Endergonic synthesis driven by chemical fuelling

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 deracemizations 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 yield (15% after two fuelling cycles) and with high levels of regio- (>99%) and stereoselectivity (92:8 exo:endo). 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 occurs through a ratchet mechanism (an energy or information ratchet, depending on the synthetic protocol), reminiscent of how molecular machines directionally bias motion. Ratcheting synthesis has the potential to expand the synthetic chemistry toolbox in terms of reactivity, complexity and control.

A Minimalistic Covalent Bond‐Forming Chemical Reaction Cycle that Consumes Adenosine Diphosphate

“…ADP hydrolysis) as part of a forward or backward pathway) and can be used to help realise a kinetically asymmetric reaction network and hence an information ratchet mechanism. [9][10][11][12][13][14] Kinetic modelling: A transient increase in concentration of 3 was seen upon addition of ADP, however it was unknown whether this was the result of a kinetically controlled driven system (Class 4) with consequent energy storage, [10,30,40] or a thermodynamically controlled adaptation of the system towards a changing ADP concentration, with all species equilibrated according to the concentration of templating anions (Class 3). [2] Compared with biochemical reaction networks, [4,39] fuelled self-assembly processes and other artificial responsive systems, [17,18,27,[19][20][21][22][23][24][25][26] the present reaction system is relatively simple, making it well suited to quantification of reaction parameters.…”

“…[2,13,[17][18][19][20][21][22][23][24][25][26][27] However, despite the fact that numerous 'fuelled' systems have now been reported, it has hitherto proven difficult, outside of the context of molecular pumps, [28,29] to understand whether the energy released from the fuel-to-waste reaction is effectively (partially) stored in the system. [30] It can be very difficult to tell whether altered concentrations of network components in response to a stimulus indicate a kinetically controlled non-equilibrium state (Class 4) or a thermodynamically controlled equilibrated adaption (Class 3). This analysis is hampered by the complexity that originates from the numerous kinetic parameters that govern such cycles.…”

Dynamic Promotion of the Oxygen Evolution Reaction via Programmable Metal Oxides

“…While this may seem like an error in our model, the overall reaction free energy change does not necessarily dictate the net reaction direction if the reaction coordinate changes with time . In fact, artificial molecular ratchets have been designed to drive endergonic reactions by coupling to an orthogonal energy source (one which does not impact the reaction coordinate of interest, but instead provides energy to drive the uphill reaction by, e.g., switching between potential energy surfaces with different local minima and maxima to directionally ratchet molecules). − Programmable catalysts are an “energy ratchet” where the work from an external oscillating stimulus enables chemical transformations not possible by conventional methods, such as supra-equilibrium conversion , and imparting significant net turnover into a closed catalytic loop …”