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

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.

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.