Persistent Radicals Research Articles

Tuneable Redox Chemistry and Electrochromism of Persistent Symmetric and Asymmetric Azine Radical Cations.

Molecular organic radicals have been intensively studied in the last decades, due to their interesting optical, magnetic and redox properties. Here we report the synthesis and characterisation of persistent organic radicals from one-electron oxidation of redox-active azines (RAAs), composed of two guanidinyl or related groups. By connecting two different groups together, asymmetric compounds result. In this way a series of compounds with varying redox potential is obtained that could be oxidised reversibly to the mono- and the dicationic charge states. The accessible redox states were fully determined by chemical redox reactions. The standard Gibbs free energy change for disproportionation of the radical monocation into the dication and the neutral molecule in solution, estimated from cyclovoltammetric measurements, varies between 43 and 71 kJ mol-1 . While the neutral RAAs absorb predominately UV light, the radical monocations display strong absorptions covering almost the entire visible region and extending for some compounds into the NIR region. A detailed analysis of this highly reversible electrochromism is presented, and the fast switching characteristics are demonstrated in an electrochromic test device.

Cover Feature: Alkali‐Metal Aminotroponiminates: Selectivities and Equilibria in Reversible Radical Coupling of Delocalized π‐Electron Systems (Chem. Eur. J. 51/2019)

Persistent radicals play an increasingly important role in synthesis and catalysis. Stabilization of radicals may be achieved by incorporation into a delocalized π-electron system, generating multiple potentially reactive sites. Using aminotroponiminates (ATIs) as a model system, this work addresses chemo-, regio-, and diastereoselectivities as well as equilibria in reactions of persistent radicals. Unexpectedly, dramatic differences in the reactivity of Li, Na, and K-ATIs were observed. More information can be found in the Full Paper by C. Lichtenberg et al. on page 11891.

Cross‐Coupling Reaction of Dimer‐Derived Persistent Tertiary‐Carbon‐Centered Radicals with Azo Compounds

AbstractCross‐coupling reactions using tertiary carbon‐centered radicals are an important class of transformations for constructing C(sp3)−C(sp3) bonds, but the use of dimers as precursors of the persistent radicals is quite rare. Herein, we describe a radical‐based cross‐coupling reaction between dimers (prepared from 2‐oxindoles and benzofuranones) and azo compounds that proceeds simply upon heating the reaction mixture. We present a conformational analysis of the dimers and we characterize the generation of a persistent radical via cleavage of the elongated C(3)−C(3’) σ‐bond. The behavior of the dimers in solution was characterized by spectroscopic analysis, helping to provide a basis for expanding the substrate scope of the cross‐coupling reaction.

Silk-Like Protein with Persistent Radicals Identified in Oyster Adhesive by Solid-State NMR.

The cement produced by the Eastern oyster, Crassostrea virginica, may provide blueprints for waterproof biocompatible adhesives synthesized under benign conditions. The composition of this organic-inorganic composite, and of an organic extract, was characterized by 13C and 1H solid-state NMR and also compared withC. virginica shell and its organic extract. Quantification of the organic fraction by 13C and 1H NMR spectroscopy consistently showed 3 wt % organics in cement, which was higher than the 1.2 wt % in the shell. According to 13C NMR with spectral editing, the organic fraction of cement consisted of 73% protein, 25% polysaccharide, and 2% lipid. The organic acid-insoluble extract from the cement was mostly made up of protein remarkably rich in alanine and glycine. The unusual amino acid content matched the composition of silk-like proteins in the C. virginica or C. gigas genomes, including spidron-1-like and shelk2 previously found to be upregulated at the mantle edge. The corresponding extract from the shell contained 32% glycine and was also enriched in serine but not alanine, which was consistent with a previous wet-chemistry study. The 13C and 1H NMR spin-lattice relaxation in the organic component of cement and the acid-insoluble extract was 4-40 times faster than in the shell and showedpronounced nonexponentiality, indicating a high concentration of persistent radicals in the organic components of cement, in agreement with a prior EPR study. The presence of radicals in the acid-insoluble cement fraction was confirmed by observation of a paramagnetic shift anisotropy. 13C NMR corroborated prior observations that the calcium carbonate in the shell and pseudonacre was mostly calcite, whereas cement had an enhanced aragonite fraction. Surprisingly, 1H-13C NMR indicated that aragonite in cement was more distant from the organic fraction than wascalcite. These results help advance our understanding of how oysters achieve adhesion within their wet environment.

Synthesis, Physical Properties, and Reactivity of Persistent π-Conjugated Carbon-Centered Radicals

Synthesis, Physical Properties, and Reactivity of Persistent π-Conjugated Carbon-Centered Radicals

Generation and EPR Spectroscopy of the First Silenyl Radicals, R2C=Si.−R: Experiment and Theory

AbstractThe first two persistent silenyl radicals (R2C=Si.−R), with a half‐life (t1/2) of about 30 min, were generated and characterized by electron paramagnetic resonance (EPR) spectroscopy. The large hyperfine coupling constants (hfccs) (a(29Siα)=137.5–148.0 G) indicate that the unpaired electron has substantial s character. DFT calculations, which are in good agreement with the experimentally observed hfccs, predict a strongly bent structure (∡C=Si−R=134.7–140.7°). In contrast, the analogous vinyl radical, R2C=C.−R (t1/2≈3 h), exhibits a small hfcc (a(13Cα)=26.6 G) and has a nearly linear geometry (∡C=C−R=168.7°).

Role of radicals in carbon clustering and soot inception: A combined EPR and Raman spectroscopic study

Some aspects of soot formation from gas phase molecules at high temperatures are still unclear. Aromatic π-radicals may be key elements for a change in the model of carbon clustering and particle formation. However, experimental investigations are still needed on the radical nature of molecules and particles in flames and on their roles in the transition from molecules to incipient molecular clusters and their further evolution to mature soot.In this paper, we present electron paramagnetic resonance (EPR) and Raman spectroscopy measurements of particles collected in an ethylene-rich premixed flame at various residence times during nucleation. The experimental results, combined with measurement of the particle size distribution by a differential mobility analyzer, are used to investigate the role of radicals in particle nucleation and rearrangement of aromatic molecules in just-nucleated particles. For all the sampled particles, an EPR signal typical of persistent carbon-centered aromatic radicals is measured. An abrupt change in the EPR signal intensity, which is characteristic of stronger supramolecular interactions, is observed when the size distribution changes from monomodal to bimodal, as confirmed by Raman spectroscopy. Our experimental results indicate strong involvement of π-radicals during particle nucleation and growth. The paramagnetic/radical nature of the sampled particles is discussed on the basis of recent studies on the role of resonantly stabilized radicals in soot nucleation. The presence of localized π-electrons on the edge of aromatic soot constituents and their role in carbon clustering are also discussed.

Generation and EPR Spectroscopy of the First Silenyl Radicals, R2 C=Si. -R: Experiment and Theory.

The first two persistent silenyl radicals (R2 C=Si. -R), with a half-life (t1/2 ) of about 30 min, were generated and characterized by electron paramagnetic resonance (EPR) spectroscopy. The large hyperfine coupling constants (hfccs) (a(29 Siα )=137.5-148.0 G) indicate that the unpaired electron has substantial s character. DFT calculations, which are in good agreement with the experimentally observed hfccs, predict a strongly bent structure (∡C=Si-R=134.7-140.7°). In contrast, the analogous vinyl radical, R2 C=C. -R (t1/2 ≈3 h), exhibits a small hfcc (a(13 Cα )=26.6 G) and has a nearly linear geometry (∡C=C-R=168.7°).

Conducting carbon films with covalent binding sites for biomolecule attachment

We report an electrically conductive carbon film with controllable hydrophilic properties that offers a covalent binding surface containing radicals for biomolecule attachment without using chemical linkers. Films were deposited from an acetylene-containing plasma using plasma immersion ion implantation during growth and subsequently annealed under vacuum. Electrical conductivity, spin density, contact angle, surface energy, surface composition, and covalent binding capability were studied as a function of annealing temperature, revealing three distinct regions. In the first region, surface energy is dominated by polar groups. In the second region, the polar groups are expelled, creating unpaired electrons that dominate the polar component of the surface energy. In the third region, the electrical conductivity rises and the polar component of surface energy falls as the unpaired electrons recombine, leading to an optimum combination of surface energy, spin density, and electrical conductivity for biological applications. It is proposed that persistent radicals are responsible for both high wettability and covalent binding properties. Covalently attached enzyme molecules on the C film can resist stringent washing with detergents. The C films offer the functions of conducting polymers, but with the added features of controllable wettability and a covalent binding capability.

Synthesis, Physical Properties, and Reactivity of Stable, π-Conjugated, Carbon-Centered Radicals.

Recently, long-lived, organic radical species have attracted much attention from chemists and material scientists because of their unique electronic properties derived from their magnetic spin and singly occupied molecular orbitals. Most stable and persistent organic radicals are heteroatom-centered radicals, whereas carbon-centered radicals are generally very reactive and therefore have had limited applications. Because the physical properties of carbon-centered radicals depend predominantly on the topology of the π-electron array, the development of new carbon-centered radicals is key to new basic molecular skeletons that promise novel and diverse applications of spin materials. This account summarizes our recent studies on the development of novel carbon-centered radicals, including phenalenyl, fluorenyl, and triarylmethyl radicals.

Visible-light-responsive surface-modified TiO2 powder with 4-chlorophenol: A combined experimental and DFT study

The visible-light-responsive inorganic-organic hybrid was prepared by surface modification of commercial TiO2 powder (Degussa P25) with 4-chlorophenol (4-CP). The optical absorption of the hybrid material is red-shifted compared to unmodified TiO2 powder due to the surface charge transfer complex (CTC) formation. The experimental results are supported by the density functional theory (DFT) calculations of the corresponding model cluster. The calculated electronic excitation spectrum is in agreement with the measured reflection spectrum of surface-modified TiO2 powder with 4-CP. The paramagnetic species, generated in the unmodified and surface-modified TiO2 powders upon excitation with ultraviolet and visible light, were identified using low-temperature electron paramagnetic resonance (EPR) spectroscopy. The formation of trapped electrons (Ti(III) centers) and the persistent oxygen-centered organic radicals indicated the photoinduced electron transfer from the chemisorbed 4-chlorophenol to the conduction band of TiO2.

Anthracene-Attached Persistent Tricyclic Aromatic Hydrocarbon Radicals.

Anthracene-attached tricyclic aromatic hydrocarbon radicals having different central polygons, Ant-5, Ant-6, and Ant-7, were synthesized to evaluate the role of an anthracene substituent group in the stability and reactivity of tricyclic aromatic hydrocarbon radicals. The bulky anthryl group effectively protects a carbon atom with high spin density, resulting in high persistence of the radicals. On the other hand, the combination of the anthryl group and the tricyclic aromatic scaffold makes the molecular structure drastically change from a twisted form to a folded form and an unpaired electron moves into the anthryl moiety, eventually affording a tail-to-tail σ-dimer.

UV-irradiation of self-assembled triphenylamines affords persistent and regenerable radicals.

UV-irradiation of assembled urea-tethered triphenylamine dimers results in the formation of persistent radicals, whereas radicals generated in solution are reactive and quickly degrade. In the solid-state, high quantities of radicals (approximately 1 in 150 molecules) are formed with a half-life of one week with no significant change in the single crystal X-ray diffraction. Remarkably, after decay, re-irradiation of the solid sample regenerates the radicals to their original concentration. The photophysics upon radical generation are also altered. Both the absorption and emission are significantly quenched without external oxidation likely due to the delocalization of the radicals within the crystals. The factors that influence radical stability and generation are correlated to the rigid supramolecular framework formed by the urea tether of the triphenylamine dimer. Electrochemical evidence demonstrates that these compounds can be oxidized in solution at 1.0 V vs. SCE to generate radical cations, whose EPR spectra were compared with spectra of the solid-state photogenerated radicals. Additionally, these compounds display changes in emission due to solvent effects from fluorescence to phosphorescence. Understanding how solid-state assembly alters the photophysical properties of triphenylamines could lead to further applications of these compounds for magnetic and conductive materials.

UV cell stress induces oxidative cyclization of a protective reagent for DNA damage reduction in skin explants

UV irradiation is a major driver of DNA damage and ultimately skin cancer. UV exposure leads to persistent radicals that generate ROS over prolonged periods of time. Toward the goal of developing long-lasting antioxidants that can penetrate skin, we have designed a ROS-initiated protective (RIP) reagent that, upon reaction with ROS (antioxidant activity), self-cyclizes and then releases the natural product apocynin. Apocynin is a known antioxidant and inhibitor of NOX oxidase enzymes. A key phenol on the compound 1 controls ROS-initiated cyclization and makes 1 responsive to ROS with a EC50 comparable to common antioxidants in an ABTS assay. In an in vitro DNA nicking assay, the RIP reagent prevented DNA strand breaks. In cell-based assays, the reagent was not cytotoxic, apocynin was released only in cells treated with UVR, reduced UVR-induced cell death, and lowered DNA lesion formation. Finally, topical treatment of human skin explants with the RIP reagent reduced UV-induced DNA damage as monitored by quantification of cyclobutane dimer formation and DNA repair signaling via TP53. The reagent was more effective than administration of a catalase antioxidant on skin explants. This chemistry platform will expand the types of ROS-activated motifs and enable inhibitor release for potential use as a long-acting sunscreen.

Formation of persistent organic diradicals from N,N\u2032-diphenyl-3,7-diazacyclooctanes

N,N′-Diphenyl-3,7-diazacyclooctane and structurally related N,N′-diphenylbispidine derivatives react with silver(I) ions in a high-yielding C–C coupling reaction to produce dication–diradical species, with the silver ions serving a double function both as template and as an oxidant. The resulting bis(benzidino)phane derivatives are persistent organic radicals, stable for several months in solution as well as in the solid state, at room temperature and above, as well as being exposed to the atmosphere. The molecular structure features a double-decker cyclophane motif, stabilized by intramolecular π-dimerization of two delocalized benzidinium radical segments. Intermolecular π-dimers are formed in the solid state.Graphical abstract

Enhancing the Stability of Photogenerated Benzophenone Triplet Radical Pairs through Supramolecular Assembly.

Supramolecular assembly of urea-tethered benzophenone molecules results in the formation of remarkably persistent triplet radical pairs upon UV irradiation at room temperature, whereas no radicals were observed in solution. The factors that lead to emergent organic radicals are correlated with the microenvironment around the benzophenone carbonyl, types of proximal hydrogens, and the rigid supramolecular network. The absorption spectra of the linear analogues were rationalized using time-dependent density functional theory calculations on the crystal structure and in dimethyl sulfoxide, employing an implicit solvation model to describe structural and electronic solvent effects. Inspection of the natural transition orbitals for the more important excitation bands of the absorption spectra indicates that crystallization of the benzophenone-containing molecules should present a stark contrast in photophysical properties versus that in solution, which was indeed reflected by their quantum efficiencies upon solid-state assembly. Persistent organic radicals have prospective applications ranging from organic light-emitting diode technology to NMR polarizing agents.

A Series of Two-Coordinate Group-15 Element (P, As, Sb, Bi) Centered Radicals Having Bulky Alkyl Groups

Abstract Two-coordinate group-15 element centered radicals that bear a lone pair and an unpaired electron on the same group-15 atoms have received much attention in group-15 element chemistry. We previously synthesized an isolable dialkylphosphinyl radical, 2,2,5,5-tetrakis(trimethylsilyl)-1-phosphacyclopentane-1-yl (1P) and its antimony and bismuth analogues (stibinyl radical 1Sb and bismuthinyl radical 1Bi) as persistent radicals. We report herein (1) synthesis of an isolable cyclic dialkylarsinyl radical 1As that exists in the radical form both in solution and in the solid state and (2) comprehensive study of a series of neutral two-coordinate pnictogen-centered radicals (1P, 1As, 1Sb, 1Bi) including UV-vis spectra, redox properties, and reactions.

Persistent P-Stabilized Boryl Radicals with Bulky Substituents at Boron

Two new P-stabilized boryl radicals [Ph2P(naph)BAr] (Ar = Tip and Ter) have been prepared and characterized by electron paramagnetic resonance spectroscopy. These radicals are persistent for several days in solution at room temperature. The high steric congestion at boron does not prevent radical reactivity. Two different types of dimerization equilibrium have been observed. The structures of the dimers have been unambiguously established by X-ray diffraction crystallography.

Probing cardiac metabolism by hyperpolarized 13C MR using an exclusively endogenous substrate mixture and photo-induced nonpersistent radicals.

To probe the cardiac metabolism of carbohydrates and short chain fatty acids simultaneously in vivo following the injection of a hyperpolarized 13 C-labeled substrate mixture prepared using photo-induced nonpersistent radicals. Droplets of mixed [1-13 C]pyruvic and [1-13 C]butyric acids were frozen into glassy beads in liquid nitrogen. Ethanol addition was investigated as a means to increase the polarization level. The beads were irradiated with ultraviolet light and the radical concentration was measured by ESR spectroscopy. Following dynamic nuclear polarization in a 7T polarizer, the beads were dissolved, and the radical-free hyperpolarized solution was rapidly transferred into an injection pump located inside a 9.4T scanner. The hyperpolarized solution was injected in healthy rats to measure cardiac metabolism in vivo. Ultraviolet irradiation created nonpersistent radicals in a mixture containing 13 C-labeled pyruvic and butyric acids, and enabled the hyperpolarization of both substrates by dynamic nuclear polarization. Ethanol addition increased the radical concentration from 16 to 26 mM. Liquid-state 13 C polarization was 3% inside the pump at the time of injection, and increased to 5% by addition of ethanol to the substrate mixture prior to ultraviolet irradiation. In the rat heart, the in vivo 13 C signals from lactate, alanine, bicarbonate, and acetylcarnitine were detected following the metabolism of the injected substrate mixture. Copolarization of two different 13 C-labeled substrates and the detection of their myocardial metabolism in vivo was achieved without using persistent radicals. The absence of radicals in the solution containing the hyperpolarized 13 C-substrates may simplify the translation to clinical use, as no radical filtration is required prior to injection.

Radicals in natural product synthesis.

Free radical intermediates have intrigued chemists since their discovery, and an ever-increasing appreciation for their unique reactivity has resulted in the widespread utilization of these species throughout the field of chemical synthesis. This is most evident from the recent surge in the application of intermolecular radical reactions that feature in complex molecule syntheses. This tutorial review will discuss the diverse methods utilized for radical generation and reactivity to form critical bonds in natural product total synthesis. In particular, stabilized (e.g. benzyl) and persistent (e.g. TEMPO) radicals will be the primary focus.