Molecular Origins of Simultaneous Chemo‑, Enantio‑, and Substrate Selectivity in Non-Natural Photoenzymatic Radical Reactions
Felipe Curtolo, Sijia S. Dong
TL;DR
This paper explains how a special enzyme can control three types of chemical selectivity in radical reactions through a newly discovered preactivation step and electronic state interactions.
Contribution
The study reveals a new preactivation mechanism and electronic state dynamics that enable triple selectivity in photoenzymatic reactions.
Findings
Triple selectivity in photoenzymatic reactions is governed by reaction-level mechanisms, not binding preferences.
A previously unknown preactivation step involving bond elongation is essential for productive photochemistry.
Chemoselectivity is controlled by conical intersection dynamics between electronic states.
Abstract
Selective radical chemistry poses fundamental challenges for modern catalysis. Non-natural photoenzymes, most prominently flavin-dependent “ene”-reductases, have recently emerged as appealing systems to address these challenges by offering unmatched control over chemo-, enantio-, and substrate selectivity, yet their underlying photocatalytic mechanisms remain unclear. Here, we reveal the complete molecular basis of the triple selectivity control in the photoenzymatic radical reactions by the flavin-dependent “ene”-reductase GkOYE-G7 through computational simulations based on multiscale multireference-quantum-mechanics/molecular-mechanics modeling and bias-exchange metadynamics. Our findings demonstrate that control emerges from reaction-level mechanisms rather than binding preferences. We discover that productive photochemistry requires a previously unknown preactivation step involving…
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Taxonomy
TopicsRadical Photochemical Reactions · Metal-Catalyzed Oxygenation Mechanisms · Advanced oxidation water treatment