Biochemical systems make extensive use of chemically fueled processes (e.g., using ATP), but analogous abiotic systems remain rare. A key challenge is the identification of transformations that can be adapted to a range of applications and make use of readily available chemical fuels. In this context, the generation of transient covalent bonds is a fundamental tool for nonequilibrium systems chemistry. Here, we show that carbodiimides constitute a simple class of chemical fuels for dissipative assembly, taking advantage of their known reactivity to produce (hydrolytically unstable) anhydrides from carboxylic acids in water. Both aliphatic and aromatic anhydrides are formed on convenient time scales using the common, commercially available peptide coupling agent 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide (EDC). An important feature of this reaction is that no part of the carbodiimide is incorporated into the transient species; that is, the fuel is decoupled from the structure-and thus function-of the assembled state. We show that intramolecular anhydride formation of oligo(ethylene glycol) diacids gives macrocycles analogous to crown ethers, representing minimal examples of out-of-equilibrium supramolecular hosts. The kinetics and yields of macrocycle formation respond to cation guests, with the presence of matched cations decreasing their overall production.

Scheme 8. Fletcher's combination of nonequilibrium assembly and autocatalysis.Scheme 9. Guan's transient hydrogel generated by thiol oxidation.

Structure-property Effects in the Generation of Transient Aqueous Benzoic Acid Anhydrides by Carbodiimide Fuels. ChemRxiv. Preprint.

Scheme 8. Fletcher's combination of nonequilibrium assembly and autocatalysis.Scheme 9. Guan's transient hydrogel generated by thiol oxidation.

Transient changes in molecular geometry are key to the function of many important biochemical systems. Here, we show that diphenic acids undergo out-of-equilibrium changes in dihedral angle when reacted with a carbodiimide chemical fuel. Treatment of appropriately functionalized diphenic acids with EDC (N-(3-(dimethylamino)propyl)-N′-ethylcarbodiimide hydrochloride) yields the corresponding diphenic anhydrides, reducing the torsional angle about the biaryl bond by ∼45°, regardless of substitution. In the absence of steric resistance, the reaction is well-described by a simple mechanism; the resulting kinetic parameters can be used to derive important properties of the system, such as yields and lifetimes. The reaction tolerates steric hindrance ortho to the biaryl bond, although the competing formation of (transient) byproducts complicates quantitative analysis.