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.