochemical side reactions interfere. The ionization by-product, the anthroxy radical, is inert towards the ascorbate monoanion but is rapidly reduced by the dianion, thereby recovering the starting catalyst. A sufficient amount of the sacrificial donor makes that reduction quantitative and leads to a sustainable generation of hydrated electrons, as is evidenced by electron yields greatly surpassing the catalyst concentration. Control experiments established that the superincrease is indeed due to the catalyst regeneration and not to an ionization of other species involved in the reaction.

Highly efficient green-light ionization of an aryl radical anion: key step in a catalytic cycle of electron formation.

A sustainable generation of hydrated electrons with green light would allow solar-driven applications of this potent reductant, such as the detoxification of halogenated organic waste. Using two-color laser flash photolysis, we have studied the photoionizations of the 1,5-naphthalene disulfonate radical anion and triplet with 532 nm as well as 355 nm. The radical anion is prepared by reducing the triplet with the bioavailable ascorbate monoanion under physiological conditions; its photoionization recovers the starting substrate, so turns the reaction sequence into a catalytic cycle. A comparison of the four ionizations suggests that their efficiency is strongly influenced by the electronic configuration of the state ejecting the electron. The quantum yield for ionizing the radical anion with 532 nm (0.27) is at least four times higher than for the very few known examples of such green-light ionizations and comparable to the most efficient UV ionizations known to date, so this system might represent a breakthrough towards the "green" production of hydrated electrons.