Radical Pair Research Articles

Frustrated Radical Pairs: From Fleeting Intermediates to Isolable Species.

We present the design and comprehensive investigation of stable para-substituted triarylamine-2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) radical ion pairs (RIPs) generated via single-electron transfer (SET). We quantified the degree of SET in both solution and solid phases, utilising a suite of spectroscopic techniques including IR, EPR, NMR, and single-crystal X-ray diffraction (SC-XRD). Our findings reveal that the extent of SET is significantly influenced by the nature of the substituents (MeO > tBu > Br) and the polarity of the solvent (MeCN > DCM > toluene). The radical ion pair [(pMeOPh)3N]•+[DDQ]•- was unambiguously identified using EPR and UV-vis spectroscopy, and its structure was confirmed by SC-XRD. Detailed analysis indicates an open-shell singlet ground state with a thermally accessible triplet state, as corroborated by EPR, magnetic susceptibility measurements, and DFT calculations. This study offers crucial insights into the mechanistic pathways of RIP formation and tuning both in solution and solid states, laying the groundwork for future exploration of their reactivity and potential applications.

Numerical and analytical inspection of magnetic field effects in the radical pair mechanism by a simplified rate equation model.

The radical pair mechanism is by now the most prominent candidate for a biologically relevant quantum effect of magnetic fields. Recently, N. Ikeya and J. R. Woodward demonstrated a magnetic field effect for sub-extremely low frequency (ELF) fields in the mT range by investigating the autofluorescence spectrum of flavin adenine dinucleotide in living HeLa cells. We apply a simple rate equation model to show numerically and analytically that magnetic field effects can be expected to exist in the whole ELF range.

Cryptochrome magnetoreception: time course of photoactivation from non-equilibrium coarse-grained molecular dynamics

Magnetoreception, the ability to sense magnetic fields, is widespread in animals but remains poorly understood. The leading model links this ability in migratory birds to the photo-activation of the protein cryptochrome. Magnetic information is thought to induce structural changes in cryptochrome via a transient radical pair intermediate. This signal transduction pathway has been the subject of previous all-atom molecular dynamics (MD) simulations, but insights were limited to short timescales and equilibrium structures. To address this, we developed a non-equilibrium coarse-grained MD simulation approach, exploring cryptochrome’s photo-reduction over 20 replicates of 20 µs each. Our results revealed significant structural changes across the protein, with an overall time constant of 3 µs. The C-terminal (CT) region responded on a timescale of 4.7 µs, followed by the EEE-motif, while the phosphate binding loop (PBL) showed slower dynamics (9 µs). Network analysis highlighted direct pathways connecting the tryptophan tetrad to the CT, and distant pathways involving the EEE and PBL regions. The CT-dynamics are significantly impacted by a rearrangement of tryptophan residues in the central electron transfer chain. Our findings underscore the importance of considering longer timescales when studying cryptochrome magnetoreception and highlight the potential of non-equilibrium coarse-grained MD simulations as a powerful tool to unravel protein photoactivation reactions.

Quantum phenomena in biological systems

Quantum biology is a modern field of research that aims to understand how quantum effects can affect the chemistry underlying various biological processes. This paper reviews several examples of biological processes where quantum effects might play a notable role. Initially, the photon capture mechanism present in vision is discussed, where the energy of the photon is used to cause conformational changes to chromophoric proteins. The second example elaborates the highly efficient energy transfer process present in photosynthesis and discusses, in particular, how the random quantum walk process may enhance the performance drastically. Subsequently, the vertebrate magnetoreception, and the possible associated role of the radical pair mechanism in the process is considered. The review concludes with the discussion of some speculative ideas of putative quantum effects arising in neural processes.

RadicalPy: A Tool for Spin Dynamics Simulations.

Radical pairs (electron-hole pairs, polaron pairs) are transient reaction intermediates that are found and exploited in all areas of science, from the hard realm of physics in the form of organic semiconductors, spintronics, quantum computing, and solar cells to the soft domain of chemistry and biology under the guise of chemical reactions in solution, biomimetic systems, and quantum biology. Quantitative analysis of radical pair phenomena has historically been successful by a few select groups. With this in mind, we present an intuitive open-source framework in the Python programming language that provides classical, semiclassical, and quantum simulation methodologies. A radical pair kinetic rate equation solver, Monte Carlo-based spin dephasing rate estimations, and molecule database functionalities are implemented. We introduce the kine-quantum method, a new approach that amalgamates classical rate equations, semiclassical, and quantum techniques. This method resolves the prohibitively large memory requirement issues of quantum approaches while achieving higher accuracy, and it also offers wavelength-resolved simulations, producing time- and wavelength-resolved magnetic field effect simulations. Model examples illustrate the versatility and ease of use of the software, including the new approach applied to the magnetosensitive absorption and fluorescence of flavin adenine dinucleotide photochemistry, spin-spin interaction estimation from molecular dynamics simulations on radical pairs inside reverse micelles, radical pair anisotropy inside proteins, and triplet exciton pairs in anthracene crystals. The intuitive interface also allows this software to be used as a teaching or learning aid for those interested in the field of spin chemistry. Furthermore, the software aims to be modular and extensible, with the aim to standardize how spin dynamics simulations are performed.

Enhancing Photogenerated Radical Pair Properties in Donor-Chromophore-Acceptor Systems for Quantum Information Applications.

We report on new donor-chromophore-acceptor triads BDX-ANI-NDI and BDX-ANI-xy-NDI where the BDX donor is 2,2,6,6-tetramethylbenzo[1,2-d;4,5-d]bis[1,3]dioxole, the ANI chromophore is 4-(N-piperidinyl)naphthalene-1,8-dicarboximide, the NDI acceptor is naphthalene-1,8:4,5-bis(dicarboximide), and xy is a 2,5-xylyl spacer. The results on these compounds are compared to the analogous derivatives having a p-methoxyaniline (MeOAn) as the donor. BDX•+ has no nitrogen atoms and only a single hydrogen atom coupled to its unpaired electron spin, and therefore has significantly decreased hyperfine interactions compared to MeOAn•+. We use femtosecond transient absorption (fsTA) and nanosecond TA (nsTA) spectroscopies, the latter with an applied static magnetic field, to study the charge transfer dynamics and determine the spin-spin exchange interaction (J) for BDX•+-ANI-NDI•- and BDX•+-ANI-xy-NDI•- at both ambient and cryogenic temperatures. Time-resolved electron paramagnetic resonance (EPR) and pulse-EPR measurements on these spin-correlated radical pairs (SCRPs) were used to probe their spin dynamics. We demonstrate that BDX•+-ANI-xy-NDI•- has an unusually long lifetime of ∼550 μs in glassy butyronitrile (PrCN) at 85 K, which makes it useful for pulse-EPR studies that target quantum information science (QIS) applications. We also show that rotation of the BDX group about the single bond linking it to the neighboring phenyl group has a significant impact on the spin dynamics, and in particular the magnitude of J. By comparing the results on these compounds to the analogous MeOAn series, insights into design principles for creating improved spin-correlated radical pair systems for QIS studies are obtained.

Frequency-Dependent Antioxidant Responses in HT-1080 Human Fibrosarcoma Cells Exposed to Weak Radio Frequency Fields.

This study explores the complex relationship between radio frequency (RF) exposure and cancer cells, focusing on the HT-1080 human fibrosarcoma cell line. We investigated the modulation of reactive oxygen species (ROS) and key antioxidant enzymes, including superoxide dismutase (SOD), peroxidase, and glutathione (GSH), as well as mitochondrial superoxide levels and cell viability. Exposure to RF fields in the 2-5 MHz range at very weak intensities (20 nT) over 4 days resulted in distinct, frequency-specific cellular effects. Significant increases in SOD and GSH levels were observed at 4 and 4.5 MHz, accompanied by reduced mitochondrial superoxide levels and enhanced cell viability, suggesting improved mitochondrial function. In contrast, lower frequencies like 2.5 MHz induced oxidative stress, evidenced by GSH depletion and increased mitochondrial superoxide levels. The findings demonstrate that cancer cells exhibit frequency-specific sensitivity to RF fields even at intensities significantly below current safety standards, highlighting the need to reassess exposure limits. Additionally, our analysis of the radical pair mechanism (RPM) offers deeper insight into RF-induced cellular responses. The modulation of ROS and antioxidant enzyme activities is significant for cancer treatment and has broader implications for age-related diseases, where oxidative stress is a central factor in cellular degeneration. The findings propose that RF fields may serve as a therapeutic tool to selectively modulate oxidative stress and mitochondrial function in cancer cells, with antioxidants playing a key role in mitigating potential adverse effects.

Nuclear hyperpolarization in electron-transfer proteins: Revealing unexpected light-induced 15N signals with field-cycling magic-angle spinning NMR

The solid-state photo-CIDNP (photo-chemically induced dynamic nuclear polarization) effect allows for nuclear hyperpolarization, i.e., non-Boltzmann nuclear spin population. The effect relies on the light-induced formation of a spin-correlated radical pair (SCRP) and has been observed in various photosynthetic reaction center (RC) proteins and flavin-containing light, oxygen, voltage (LOV) proteins. Both systems exhibit strongly enhanced NMR signals originating from the electron transfer partners. Here, we present experimental data on the magnetic field dependence of the 15N solid-state photo-CIDNP effect in both phototropin LOV1 C57S from Chlamydomonas reinhardtii and the bacterial photosynthetic RC from Rhodobacter sphaeroides. Using a pneumatic field-cycling system, samples containing a frozen solution of the proteins are explored between 0.25 T and 9.4 T. Both systems yield hyperpolarized 15N NMR signals across the entire magnetic field range originating from the electron transfer moieties. Also, in both systems, hyperpolarized signals from unexpected positions are detected between 1.0 T and 2.0 T: position N-1 of the flavin in the LOV1 protein and the τ-N of the axial magnesium-coordinating histidine of the donor. A first attempt to explain the occurrence of these unexpected signals based on quantum chemical calculations is presented.

Kinetics of Electron Transfer between Redox Cofactors in PhotosystemI Measured by High-Frequency EPR Spectroscopy.

The kinetics of the primary electron donor P700+ and the quinone acceptor A1- redox transitions were simultaneously studied for the first time in the time range of 200μs-10ms using high-frequency pulse Q-band EPR spectroscopy at cryogenic temperatures in various complexes of photosystemI(PSI) from the cyanobacterium Synechocystissp. PCC 6803. In the A1-core PSI complexes that lack 4Fe4S clusters, the kinetics of the A1- andP700+ signals disappearance at 100K were similar and had a characteristic time of τ≈500μs, caused by charge recombination in the P700+A1A- ion-radical pair in the A branch of redox cofactors. The kinetics of the backward electron transfer from A1B- to P700+ in the B branch of redox cofactors with τ<100μs could not be resolved due to time limitations of the method. In the native PSI complexes with a full set of redox cofactors and in the FX-core complexes, containing the 4Fe4S cluster FX, the kinetics of the A1- signal was significantly faster than that of the P700+ signal. The disappearance of the A1- signal had a characteristic time of 280-350μs; it was suggested that, in addition to the backward electron transfer from A1A- to P700+ with τ≈500μs, its kinetics also includes the forward electron transfer from A1A- to the 4Fe4S cluster FX, which had slowed down to 150-200μs. In the kinetics of P700+ reduction, it was possible to distinguish components caused by the backward electron transfer from A1-(τ≈500μs) and from 4Fe4S clusters (τ=1ms for the FX-core and τ>5ms for native complexes). These results are in qualitative agreement with the data on the kinetics of P700+ reduction obtained previously using pulse absorption spectrometry at cryogenic temperatures.

An unusual triplet population pathway in the Reaction Centre of the Chlorophyll-d binding Photosystem I of A. marina, as revealed by a combination of TR-EPR and ODMR spectroscopies

Photo-induced Chlorophyll (Chl) triplet states in the isolated Photosystem I (PSI) of Acaryochloris marina, that harbours Chl d as its main pigment, were investigated by Optically Detected Magnetic Resonance (ODMR) and Time-Resolved Electron Paramagnetic Resonance (TR-EPR), and as a function of pre-illumination of the sample under reducing redox poising. Fluorescence Detected Magnetic Resonance (FDMR) allowed resolving four Chl d triplet (3Chl d) populations (T1-T4) both in untreated and illuminated samples in the presence of ascorbate and N,N,N′,N′-tetramethyl-p-phenylenediamine (TMPD). The FDMR signals increased following the pre-illumination treatment, particularly for the T3 and T4 populations, which are therefore sensitive to the redox state of PSI cofactors. Microwave-induced Triplet minus Singlet (TmS) spectra were detected in the |D|-|E| resonance window of the T3 and T4 triplets. These showed a broad singlet bleaching centred at 740 nm and also displayed complex spectral structure with several derivative-like features, indicating that both the T3 and T43Chl d populations are associated with the PSI reaction centre (RC) triplet, P3740. Parallel measurements by TR-EPR demonstrated that triplet signals observed under all conditions investigated are dominated by an electron spin polarisation (esp), which is typical of intersystem crossing, differently from what expected for recombination triplet states formed from a radical pair precursor. Moreover, stronger reductant conditions obtained by pre-illumination of the samples in the presence of dithionite and 5-methylphenazinium methyl sulfate (PMS) did not lead to a recombination triplet state esp, but rather to a decrease of the whole signal intensity. The energetics of A. marina PSI and the possible occurrence of distributions of cofactors redox properties are discussed in order to address the unexpected P3740 esp.

Frustrated Al/M Heterobimetallic Complexes (M = Cr, Mo, W) That Exhibit Both Lewis and Radical Pair Behavior.

Exploration of new heterobinuclear Al/M combinations is relevant to contemporary strategies for cooperative bond activation. Here, we report the synthesis and characterization of six new Al/M heterobimetallic complexes (M = Cr, Mo, W) that exhibit end-on "isocarbonyl"-type Al─O═C═M bridges with metalloketene character rather than featuring Al─M─C≡O motifs with metal-metal bonding. The new compounds were characterized experimentally by nuclear magnetic resonance and infrared spectroscopies and theoretically using density functional theory, natural bond orbital, and quantum theory of atoms in molecules calculations. Factors influencing Al─O═C═M vs Al─M─C≡O isomerism were probed both experimentally and computationally. Crossover experiments between different group VI Al/M derivatives and regioselective epoxide ring opening indicate that the Al/M complexes act as masked frustrated Lewis pairs in solution under certain conditions. However, crossover experiments between group VI Al/M complexes and a previously studied Al-Fe complex, as well as computational modeling, imply that the same complexes can also reasonably act as masked frustrated radical pairs (FRPs). FRP reactivity with the group VI Al/M complexes was achieved under photochemical conditions, producing unsaturated metal-carbonyl dimers [(CpCr)2(CO)3]2- and [Mn2(CO)8]2-, which would otherwise be unstable under standard conditions but that are isolable here due to Al(III) coordination. The metal-metal bonding in these unsaturated metal-carbonyl dimers was also analyzed theoretically.

Spin Dynamics of Radical Pairs Using the Stochastic Schrödinger Equation in MolSpin.

The chemical reactivity of radical pairs is strongly influenced by the interactions of electronic and nuclear spins. A detailed understanding of these effects requires a quantum description of the spin dynamics that considers spin-dependent reaction rates, interactions with external magnetic fields, spin-spin interactions, and the loss of spin coherence caused by coupling to a fluctuating environment. Modeling real chemical and biochemical systems, which frequently involve radicals with multinuclear spin systems, poses a severe computational challenge. Here, we implement a method based on the stochastic Schrödinger equation in the software package MolSpin. Large electron-nuclear spin systems can be simulated efficiently, with asymmetric spin-selective recombination reactions, anisotropic hyperfine interactions, and nonzero exchange and dipolar couplings. Spin-relaxation can be modeled using the stochastic time-dependence of spin interactions determined by molecular dynamics and quantum chemical calculations or by allowing rate coefficients to be explicitly time-dependent. The flexibility afforded by this approach opens new avenues for exploring the effects of complex molecular motions on the spin dynamics of chemical transformations.

Charge and Spin Dynamics and Destabilization of Shallow Nitrogen-Vacancy Centers under UV and Blue Excitation.

Shallow nitrogen-vacancy (NV) centers in diamond offer opportunities to study photochemical reactions, including photogeneration of radical pairs, at the single-molecule regime. A prerequisite is a detailed understanding of charge and spin dynamics of NVs exposed to the short-wavelength light required to excite chemical species. Here, we investigate the charge and spin dynamics of shallow NVs under 445 and 375 nm illumination. With blue excitation, charge-state preparation is power-dependent, and modest spin initialization fidelity is observed. Under UV excitation, charge-state preparation is power-independent and no spin polarization is observed. Aging of NVs under prolonged UV exposure manifests in a reduced charge stability and spin contrast. We attribute this aging to modified local charge environments of near-surface NVs and identify distinct electronic traps only accessible at short wavelengths. Finally, we evaluate the prospects of NVs to probe photogenerated radical pairs based on measured sensitivities and outline possible sensing schemes.

Photochemical Mechanism of Co-C Bond Activation via Triplet Energy Transfer in Ethyl(aqua)cobaloxime.

The photochemical decomposition of ethyl(aqua)cobaloxime, [EtCoIII(dmgH)2H2O], a vitamin B12 derivative model complex, was investigated to understand the mechanism of the Co-CEt bond scission induced by light. Upon irradiation of [EtCoIII(dmgH)2H2O], the Co-CEt bond undergoes homolytic scission, resulting in Et/Co(II) radical pair (RP) formation in a similar fashion observed in alkylcobalamins. The [EtCoIII(dmgH)2H2O] complex acts as a potent quencher of a wide variety of excited states in the presence of organic molecules such as benzophenone. It has been proposed that the reaction mechanism involves Dexter energy transfer, resulting in the bond dissociation process. Two issues associated with the proposed mechanism have been investigated, namely, (i) how the energy transfer occurs from benzophenone to cobaloxime and (ii) how the Co-CEt bond is activated and cleaved. Both TD-DFT and CASSCF/NEVPT2 methods have been applied to show the feasibility of the energy transfer reaction via the triplet pathway from photocatalyst to substrate.

The Effect of Spin Relaxation on Magnetic Compass Sensitivity in ErCry4a.

This study explores the impact of thermal motion on the magnetic compass mechanism in migratory birds, focusing on the radical pair mechanism within cryptochrome photoreceptors. The coherence of radical pairs, crucial for magnetic field inference, is curbed by spin relaxation induced by intra-protein motion. Molecular dynamics simulations, density-functional-theory-based calculations, and spin dynamics calculations were employed, utilizing Bloch-Redfield-Wangsness (BRW) relaxation theory, to investigate compass sensitivity. Previous research hypothesized that European robin's cryptochrome 4a (ErCry4a) optimized intra-protein motion to minimize spin relaxation, enhancing magnetic sensing compared to the plant Arabidopsis thaliana's cryptochrome 1 (AtCry1). Different correlation times of the nuclear hyperfine coupling constants in AtCry1 and ErCry4a were indeed found, leading to distinct radical pair recombination yields in the two species, with ErCry4a showing optimized sensitivity. However, this optimization is likely negligible in realistic spin systems with numerous nuclear spins. Beyond insights in magnetic sensing, the study presents a detailed method employing molecular dynamics simulations to assess for spin relaxation effects on chemical reactions with realistically modelled protein motion, relevant for studying radical pair reactions at finite temperature.

Detecting Chirality-Induced Spin Selectivity in Randomly Oriented Radical Pairs Photogenerated by Hole Transfer.

Chirality-induced spin selectivity (CISS) has the potential to control the spin dynamics of chiral molecules for applications in quantum information science. Here we investigate the effect of CISS on the spin dynamics of radical pair formation following photodriven hole transfer in a pair of donor-chiral bridge-acceptor (D-Bχ-A) enantiomers, where D = 2,2,6,6-tetramethyl[1,3]-dioxolo[4,5-f][1,3]benzodioxole, Bχ = (R)- or (S)-2,2'-dimethoxy-4,4'-diphenyl-5,5',6,6',7,7',8,8'-octahydro-1,1'-binaphthalene, and A = naphthalene-(1,4:5,8)-bis(dicarboximide). The results are compared to those obtained on the corresponding achiral D-B-A reference molecule in which B = 2″,3',5',6″-tetramethyl-1,1':4',1″:4″,1‴-quaterphenyl. Photoexcitation of A in a randomly oriented sample of D-Bχ-A in glassy butyronitrile at 85 K results in subnanosecond two-step hole transfer from 1*A to D to form D•+-Bχ-A•-, which was characterized using time-resolved electron paramagnetic resonance (TREPR) spectroscopy at X (9.6 GHz), Q (34 GHz), and W (94 GHz) bands. The spectra show line shape changes that are characteristic of a ∼38% contribution of CISS to the spin dynamics of D•+-Bχ-A•- formation. The line shape changes resulting from CISS are particularly apparent in the TREPR spectra at X-band as predicted by recent theory. These results show that (1) CISS has a significant influence on radical pair dynamics initiated by photodriven hole transfer, which is complementary to our recent electron transfer results, and (2) CISS can be detected using TREPR on radical pairs that are randomly oriented relative to an external magnetic field.

A Thermally Populated Germylene-Based Donor-Acceptor Diradical.

This work reports synthesis of a germylene based donor-acceptor molecule and its thermal excitation to a triplet state by coordination with a Lewis acid. Products have been characterized by single crystal X-ray diffraction, EPR spectroscopy, and SQUID measurement, in conjunction with DFT calculation. The singlet-triplet energy gap of the donor-acceptor molecule is dramatically reduced from -18.8 to -7.2 kcal/mol by the coordination with B(C6F5)3 (BCF), which enables an intramolecular single electron transfer from one germylene moiety to another upon heating, forming an intramolecular radical ion pair with diradical character. The work provides an approach to the formation of thermally populated open-shell species of heavier main group elements.

A Thermally Populated Germylene‐Based Donor‐Acceptor Diradical

This work reports synthesis of a germylene based donor‐acceptor molecule and its thermal excitation to a triplet state by coordination with a Lewis acid. Products have been characterized by single crystal X‐ray diffraction, EPR spectroscopy, and SQUID measurement, in conjunction with DFT calculation. The singlet‐triplet energy gap of the donor‐acceptor molecule is dramatically reduced from ‐18.8 to ‐7.2 kcal/mol by the coordination with B(C6F5)3 (BCF), which enables an intramolecular single electron transfer from one germylene moiety to another upon heating, forming an intramolecular radical ion pair with diradical character. The work provides an approach to the formation of thermally populated open‐shell species of heavier main group elements.

Low Magnetic Fields Stimulates Cardiac Mitochondrial Bioenergetics with a Bell-Shaped Response, Possibly Through the Radical Pair Mechanism

Low Magnetic Fields Stimulates Cardiac Mitochondrial Bioenergetics with a Bell-Shaped Response, Possibly Through the Radical Pair Mechanism

Photocatalytic high-effective removal and recovery of uranium induced by benzyl alcohol with low cost and environment-kind

Photocatalysis, one of the environment-friendly and efficient technology, showed application prospects on uranium removal and recovery in spite of the expensive photocatalysts. Herein, we reported a novel strategy induced by benzyl alcohol for photo-autocatalytic removal and recovery of uranium, which achieved excellent removal rate and avoided the dependence on photocatalysts. The results showed that, in slightly acidic environments, the uranium removal rate could achieve over 99 % under air within an hour illumination via the redox reaction of radical ion pair [UO2+, Ph·CHOH], which can be produced by the photoactivation of benzyl alcohol for the active benzylic C(sp3) − H bonds. At the same time, benzyl alcohol was selectively oxidized to benzaldehyde, an important industrial feed stock of significance in fine and chemical industries. Moreover, uranium could be removed to 186 ppb within 4 h of illumination, which was up to the emission standard proposed in GB 23727–2020. This strategy exhibited excellent removal performance upon solar illumination and recovered uranium with 99.08 % removal rate in the existence of heteroions, which indicated that our strategy has important application potential.