Quantum Dynamics of Radical Pairs Reactions in Membranes: Elucidating Magnetic Field Effects in Lipid Autoxidation

Lead Research Organisation: University of Exeter
Department Name: Physics

Abstract

Radicals are ubiquitous short-lived reaction intermediates that contain a single unpaired electron and are usually created in pairs in a well-defined electronic spin state, either singlet ("anti-parallel spins") or triplet ("parallel spins"). For chemical reactions involving such pairs of radicals, quantum effects can induce a remarkable sensitivity to the intensity and/or orientation of external static magnetic fields as weak as the Earth's magnetic field. The underlying mechanism, the so-called Radical Pair Mechanism, has attracted widespread interest from the scientific community and general audiences owing to its putative relevance to animal magnetoreception and possibly adverse effects of weak electromagnetic fields on human health. Indeed, a multitude of studies have suggested an association between weak magnetic field exposure and increased levels of oxidative stress, genotoxic effects and apoptosis/necrosis. While detailed interaction models are still lacking - a factor that severely impedes the assessment of partly controversial literature on this subject and the advancement of guidelines for magnetic field exposure - the oxidative degradation of phospholipids appears as an overarching motif in many exposure studies. Indeed, reactive oxygen species and the free radicals they induce are known to attack polyunsaturated fatty acids in phospholipid membranes, thereby initiating lipid peroxidation reactions, which alter membrane characteristics and induce cell damage. Through termination and degenerate chain branching steps of this free-radical chain reaction, magnetosensitivity is feasibly imparted. Unfortunately, mechanistic details and a sound theoretical understanding of these effects are still lacking: the Radical Pair Mechanism has not yet been developed for systems confined to two dimensions, such as lipid bilayers, and the properties of the involved radicals have not been characterized with respect to magnetosensitive pathways and spin relaxation.

Here, I propose a theoretical and computational investigation of intricacies of the radical pair mechanism at two-dimensional interfaces and the exploration of related amplification mechanisms beyond the standard Radical Pair Mechanism that I have recently suggested in the field of magnetoreception, but which are utterly unexplored in this context. In particular, I will focus on:

a) the effect of confining the diffusion of coupled radical pairs to two dimensions,

b) the potential for molecular motion to result in noise-enhanced magnetic field effects (MFEs), and

c) the so-called chemical Zeno effect, by which MFEs are amplified by scavenging reactions with spin-carrying reaction partners.

I envisage to find support for the hypothesis that unexpectedly large MFEs could ensue in these confined systems, intrinsically and as a consequence of the abovementioned secondary amplification effects. In addition to providing a better, more complete understanding of MFEs, our work will also reveal how subtle quantum effects can be sustained and amplified in noisy environments. These insights are essential to the emerging field of Quantum Biology and could pave the way to enhanced quantum devices and sensors with improved resilience to environmental noise. Furthermore, if such amplification schemes are found to apply to biologically relevant reactions, it could prompt a reassessment of the health risks of weak magnetic field exposure and future research into the use of MFEs as therapeutics to boost the immune response via the radical pair mechanism.

Abbreviations: MFE = Magnetic Field Effect; RPM = Radical Pair Mechanism.

Planned Impact

This proposal addresses topics of fundamental research. I will provide novel theoretical and computational tools for radical pair reactions in two-dimensional confined systems, suggest (quantum) amplification pathways, elucidate mechanisms for maintaining quantum coherences in a noisy environment, and develop a sound theoretical model for the interpretation of biological effects of magnetic field exposure in general and those related to oxidative stress and lipid autoxidation in particular. These activities will provide immediate benefits in the academic and industrial research context and, in the long run, economic and societal benefits.

Economical and industrial impacts:
As radical species (e.g. superoxide) are an integral part of the immune response, MFEs on free radical recombination reactions could be of therapeutic use. Indeed, recent studies suggest that static magnetic fields can enhance the effects of antineoplastic drugs on cancer cells (probably by altering the cell membrane permeability and, possibly, Ca2+ influx). By providing an understanding of how MFEs function at membranes on the quantum and molecular level, this proposal will support the development of a new branch of non-invasive therapy, i.e. magnetoceuticals, which will be aimed at utilizing the effect of magnetic fields on radical pair dynamics for the benefit of human health. I anticipate that my ideas will impact upon the healthcare and pharmaceutical industry and lay the foundations for spin-out companies and intellectual property activity, thereby contributing to revived economic growth.
In addition, with the focus on establishing the theoretical foundation for amplification and decoherence protection of MFEs, my work will support an emerging innovation eco-system that extends far beyond the abovementioned healthcare sector. With an understanding of how feeble quantum effects can be sustained in noisy biological environments, we could build quantum devices that are much less at the mercy of decoherence than current designs. This would have tremendous impact on fields such as quantum information processing and sensing and spintronics. In addition, MFEs could be employed to control/enhance charge recombination/separation quantum yields, improving the efficiency of e.g. organic light emitting diodes and some organic photovoltaic cells.

Advising and influencing into policy making:
I expect to reach policy makers and regulatory bodies by providing the impetus for a reassessment of exposure studies and safety regulations on weak magnetic field exposure and anthropogenic electromagnetic emissions, thereby promoting the preservation and improvement of public health and animal wellbeing. Currently the lack of a rigorous mechanistic cause-and-effect chain hampers further activity. While the focus here is on radical pair reactions at membranes, our results will also yield transferable insights to the ongoing debate on whether electromagnetic fields can disturb human regulatory mechanisms in a presently unknown way (e.g. via radical pair reactions of the circadian regulator cryptochrome).

Societal impacts:
This project also impacts on society in ways that are less tangible but which nonetheless will contribute to future prosperity. Firstly, through our efforts a sharper public awareness of the significance of subtle quantum effects for physiological processes in living organisms, as well as for technology, will be established. Secondly, students and future academics acquainted with this project will acquire a deep understanding of quantum mechanics, spin chemistry and applied mathematics, which will qualify them as shapers of the Quantum Age, be it in quantum computing, communication or Quantum Biology. With quantum effects expected to revolutionise technological processes and manufacturing, these qualifications, as well as public awareness, will not only be relevant in underpinning a future academic career but also in the industrial context.

Publications

10 25 50
 
Description We have identified a new kind of magnetic field effect that originates from the magnetic interaction of three or more radicals. This mechanism provides a new pathway to magnetosensitive chemical reactions that is complimentary to the established radical pair mechanism. Interestingly, the new effect can give rise to spiky features in the magnetic field dependence of reaction yields, which could be relevant for the assessment of the effects of weak magnetic fields (such as those generated by household appliances) on biological systems. This effect appears to be particularly relevant for the magnetosensitivity of lipid autoxidation reactions, which is the core question of this research proposal. In fact, our recent model calculations show that the new mechanism surpasses the effects predicted by the radical pair mechanism, thus suggesting that, surprisingly, it provides the predominant magnetosensitive pathway.
Exploitation Route We have so far laid out the theoretical fundamentals. We are now in the process to apply the idea to more realistic models of lipid autoxidation, with the aim to predict the magnetic field dependence of the effect. This will provide new insights and understanding essential for the assessment of health risks associated with the exposure to weak electromagnetic fields.
Sectors Environment,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description We have engaged in public outreach projects, shaped the public opinion and influenced policy makers through scientific presentations. Details have been laid out in the specific summaries.
Sector Environment,Healthcare
Impact Types Societal,Policy & public services

 
Title New model of magnetosensitivity in three-radical systems 
Description The Radical Pair Mechanism is a canonical model for the magnetosensitivity of chemical reaction processes. The key ingredient of this model is the hyperfine interaction that induces a coherent mixing of singlet and triplet electron spin states in pairs of radicals, thereby facilitating magnetic field effects (MFEs) on reaction yields through spin-selective reaction channels. We have developed an alternative model that demonstrates that the hyperfine interaction is not a categorical requirement to realize the sensitivity of radical reactions to weak magnetic fields. In systems comprising three instead of two radicals, dipolar interactions provide an alternative pathway for MFEs. 
Type Of Material Computer model/algorithm 
Year Produced 2018 
Provided To Others? Yes  
Impact Our model furthers the current understanding of the effects of weak magnetic fields on chemical reactions, could pave the way to a clearer understanding of the mysteries of magnetoreception and other biological MFEs and motivate the design of quantum sensors. 
 
Description Molecular dynamics simulations to inform spin dyanamic calculations 
Organisation University of Southern Denmark
Country Denmark 
Sector Academic/University 
PI Contribution Our research team has contributed a new graph based analysis of structural changes observed in long-time molecular dynamic trajectories and principal component analysis. We have also generated new molecular dynamics data based on protocols provided by our partners at the University of Southern Denmark.
Collaborator Contribution We have partnered with the group of Prof. Ilia A. Solov'yov to infer dynamics properties from molecular dynamics data. The Solov'yov group has contributed with computational resources (~£15.3k in-kind contribution) and intellectual input. In particular, they have provided molecular dynamics parametrisations of lipid radicals and molecular dynamics data for the dark state of cryptochrome 4 from the European robin.
Impact We have so far published a joint publication and are working towards further publications.
Start Year 2018
 
Title A framwork for spin dynmaics calculations of n radicals 
Description We have develop a versatile Python framework for the simulation of magnetic field effects resulting from the interaction of several, i.e. more than two, radicals. The program solves the Liouville von-Neumann equation of the spin density operator, augmented by terms accounting for the chemical reactivity and decoherence processes. The program is completely general and, for the first time, allows the simulation of magnetic field effects originating from the interaction of more than two radicals. It is delightfully user-friendly and also comes with a detailed manual. 
Type Of Technology Software 
Year Produced 2018 
Impact This program is essential for the realization of this research project, as it provides us with a versatile simulation platform that underpins our research. It has not yet been released to the public domain as we are in the process of expanding its scope and optimizing the underlying numerical methods. We plan to release the program subject to an open source license in the near future. 
 
Description Open day activities 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact We delivered an interactive presentation aimed at undergraduate students and the general public at the University of Exeter to disseminate our research and enhance the accessibility for non-experts. Approximately 20 % of the audience comprised members of the general public. We believe to have enticed our listeners and received positive feedback.
Year(s) Of Engagement Activity 2018,2019
 
Description Pint of Science 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact A presentation on magnetic field effects due to radical pair reactions has been delivered by Robert Keens, a PhD student working on three-radical effects, to an audience comprising mainly members from the general public at a Pint of Science event in Exeter. Pint of Science is a science festival that aims to communicate contemporary scientific developments to the public in an interesting, engaging and approachable way by bringing scientists to the pub and other accessible places.
Year(s) Of Engagement Activity 2019