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

膜中自由基对反应的量子动力学：阐明脂质自氧化中的磁场效应

• 批准号: EP/R021058/1
• 负责人: Daniel Kattnig
• 金额: $ 12.88万
• 依托单位: UNIVERSITY OF EXETER
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FR021058%2F1
• 关键词: Quantum; Dynamics; Radical; Pairs; Reactions

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), andc) 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.

自由基是普遍存在的短寿命反应中间体，含有单个不成对的电子，通常以明确的电子自旋状态成对产生，可以是单线态（“反平行自旋”）或三线态（“平行自旋”）。对于涉及此类自由基对的化学反应，量子效应可以引起对与地球磁场一样弱的外部静磁场的强度和/或方向的显着敏感性。其基本机制，即所谓的自由基对机制，由于其与动物磁感受的假定相关性以及弱电磁场可能对人类健康产生的不利影响而引起了科学界和普通观众的广泛兴趣。事实上，大量研究表明，弱磁场暴露与氧化应激、基因毒性效应和细胞凋亡/坏死水平升高之间存在关联。虽然仍然缺乏详细的相互作用模型（这一因素严重阻碍了对有关该主题的部分有争议文献的评估以及磁场暴露指南的进步），但磷脂的氧化降解似乎是许多暴露研究中的首要主题。事实上，已知活性氧及其诱导的自由基会攻击磷脂膜中的多不饱和脂肪酸，从而引发脂质过氧化反应，从而改变膜特性并诱导细胞损伤。通过该自由基链式反应的终止和简并链支化步骤，可以可行地赋予磁敏感性。不幸的是，仍然缺乏对这些效应的机制细节和合理的理论理解：尚未针对仅限于二维的系统（例如脂质双层）开发自由基对机制，并且尚未对所涉及自由基的性质进行表征在这里，我提出了对二维界面上自由基对机制复杂性的理论和计算研究，以及对我最近研究的标准自由基对机制之外的相关放大机制的探索在磁接收领域提出了这一建议，但在这方面还完全没有被探索过。我将特别关注：a）将耦合自由基对的扩散限制在二维的效应，b）分子运动导致噪声增强磁场效应（MFE）的潜力，以及c）所谓的化学芝诺效应，通过这种效应，MFE 通过与自旋携带反应伙伴的清除反应而被放大。我设想为以下假设找到支持：在这些受限系统中，本质上和由于以下原因，可能会出现意想不到的大 MFE上述二次放大效应。除了提供对 MFE 更好、更完整的理解之外，我们的工作还将揭示如何在嘈杂的环境中维持和放大微妙的量子效应。这些见解对于新兴的量子生物学领域至关重要，并且可以为增强量子设备和传感器铺平道路，提高对环境噪声的适应能力。此外，如果发现这种放大方案适用于生物学相关反应，它可能会促使人们重新评估弱磁场暴露的健康风险，并促进未来研究使用 MFE 作为通过自由基对机制增强免疫反应的疗法。缩写：MFE = 磁场效应； RPM = 激进配对机制。

项目成果

Molecular dynamics simulations disclose early stages of the photo-activation of cryptochrome 4

分子动力学模拟揭示了隐花色素 4 光激活的早期阶段

• DOI: http://dx.10.1088/1367-2630/aad70f
• 发表时间: 2018
• 期刊: New Journal of Physics
• 影响因子: 3.3
• 作者: Kattnig D

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

电子-电子偶极相互作用对磁接收的自由基对机制提出了挑战。

• DOI: http://dx.10.1021/acs.jpclett.0c00370
• 发表时间: 2020
• 期刊: The journal of physical chemistry letters
• 作者: Babcock NS

Modeling spin relaxation in complex radical systems using MolSpin.

使用 MolSpin 对复杂自由基系统中的自旋弛豫进行建模。

• DOI: http://dx.10.1002/jcc.27120
• 发表时间: 2023
• 期刊: Journal of computational chemistry
• 影响因子: 3
• 作者: Gerhards L

Molecular dynamics simulations disclose early stages of the photo-activation of cryptochrome 4

分子动力学模拟揭示了隐花色素 4 光激活的早期阶段

• DOI: http://dx.10.1101/324962
• 发表时间: 2018
• 作者: Kattnig D

On the optimal relative orientation of radicals in the cryptochrome magnetic compass

隐色磁罗经中自由基的最佳相对方位研究

• DOI: http://dx.10.1063/1.5115445
• 发表时间: 2019
• 期刊: The Journal of Chemical Physics
• 作者: Atkins C