Computational Evidence for Kinetically Controlled Radical Coupling during Lignification

Lignin
is an alkyl–aromatic biopolymer that, despite its
abundance, is underutilized as a renewable feedstock because of its
highly complex structure. An approach to overcome this challenge that
has gained prominence in recent years leverages the plasticity and
malleability of lignin biosynthesis to tune lignin structure in planta
through genetic approaches. An improved understanding of lignin biosynthesis
can thus provide fundamental insights critical for the development
of effective tailoring and valorization strategies. Although it is
widely accepted that lignin monomers and growing chains are oxidized
enzymatically into radicals that then undergo kinetically controlled
coupling in planta, direct experimental evidence has been scarce because
of the difficulty of exactly replicating in planta lignification conditions.
Here, we computationally investigate a set of radical reactions representative
of lignin biosynthesis. We show that, contrary to the notion that
radical coupling reactions are usually barrierless and dynamically
controlled, the computed activation energies can be qualitatively
consistent with key structural observations made empirically for native
lignin in a variety of biomass types. We also rationalize the origins
of regioselectivity in coupling reactions through structural and activation
strain analyses. Our findings lay the groundwork for first-principles
lignin structural models and more detailed multiscale simulations
of the lignification process.

木质素（Lignin）是一类烷基芳香族生物聚合物，尽管其天然储量丰富，却因其结构极为复杂而未被充分开发为可再生原料。近年来，一种备受关注的解决方案利用了木质素生物合成的可塑性与延展性，通过遗传手段在植物体内调控木质素结构。因此，对木质素生物合成的深入理解，可为开发高效的定制化改性与增值利用策略提供至关重要的基础认知。
尽管学界已普遍认可，木质素单体与生长中的链段会经酶促氧化生成自由基，随后在植物体内以动力学控制的方式发生偶联反应，但由于难以精准复刻植物体内的木质化过程条件，直接的实验证据一直较为匮乏。
本研究通过计算方法研究了一组代表木质素生物合成过程的自由基反应。我们的研究表明，与“自由基偶联反应通常无势垒且由动力学控制”的普遍认知相悖，计算得到的活化能可与多种生物质中天然木质素的经验性关键结构观测结果定性吻合。此外，我们通过结构与活化应变分析，阐明了偶联反应区域选择性的起源。本研究的发现为基于第一性原理的木质素结构模型，以及更为精细的木质化过程多尺度模拟奠定了基础。