Network control theory governs isomerization, chemists say

Network control theory can describe the photochemical isomerization of glucose to allose. This transformation, in which the hydroxy group on a single carbon flips from one stereochemical configuration to the other, seems like a simple epimerization, but the reaction is quite complicated. The chemists who did the work hope others will also use network control theory to better understand chemical transformations (Science 2024, DOI: 10.1126/science.adp2447).

In 2020, Massachusetts Institute of Technology chemistry professor Alison E. Wendlandt reported a reaction that converts the common sugar glucose into the rare sugar allose. Her team tried conventional approaches, like density functional theory and kinetic experiments, to understand why the reaction was selective only for one hydroxy group and didn’t epimerize the hydroxy groups on adjacent carbons. But they failed.

So Wendlandt and coworkers teamed up with Merck & Co.’s Eugene E. Kwan to get a better handle on what was happening. They found that “what appears to be a reaction of a single molecule at a single site actually turns out to be a complex dynamic and continuously evolving network of 8 different sugar isomers connected by 12 different reactions in a process overall that is governed by 48 different rate constants,” Wendlandt says.

Robert R. Knowles, who studies asymmetric catalysis at Princeton University and was not involved in the work, says in an email that “this work will help inspire new ways of thinking about complex dynamics in stereoselective synthesis and beautifully highlights how excited-state mechanisms can enable unconventional modes of selectivity that simply aren’t possible in ground-state chemistry.”