Transient Radical Research Articles

Synergistic dynamics of photoionization and photoinduced electron transfer probed by laser flash photolysis and ultrafast fluorescence spectroscopy.

Photoionization (PI) and photoinduced electron transfer (PET) dynamics of coumarin 450 (C450) in micelles were investigated in the time domains of micro to femtoseconds using steady-state and time-resolved absorption and fluorescence spectroscopy. The PI of C450 occurs inside the micelles leads to the formation of C450 cation radical (CR) and hydrated electron, which is characterized by the respective transient absorption. The PI of C450 is monophotonic in nature and the yield is dependent on the charge of the micelles. The observation of amine CR in the transient absorption confirms the PET from amine to the excited state of C450 in micelles, which results in the quenching of both fluorescence intensity and lifetime. The decrease in femtosecond fluorescent decay of C450 and the absence of transient C450 radical anion in the presence of amine implies that the concerted ultrafast PET promoted PI and PET to the C450 CR-electron pair. The decrease in the time constant for the formation of relaxed state in the presence of amines is due to the ultrafast PET to the C450 CR-electron pair, which prevents the formation of a relaxed state through recombination at a longer time scale. In the present investigation, the recombination dynamics of the CR-electron pair is justified as one of the origins of the slow solvation in micelles. The influence of amine concentration on the decay of C450 CR indicates ET reaction between C450 CR and amine, which is further confirmed by the bleach recovery of C450 ground state in the presence of amine.

Radical 1,4-Aryl Migration Enabled Remote Cross-Electrophile Coupling of α-Amino-β-Bromo Acid Esters with Aryl Bromides.

We report an unprecedented, efficient nickel-catalysed radical relay for the remote cross-electrophile coupling of β-bromo-α-benzylamino acid esters with aryl bromides via 1,4-aryl migration/arylation cascades. β-Bromo-α-benzylamino acid esters are considered as unique molecular scaffolds allowing for aryl migration reactions, which are conceptually novel variants for the radical Truce-Smiles rearrangement. This reaction enables the formation of two new C(sp3 )-C(sp2 ) bonds using a bench-stable Ni/bipyridine/Zn system featuring a broad substrate scope and excellent diastereoselectivity, which provides an effective platform for the remote aryl group migration and arylation of amino acid esters via redox-neutral C(sp3 )-C(sp2 ) bond cleavage. Mechanistically, this cascade reaction is accomplished by combining two powerful catalytic cycles consisting of a cross-electrophile coupling and radical 1,4-aryl migration through the generation of C(sp3 )-centred radical intermediates from the homolysis of C(sp3 )-Br bonds and the switching of the transient alkyl radical into a robust α-aminoalkyl radical.

Radical 1,4‐Aryl Migration Enabled Remote Cross‐Electrophile Coupling of α‐Amino‐β‐Bromo Acid Esters with Aryl Bromides

AbstractWe report an unprecedented, efficient nickel‐catalysed radical relay for the remote cross‐electrophile coupling of β‐bromo‐α‐benzylamino acid esters with aryl bromides via 1,4‐aryl migration/arylation cascades. β‐Bromo‐α‐benzylamino acid esters are considered as unique molecular scaffolds allowing for aryl migration reactions, which are conceptually novel variants for the radical Truce–Smiles rearrangement. This reaction enables the formation of two new C(sp3)−C(sp2) bonds using a bench‐stable Ni/bipyridine/Zn system featuring a broad substrate scope and excellent diastereoselectivity, which provides an effective platform for the remote aryl group migration and arylation of amino acid esters via redox‐neutral C(sp3)−C(sp2) bond cleavage. Mechanistically, this cascade reaction is accomplished by combining two powerful catalytic cycles consisting of a cross‐electrophile coupling and radical 1,4‐aryl migration through the generation of C(sp3)‐centred radical intermediates from the homolysis of C(sp3)−Br bonds and the switching of the transient alkyl radical into a robust α‐aminoalkyl radical.

Visible-Light-Induced Dearomatization of Indoles/Pyrroles with Vinylcyclopropanes: Expedient Synthesis of Structurally Diverse Polycyclic Indolines/Pyrrolines

Visible-light-induced cycloaddition reactions initiated via energy-transfer processes have recently evolved as powerful methods for the construction of strained cyclic molecules that are not easily accessed using known ground-state synthetic methods. Particularly, the reactions initiated by the excitation of aromatic rings provide an alternative solution to the direct transformations of aromatic feedstocks under the scheme of dearomatization. Vinylcyclopropanes (VCPs) are well-known reagents in radical clock experiments, working as a probe to detect transient radical intermediates. However, the synthetic applications in this regard still remain limited due to uncontrollable selectivities. Herein, we report visible-light-induced dearomatization of indole- or pyrrole-tethered VCPs, in which several competitive reaction pathways, including [5 + 2], [2 + 2], interrupted [5 + 2], and [5 + 4] cycloadditions, can be well regulated by engineering substrate structures and tuning reaction conditions. The reaction mechanism has been explored by combined experimental and computational investigations. These reactions provide a convenient method to synthesize structurally diverse polycyclic molecules with high efficiency and good selectivity.

Origin of sonocatalytic activity of fluorescent carbon dots

Although ultrasound-induced reactive oxygen species (ROS) have believed to be primary intermediates for the realization of sonodynamic therapy and sonocatalytic reactions, the mechanism of ROS production under ultrasound has not been well clarified till now. Here we discovered that ultrasound cavitation can break up oxygen-containing groups on the surface of carbon dots (CDs) to generate ROS, giving rise to a novel mechanism different from as-reported those. The bond cleavage of oxygen-containing groups contribute transient oxygen free radicals (•O−) that involve in the subsequent formation of ROS by quickly reacting with hydrogen ions and water, thereby leading to a twice higher sonocatalytic activity of CDs than TiO2. Moreover, the sonosensitizer function of CDs can be tuned by pH values of the surrounding environment that determine the generation and evolution reaction of oxygen free radicals under ultrasound irradiation. This finding paves a new way to design multifunctional sonosensitizers and utilize them in various fields.

1,3-Alkyl Transposition in Allylic Alcohols Enabled by Proton-Coupled Electron Transfer.

A method is described for the isomerization of acyclic allylic alcohols into β-functionalized ketones via 1,3-alkyl transposition. This reaction proceeds via light-driven proton-coupled electron transfer (PCET) activation of the O-H bond in the allylic alcohol substrate, followed by C-C β-scission of the resulting alkoxy radical. The transient alkyl radical and enone acceptor generated in the scission event subsequently recombine via radical conjugate addition to deliver β-functionalized ketone products. A variety of allylic alcohol substrates bearing alkyl and acyl migratory groups were successfully accommodated. Insights from mechanistic studies led to a modified reaction protocol that improves reaction performance for challenging substrates.

1,3‐Alkyl Transposition in Allylic Alcohols Enabled by Proton‐Coupled Electron Transfer

AbstractA method is described for the isomerization of acyclic allylic alcohols into β‐functionalized ketones via 1,3‐alkyl transposition. This reaction proceeds via light‐driven proton‐coupled electron transfer (PCET) activation of the O−H bond in the allylic alcohol substrate, followed by C−C β‐scission of the resulting alkoxy radical. The transient alkyl radical and enone acceptor generated in the scission event subsequently recombine via radical conjugate addition to deliver β‐functionalized ketone products. A variety of allylic alcohol substrates bearing alkyl and acyl migratory groups were successfully accommodated. Insights from mechanistic studies led to a modified reaction protocol that improves reaction performance for challenging substrates.

A Novel Stoichio-Kinetic Model for the DPPH• Assay: The Importance of the Side Reaction and Application to Complex Mixtures.

The 2,2-diphenyl-1-picrylhydrazyl (DPPH•) assay is widely used to determine the antioxidant activity of food products and extracts. However, the common DPPH• protocol uses a two-point measurement and does not give information about the kinetics of the reaction. A novel stoichio-kinetic model applied in this study monitors the consumption of DPPH• by common antioxidants following the second order reaction. The fitting of such decay yields the rate constant k1, which describes the main reaction between antioxidants and DPPH•, and the rate constant k2, which is attributed to a slower side reaction considering the products generated between the transient radicals (AO•) and another molecule of DPPH•. The model was first applied to antioxidant standards. Sinapic acid, Trolox and ascorbic and chlorogenic acids did not show any side reaction. Instead gallic, ferulic and caffeic acids achieved the best fitting with k2. The products of the side reaction for these compounds were confirmed and identified with high-resolution mass spectrometry. Finally, the kinetic model was applied to evaluate the antioxidant activity of eight herbal extracts. This study suggests a new kinetic approach to standardize the common DPPH• assay for the determination of antioxidant activity.

Cover Feature: Exploiting Transient Radical Cations as Brønsted Acids for Allylic C–H Heteroarylation of Enol Silyl Ethers (Chem. Eur. J. 36/2021)

The reaction pathways of transient radical species are difficult to control, like the soap bubbles in the wind depicted in the cover image. Yet, these short-lived intermediates, when one encounters another, readily assemble into a united structure, as two bubbles fuse into a bigger single bubble. The enol silyl ether-derived radical cations with a highly acidic allylic proton facilitates the single-electron reduction of cyanopyridines via protonation. The resulting two radical intermediates successively engage in the radical−radical coupling to produce heteroarylated enol silyl ethers. More information can be found in the Communication by T. Ooi et al. (DOI: 10.1002/chem.202101352).

Exploiting Transient Radical Cations as Brønsted Acids for Allylic C-H Heteroarylation of Enol Silyl Ethers.

Intermediary radical cations, generated through single-electron oxidation of enol silyl ethers by excited Ir-based photocatalysts, can be exploited as Brønsted acids for the activation of heteroarylcyanides. This strategy enables the direct allylic C-H heteroarylation of enol silyl ethers under visible-light irradiation.

Retraction Note: Endoperoxide formation by an α-ketoglutarate-dependent mononuclear non-haem iron enzyme.

The X-ray crystal structures of FtmOx1, the first known α-ketoglutarate-dependent mononuclear non-haem iron enzyme that can catalyse an endoperoxide formation reaction, are presented, along with further biochemical analyses which reveal the catalytic versatility of mononuclear non-haem iron enzymes, and help to unravel the mechanisms of endoperoxide biosyntheses. Verruculogen, a non-ribosomal peptide produced by various Aspergillus and Penicillium strains, contains an unusual and highly reactive endoperoxide (R-O-O-R) functional group that is generated from fumitremorgin B by the mononuclear non-haem iron enzyme FtmOx1. Pinghua Liu and colleagues report the X-ray crystal structures of FtmOx1 alone and in the presence of fumitremorgen B or α-ketoglutarate. Together with further biochemical analyses, these structures reveal the catalytic versatility of mononuclear non-haem iron enzymes, and help to unravel the mechanisms of endoperoxide biosyntheses. Verruculogen, a non-ribosomal peptide produced by various Aspergillus and Penicillium strains, contains an unusual and highly reactive endoperoxide (R-O-O-R) functional group that is generated from fumitremorgin B by the mononuclear non-haem iron enzyme FtmOx1. Pinghua Liu and colleagues report the X-ray crystal structures of FtmOx1 alone and in the presence of fumitremorgen B or α-ketoglutarate. Together with further biochemical analyses, these structures reveal the catalytic versatility of mononuclear non-haem iron enzymes, and help to unravel the mechanisms of endoperoxide biosyntheses. Many peroxy-containing secondary metabolites1,2 have been isolated and shown to provide beneficial effects to human health3,4,5. Yet, the mechanisms of most endoperoxide biosyntheses are not well understood. Although endoperoxides have been suggested as key reaction intermediates in several cases6,7,8, the only well-characterized endoperoxide biosynthetic enzyme is prostaglandin H synthase, a haem-containing enzyme9. Fumitremorgin B endoperoxidase (FtmOx1) from Aspergillus fumigatus is the first reported α-ketoglutarate-dependent mononuclear non-haem iron enzyme that can catalyse an endoperoxide formation reaction10,11,12. To elucidate the mechanistic details for this unique chemical transformation, we report the X-ray crystal structures of FtmOx1 and the binary complexes it forms with either the co-substrate (α-ketoglutarate) or the substrate (fumitremorgin B). Uniquely, after α-ketoglutarate has bound to the mononuclear iron centre in a bidentate fashion, the remaining open site for oxygen binding and activation is shielded from the substrate or the solvent by a tyrosine residue (Y224). Upon replacing Y224 with alanine or phenylalanine, the FtmOx1 catalysis diverts from endoperoxide formation to the more commonly observed hydroxylation. Subsequent characterizations by a combination of stopped-flow optical absorption spectroscopy and freeze-quench electron paramagnetic resonance spectroscopy support the presence of transient radical species in FtmOx1 catalysis. Our results help to unravel the novel mechanism for this endoperoxide formation reaction.

Synthesis of Sterically Hindered α-Hydroxycarbonyls through Radical-Radical Coupling.

We describe a synthetic approach to sterically hindered α-hydroxy carbonyl compounds through radical-radical coupling. An organic photoredox catalysis reaction converts an aliphatic carboxylic acid and α-ketocarbonyl to a transient alkyl radical and a persistent ketyl radical, respectively, which couple selectively based on the persistent radical effect. This protocol allows the use of primary, secondary, and tertiary aliphatic carboxylic acids to introduce various alkyl substituents onto ketone moieties of α-ketocarbonyls under mild reaction conditions.

Revisiting magnetic field effects in homogeneous medium and bio-mimicking environments with emphasis on acridine derivatives

A weak external magnetic field, very close to the hyperfine interactions of the system, can acts as a tool to monitor spin dynamics and assess distance between the components of the spin-correlated transient radical pair or radical ion pair (RIP). The present review focuses on the magnetic field effect (MFE) on the photo-induced electron-transfer (PET) reactions among acridine derivatives and classical as well as biological electron acceptor or donor moieties, which produce spin-correlated RIPs, in homogeneous solvents, heterogeneous micellar media and in biological nanocavities of proteins. Although a confined medium is preferred to observe prominent MFE, yet unanticipated MFE on PET between acridine derivatives [Acridone (AD) and Acridine Yellow (AY)] and classical electron donors is obtained even in homogeneous medium when it consists of impurities like water molecules. In a comparative study of interaction of another acridine derivative, Proflavin (PF+) with two electron donors which are amines of aromatic nature, MFE on PET reveal that the bulk and the structure of the electron donor govern the mechanism as well as the spin dynamics of PET. While studying interaction of PF+ with a different amine which is aliphatic in nature, MFE on PET implies that it is the nature of the solvent matrix which determines the spin dynamics of PET. The cause of discrepancy in the experimental and calculated values of B1/2 for 9-amino acridine – methyl viologen system has been delineated. Apart from micellar medium, prominent MFE on PET is also observed while studying the interaction of PF+, AY and AD with tryptophan residues present in the nanocavities of serum albumins since the inter-radical distance within primary geminate RIP is enough to make exchange interaction negligible.

Photoinduced emissive naphthalenediimide radical anion in the confinement of cucurbituril nanocavity; in situ generation of gold nanoparticles

Supramolecularly assembled building blocks, especially those based on π stacked organic or inorganic redox active materials have found encouraging applications in recent years due to their electron-accepting nature and easy structural manipulations. In this regard, by employing various spectroscopic, thermodynamic and imaging measurements we establish the generation, stabilization and in situ reaction of a novel supramolecularly supported emissive radical anions through host–guest interaction of N, Ń-bis[2-(2-aminoethyl)benzimidazolyl] naphthalene diimide (BzNDI) with Cucubit[n]uril (CB7 and CB8) macrocycles in aqueous medium. While the CB7 and CB8 hosts revealed distinct interactions with the BzNDI, the CB8 complexation displayed a novel excimer emission band in the 523 nm region, which originated from dimeric inclusion of BzNDI dyes in to the larger CB8 cavity. These CB7/CB8 stabilized BzNDI complexes undergo photoinduced electron transfer process to generate respective radical anions. These transient radical anions held in the cucurbituril nanocavities displayed characteristic emission spectra in the visible region and longer lived (τav ~ 6.5 ns) radical excited states and the radical anions are found to be reversible to their parent complex under ambient condition in ~1–2 h. This dynamic stability window of the radical anions has been used for the in situ reduction of Au3+ to generate stable AuNPs. It is noteworthy that this chemistry was not observed with BzNDI in the absence of CB7/CB8 host interaction. We foresee that the demonstrated stimuli responsive supramolecular approach has the potential for the controlled assembly of smart materials, radical polymerization, molecular electronics and other gated radical induced reactions.

Selective Oxidation of Transient Organic Radicals in the Presence of Gold Nanoparticles.

The ability of gold nanoparticles (AuNPs) to catalyze reactions involving radicals is poorly studied. However, AuNPs are used in applications where chemical reactions involving transient radicals occur. Herein, we investigate AuNPs’ catalytic effect on 2-propanol oxidation and acetanilide hydroxylation in aqueous solutions under ionizing radiation at room temperature. In both cases, the presence of AuNPs led to selective oxidation of organic radicals, significantly changing the products’ composition and ratio. Based on these observations, we stress how AuNPs’ catalytic activity can affect the correctness of reactive oxygen species concentration determination utilizing organic dyes. We also provide a discussion on the role of AuNPs’ catalytic activity in the radiosensitization effect actively studied for radiotherapy.

STARGATE: A new instrument for high-resolution photodissociation spectroscopy of cold ionic species

Spectroscopy of transient anions and radicals by gated and accelerated time-of-flight experiment is a new spectrometer developed in UCLouvain. This instrument measures high-resolution photodissociation spectra of mass-selected ions by the combination of a time-of-flight spectrometer including a specific gating, bunching, and re-referencing unit with a nanosecond pulsed dye laser, a pulsed deflection, and an energy selector. The ionic species are generated in a supersonic jet expansion by means of an electric discharge or by the impact of electrons coming from an electron gun. The versatility of the molecular systems that can be addressed by this instrument is illustrated by the presentation of mass spectra of cations, anions, and ionic clusters formed from different gas mixtures and backing pressures. The high-resolution spectrum of the A~2Σ+(002)←X~2Π3/2(000) and A~2Σ+(002)←X~2Π1/2(000) rovibronic bands of N2O+ has been measured and analyzed to provide refined molecular parameters in the A~2Σ+(002) upper state. The A~2Σ+(002)←X~2Π3/2(000) band has been used to evaluate the quality of the experimental setup in terms of rotational temperature, time of measurement for certain signal to noise ratio, and the accuracy of the determination of the wavenumber scale.

Synthesis of Acridinium Photocatalysts via Site-Selective C–H Alkylation

Acridinium dyes have been broadly used as photocatalysts, but it remains synthetically challenging to fine-tune their catalytic performance by functionalization of their structural cores. Acridiniu...

Controlling Radical Relay Processes with Visible Light

Harnessing free radical intermediates for selective functionalization of organic compounds has been widely demonstrated under photocatalytic conditions requiring a distinct photocatalyst. In this issue of Chem, Seo, Chang, and co-workers demonstrate an alternative photocatalyst-free light-mediated approach that allows efficient amidation of aldehydes via N-centered radical intermediate.

Regulation of biochar mediated catalytic degradation of quinolone antibiotics: Important role of environmentally persistent free radicals

Antibiotic pollution threatens aquatic ecosystems and water supplies, so analysis of ecofriendly remediation approaches like biochars with catalytic degradation abilities is a top priority. In this work, quinolone antibiotics were degraded by activating oxidants to generate transient radicals using the environmentally persistent free radicals (EPFRs) carried by biochar. The physical and chemical characterization confirmed that biochar is suitable for the removal of organic pollutants. By regulating biochar preparation parameters, it was found that EPFR generation peaked at 500 °C. As the temperature increased from 300 °C to 500 °C, the EPFRs changed from oxygen-centered radicals (g > 2.0040) to carbon-centered radicals (g < 2.0030). The catalytic degradation efficiencies of the EPFR activated oxidants from large to small were: peroxydisulfate (PDS), peroxymonosulfate (PMS), H2O2 and flowing O2. The combined actions of SO4•− and •OH effectively degraded antibiotics. The results showed that biochar activating persulfate is a promising technique for the degradation of antibiotics.

The Effect of Viscosity on the Coupling and Hydrogen-Abstraction Reaction between Transient and Persistent Radicals?

Abstract The effect of viscosity on the radical termination reaction between a transient radical and a persistent radical undergoing a coupling reaction (Coup) or hydrogen abstraction (Abst) was examined. In a non-viscous solvent, such as benzene (bulk viscosity ηbulk &amp;lt; 1 mPa s), all the transient radicals studied exclusively coupled with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) with &amp;gt;99% Coup/Abst selectivity, but Coup/Abst decreased as the viscosity increased (89/11 in PEG400 at 25 °C [ηbulk = 84 mPa s]). While bulk viscosity is a good parameter to predict the Coup/Abst selectivity in each solvent, microviscosity is the more general parameter. Poly(methyl methacrylate) (PMMA)-end radicals had a more significant viscosity effect than polystyrene (PSt)-end radicals, and the Coup/Abst ratio of the former dropped to 50/50 in highly viscous media (ηbulk = 3980 mPa s), while the latter maintained high Coup/Abst selectivity (84/16). These results, together with the low thermal stability of dormant PMMA-TEMPO species compared with that of PSt-TEMPO species, are attributed to the limitation of the nitroxide-mediated radical polymerization of MMA. While both organotellurium and bromine compounds were used as precursors of radicals, the former was superior to the latter for the clean generation of radical species.