Endergonic synthesis driven by chemical fuelling

08 November 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Spontaneous chemical reactions proceed energetically downhill to either a local or global minimum, limiting possible transformations to those that are exergonic. Endergonic reactions do not proceed spontaneously and require an input of energy. Light has been used to drive a number of deracemisations and thermodynamically unfavourable bond-forming reactions, but is restricted to substrates that can absorb, directly or indirectly, energy provided by photons. In contrast, anabolism involves energetically uphill transformations powered by chemical fuels. Here we report on the transduction of energy from an artificial chemical fuel to drive a thermodynamically unfavourable Diels–Alder reaction. Carboxylic acid catalysed carbodiimide-to-urea formation is chemically orthogonal to the reaction of the diene and dienophile, but transiently brings the functional groups into close proximity, causing the otherwise prohibited cycloaddition to proceed in modest (12%) yield and with high levels of regio- (>99%) and stereoselectivity (92:8 exo:endo). At the chemically fuelled steady state, kinetic asymmetry in the fuelling cycle ratchets the Diels–Alder reaction away from the equilibrium distribution of the Diels–Alder:retro-Diels–Alder products. The driving of the endergonic reaction away from equilibrium occurs through a ratchet mechanism, reminiscent of how molecular machines directionally bias motion. Ratcheting synthesis has the potential to expand the synthetic chemistry toolbox, offering new paradigms in reactivity, complexity and control.

Keywords

endergonic
fuelling
non-equilibrium
chemostatting
orthogonal
ratchet
dissipative
Diels-Alder
systems chemistry
supramolecular chemistry
reaction mechanisms
kinetics

Supplementary materials

Title
Description
Actions
Title
Supplementary Information for Endergonic Synthesis driven by Chemical Fuelling
Description
Supplementary Information containing a detailed description of how experiments were carried out, and some additional analysis for interested readers
Actions

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.