Radical-Pair-Based Magnetoreception Amplified by Radical Scavenging: Resilience to Spin Relaxation

This is the author accepted manuscript. The final version is available from American Chemical Society via the DOI in this record.Birds and several other species are equipped with the remarkable ability to sense the geomagnetic field for the purpose of navigation and orientation. The primary detection mechanism of this compass sense is uncertain but appears to originate from a truly quantum process involving spin-correlated radical pairs. In order to elicit sensitivity to weak magnetic fields, such as the Earth’s magnetic field, the underlying spin dynamics must be protected from fast decoherence. In this work, we elucidate the effects of spin relaxation on a recently suggested reaction scheme involving three radicals, instead of a radical pair, doublet-quartet interconversion under magnetic interactions, and a spin-selective scavenging reaction. We show that, besides giving rise to a vastly enhanced reaction anisotropy, this extended reaction scheme is more resilient to spin relaxation than the conventional radical pair mechanism. Surprisingly, the anisotropic magnetic field effect can be enhanced by fast spin relaxation in one of the radicals of the primary pair. We discuss this finding in the context of magnetoreception. Radical scavenging can protect the spin system against fast spin relaxation in one of the radicals, thereby providing a credible model to the involvement of fast relaxing radical pairs, such as FADH•/O2•–, in radical-pair based magnetoreception. This finding will help explain behavioral observations that seem incompatible with the previously proposed flavin semiquinone/tryptophanyl radical pair.The author is indebted to Prof. Peter Hore (University of Oxford) for continuous support and many stimulating discussions. This work was partly conceived during the author affiliation with the Hore group at the University of Oxford, where it was supported by the European Research Council (under the European Union’s seventh Framework Programme, FP7/2007-2013/ERC Grant Agreement No. 340451) and the Air Force Office of Scientific Research (Air Force Materiel Command, USAF award no. FA9550-14-1-0095). The author thanks Dr. Alex Jones (University of Manchester) for discussion of the scavenging mechanism in the context of magnetic field effects in D. melanogaster. The image of the robin used in the TOC graphic is extracted from a photograph by Artur Rydzewski, which is licensed under a Creative Commons Attribution 4.0 International License

F-cluster: Reaction-induced spin correlation in multi-radical systems

This is the final version. Available on open access from AIP Publishing via the DOI in this recordData availability: The data that support the findings of this study are available within the article and its supplementary material.We provide a theoretical analysis of spin-selective recombination processes in clusters of n ≥ 3 radicals. Specifically, we discuss how spin correlation can ensue from random encounters of n radicals, i.e., "F-clusters" as a generalization of radical F-pairs, acting as precursors of spin-driven magnetic field effects. Survival probabilities and the spin correlation of the surviving radical population, as well as transients, are evaluated by expanding the spin density operator in an operator basis that is closed under application of the Haberkorn recombination operator and singlet-triplet dephasing. For the primary spin cluster, the steady-state density operator is found to be independent of the details of the recombination network, provided that it is irreducible; pairs of surviving radicals are triplet-polarized independent of whether they are actually reacting with each other. The steady state is independent of the singlet-triplet dephasing, but the kinetics and the population of sister clusters of smaller size can depend on the degree of dephasing. We also analyze reaction-induced singlet-triplet interconversion in radical pairs due to radical scavenging by initially uncorrelated radicals ("chemical Zeno effect"). We generalize previous treatments for radical triads by discussing the effect of spin-selective recombination in the original pair and extending the analysis to four radicals, i.e., radical pairs interacting with two radical scavengers.Engineering and Physical Sciences Research Council (EPSRC)Leverhulme Trus

On the magnetosensitivity of lipid peroxidation: two- versus three-radical dynamics

This is the final version. Available on open access from the Royal Society of Chemistry via the DOI in this recordData availability: The datasets generated during the current study are available from the corresponding author on reasonable request.We present a theoretical analysis of the putative magnetosensitivity of lipid peroxidation. We focus on the widely accepted radical pair mechanism (RPM) and a recently suggested idea based on spin dynamics induced in three-radical systems by the mutual electron–electron dipolar coupling (D3M). We show that, contrary to claims in the literature, lipid peroxides, the dominant chain carriers of the autoxidation process, have associated non-zero hyperfine coupling interactions. This suggests that their recombination could, in principle, be magnetosensitive due to the RPM. While the RPM indeed goes a long way to explaining magnetosensitivity in these systems, we show that the simultaneous interaction of three peroxyl radicals via the D3M can achieve larger magnetic field effects (MFE), even if the third radical is remote from the recombining radical pair. For randomly oriented three-radical systems, the D3M induces a low-field effect comparable to that of the RPM. The mechanism furthermore immunizes the spin dynamics to the presence of large exchange coupling interactions in the recombining radical pair, thereby permitting much larger MFE at magnetic field intensities comparable to the geomagnetic field than would be expected for the RPM. Based on these characteristics, we suggest that the D3M could be particularly relevant for MFE at low fields, provided that the local radical concentration is sufficient to allow for three-spin radical correlations. Eventually, our observations suggest that MFEs could intricately depend on radical concentration and larger effects could ensue under conditions of oxidative stress.Engineering and Physical Sciences Research Council (EPSRC

Molecular dynamics simulations disclose early stages of the photo-Activation of cryptochrome 4 (article)

This is the final version. Available from IOP Publishing via the DOI in this record.The dataset associated with this article is in ORE: https://doi.org/10.24378/exe.363Birds appear to be equipped with a light-dependent, radical-pair-based magnetic compass that relies on truly quantum processes. While the identity of the sensory protein has remained speculative, cryptochrome 4 has recently been identified as the most auspicious candidate. Here, we report on all-Atom molecular dynamics (MD) simulations addressing the structural reorganisations that accompany the photoreduction of the flavin cofactor in the European robin cryptochrome 4 (ErCry4). Extensive MD simulations reveal that the photo-Activation of ErCry4 induces large-scale conformational changes on short (hundreds of nanoseconds) timescales. Specifically, the photo-reduction is accompanied with the release of the C-Terminal tail, structural rearrangements in the vicinity of the FAD-binding site, and the noteworthy formation of an α-helical segment at the N-Terminal part. Some of these rearrangements appear to expose potential phosphorylation sites. We describe the conformational dynamics of the protein using a graph-based approach that is informed by the adjacency of residues and the correlation of their local motions. This approach reveals densely coupled reorganisation entities, i.e. graph communities, which could facilitate an efficient signal transduction due to a high density of hubs. These communities are interconnected by a small number of highly important residues. The network approach clearly identifies the sites restructuring upon photo-Activation, which appear as protrusions or delicate bridges in the reorganisation network. We also find that, unlike in the homologous cryptochrome from D. melanogaster, the release of the C-Terminal domain does not appear to be correlated with the transposition of a histidine residue close to the FAD cofactor.Engineering and Physical Sciences Research Council (EPSRC)Royal SocietyLundbeck FoundationDanish Councils for Independent ResearchRussian Science Foundatio

Floquet theory of radical pairs in radiofrequency magnetic fields.

This is the final version of the article. Available from AIP Publishing via the DOI in this record.We present a new method for calculating the product yield of a radical pair recombination reaction in the presence of a weak time-dependent magnetic field. This method successfully circumvents the computational difficulties presented by a direct solution of the Liouville-von Neumann equation for a long-lived radical pair containing many hyperfine-coupled nuclear spins. Using a modified formulation of Floquet theory, treating the time-dependent magnetic field as a perturbation, and exploiting the slow radical pair recombination, we show that one can obtain a good approximation to the product yield by considering only nearly degenerate sub-spaces of the Floquet space. Within a significant parameter range, the resulting method is found to give product yields in good agreement with exact quantum mechanical results for a variety of simple model radical pairs. Moreover it is considerably more efficient than the exact calculation, and it can be applied to radical pairs containing significantly more nuclear spins. This promises to open the door to realistic theoretical investigations of the effect of radiofrequency electromagnetic radiation on the photochemically induced radical pair recombination reactions in the avian retina which are believed to be responsible for the magnetic compass sense of migratory birds.We gratefully acknowledge funding from the European Research Council under the European Union’s 7th Framework Programme, FP7/2007-2013/ERC Grant Agreement No. 340451, and from the US Air Force (USAF) Office of Scientific Research under the Air Force Materiel Command, USAF Award No. FA9550-14-1-0095

Radical Scavenging Could Answer the Challenge Posed by Electron-Electron Dipolar Interactions in the Cryptochrome Compass Model

This is the final version. Available on open access from the American Chemical Society via the DOI in this recordData availability: The numerical data that this study has generated are available from the authors upon request.Many birds are endowed with a visual magnetic sense that may exploit magnetosensitive radical recombination processes in the protein cryptochrome. In this widely accepted but unproven model, geomagnetic sensitivity is suggested to arise from variations in the recombination rate of a pair of radicals, whose unpaired electron spins undergo coherent singlet-triplet interconversion in the geomagnetic field by coupling to nuclear spins via hyperfine interactions. However, simulations of this conventional radical pair mechanism (RPM) predicted only tiny magnetosensitivities for realistic conditions because the RPM's directional sensitivity is strongly suppressed by the intrinsic electron-electron dipolar (EED) interactions, casting doubt on its viability as a magnetic sensor. We show how this RPM-suppression problem is overcome in a three-radical system in which a third "scavenger" radical reacts with one member of the primary pair. We use this finding to predict substantial magnetic field effects that exceed those of the RPM in the presence of EED interactions in animal cryptochromes.UK Defence Science and Technology LaboratoryOffice of Naval Research (ONR)Engineering and Physical Sciences Research Council (EPSRC

Magnetic Field-Sensitive Radical Pair Dynamics in Polymethylene Ether-Bridged Donor–Acceptor Systems

This is the final version of the article. Available from American Chemical Society via the DOI in this record.Donor–acceptor systems forming exciplexes are versatile models for the study of magnetic field effects (MFEs) on charge recombination reactions. The MFEs originate from singlet–triplet interconversion within transient radical ion pairs (RIPs), which exist in a dynamic equilibrium with the exciplexes. Here, we describe the synthesis and MFEs of the chain-linked N,N-dimethylaniline (DMA)/9-methylanthracene (MAnt) donor–acceptor system MAnt–(CH2)n–O–CH2–CH2–DMA for n = 6, 8, 10, and 16. The MFEs are found to increase with increasing chain length. Effects as large as 37.5% have been observed for the long-chain compound with n = 16. The solvent dependence of the MFEs at magnetic field intensity 75 mT is reported. For the range of solvent static dielectric constants εs = 6.0–36.0, the MFEs go through a maximum for intermediate polarities, for which the direct formation of RIPs prevails and their dissociation and reencounter are balanced. Field-resolved measurements (MARY spectra) are reported for solutions in butyronitrile. The MARY spectra reveal that for n = 8, 10, 16, the average exchange interaction is negligible during the coherent lifetime of the radical pair. However, singlet–triplet dephasing broadens the lineshape; the shorter the linker, the more pronounced this effect is. For n = 6, a dip in the fluorescence intensity reveals a nonzero average exchange coupling of the order of ±5 mT. We discuss the field-dependence in the framework of the semiclassical theory taking spin-selective recombination, singlet–triplet dephasing, and exchange coupling into account. Singlet recombination rates of the order of 0.1 ns–1 and various degrees of singlet–triplet dephasing govern the spin dynamics. In addition, because of a small free energy gap between the exciplex and the locally excited fluorophore quencher pair, a fully reversible interconversion between the RIP, exciplex, and locally excited fluorophore is revealed by spectrally resolved MFE measurements for the long-chain systems (n = 10, 16).The financial support from The Royal Society (RG170378), Ho Chi Minh City University of Technology and Education (T2018-36TD̵) and Austrian Science Fund (FWF-Project P ACS Omega Article DOI: 10.1021/acsomega.8b01232 ACS Omega 2018, 3, 10296−10305 10303 21518-N19) is gratefully acknowledged. D.R.K. is thankful NVIDIA for supporting this research through their GPU Grant Program

Monte-Carlo wavefunction approach for the spin dynamics of recombining radicals

This is the final published version; available from IOP Publishing via the DOI in this record.We adapt the Monte-Carlo wavefunction (MCWF) approach to treat the open-system spin dynamics of radical pairs subject to spin-selective recombination reactions. For these systems, nonLindbladian master equations are widely employed, which account for recombination via the non trace-preserving Haberkorn superoperator in combination with reaction-dependent exchange and singlet-triplet dephasing terms. We show that this type of master equation can be accommodated in the MCWF approach, by introducing a second type of quantum jump that accounts for the reaction simply by suitably terminating the propagation. In this way, we are able to evaluate approximate solutions to the time-dependent radical pair survival probability for systems that have been considered untreatable with the master equation approach until now. We explicate the suggested approach with calculations for radical pair reactions that have been suggested to be relevant for the quantum compass of birds and related phenomena.Engineering and Physical Sciences Research Council (EPSRC

Electron-Electron Dipolar Interaction Poses a Challenge to Radical Pair Mechanism of Magnetoreception

This is the final version. Available on open access from the American Chemical Society via the DOI in this recordA visual magnetic sense in migratory birds has been hypothesized to rely on a radical pair reaction in the protein cryptochrome. In this model, magnetic sensitivity originates from coherent spin dynamics, as the radicals couple to magnetic nuclei via hyperfine interactions. Prior studies have often neglected the electron–electron dipolar (EED) coupling from this hypothesis. We show that EED interactions suppress the anisotropic response to the geomagnetic field by the radical pair mechanism in cryptochrome and that this attenuation is unlikely to be mitigated by mutual cancellation of the EED and electronic exchange coupling, as previously suggested. We then demonstrate that this limitation may be overcome by extending the conventional model to include a third, nonreacting radical. We predict that hyperfine effects could work in concert with three-radical dipolar interactions to tailor a superior magnetic response, thereby providing a new principle for magnetosensitivity with applications for sensing, navigation, and the assessment of biological magnetic field effects.Engineering and Physical Sciences Research Council (EPSRC

Radical triads, not pairs, may explain effects of hypomagnetic fields on neurogenesis.

This is the final version. Available from Public Library of Science via the DOI in this record. Data Availability: All relevant data are within the manuscript and its Supporting information files.Adult hippocampal neurogenesis and hippocampus-dependent cognition in mice have been found to be adversely affected by hypomagnetic field exposure. The effect concurred with a reduction of reactive oxygen species in the absence of the geomagnetic field. A recent theoretical study suggests a mechanistic interpretation of this phenomenon in the framework of the Radical Pair Mechanism. According to this model, a flavin-superoxide radical pair, born in the singlet spin configuration, undergoes magnetic field-dependent spin dynamics such that the pair's recombination is enhanced as the applied magnetic field is reduced. This model has two ostensible weaknesses: a) the assumption of a singlet initial state is irreconcilable with known reaction pathways generating such radical pairs, and b) the model neglects the swift spin relaxation of free superoxide, which abolishes any magnetic sensitivity in geomagnetic/hypomagnetic fields. We here suggest that a model based on a radical triad and the assumption of a secondary radical scavenging reaction can, in principle, explain the phenomenon without unnatural assumptions, thus providing a coherent explanation of hypomagnetic field effects in biology.Engineering and Physical Sciences Research CouncilEngineering and Physical Sciences Research CouncilUK Defence Science and Technology LaboratoryOffice of Naval ResearchLeverhulme Trus