Structure–property Effects in the Generation of Transient Aqueous Benzoic Acid Anhydrides by Carbodiimide Fuels

Abstract

<div>The design of dissipative systems, which operate out-of-equilibrium by consuming chemical fuels, is challenging. As yet, there are few examples of privileged fuel chemistries that can be broadly applied in abiotic systems in the same way that ATP hydrolysis is exploited throughout biochemistry. The key issue is that designing nonequilibrium systems is inherently about balancing the relative rates of coupled reactions. The use of carbodiimides as fuels to generate transient aqueous carboxylic anhydrides has recently been used in examples of new nonequilibrium materials and supramolecular assemblies. Here, we explore the kinetics of formation and decomposition of a series of benzoic anhydrides generated from the corresponding acids and EDC under typical conditions (EDC = <i>N</i>-(3-dimethylaminopropyl)-<i>N</i>′-ethylcarbodiimide hydrochloride). The reactions can be described by a simple mechanism that merges known behavior for the two processes independently. Structure–property effects in these systems are dominated by differences in anhydride decomposition rate. The kinetic parameters allow trends in concentration-dependent properties to be simulated, such as reaction lifetimes, peak anhydride concentrations, and yields. For key properties there are diminishing returns with the addition of increasing amounts of fuel. These results should provide useful guidelines for the design of functional systems making use of this chemistry. <br></div>

Substituent Effects on Transient, Carbodiimide-Fueled Geometry Changes in Diphenic Acids

“…[32][33][34][35][36] The initial reaction of a single carboxylic acid group in the diacid (DA) with EDC in the presence of pyridine should generate an acylpyridinium intermediate (I) via the O-acylisourea, simultaneously forming the urea EDU as a waste product (eq 1). 22,[32][33][34] All of the substituted systems can potentially give two distinct isomers of I depending on which carbonyl reacts; for the purposes of modeling we do not distinguish these possibilities. Intermediate I can either generate the anhydride by intramolecular reaction with the other acid group (eq 2), or it can reform the starting acid by unproductive hydrolysis (eq 3).…”

“…The anhydride can hydrolyze back to the starting acid via the same acylpyridinium intermediate I (eq 2). 22,35,36…”

“…A non-parametric bootstrapping method was used to estimate the uncertainties of the regression (95% confidence interval). 22 The independence of the parameters was further confirmed by generating confidence contour plots as shown in the Supporting Information. 38 The parameters are well-constrained by the data for all seven substrates.…”

“…This is the most significant substituent effect for these diphenic acid systems; interestingly, this was not the case in our previous work on intermolecular anhydride formation in simple substituted benzoic acids, where differences in behavior could be explained mostly in terms of the parameter analogous to k 2 . 22 A close look at Figure 4 shows that changes in α level off when σ m is less than about 0.1. It is possible that this is because the anhydrides are unsymmetrical; that is, the most electrophilic carbonyl would be preferentially attacked by pyridine, and thus attack at the unsubstituted side would be favored for electron-donating substituents, leading to little difference in behavior.…”

“…1,[15][16][17] Carbodiimides, typically EDC ((N -(3-(dimethylamino)-propyl)-N -ethylcarbodiimide hydrochloride), stand out as versatile fuels. They have been used in recent reports by Boekhoven, [18][19][20] us, [21][22][23] Das, 24,25 and several other research groups [26][27][28] to generate nonequilibrium behavior. The associated chemistry is quite simple: carbodiimides react with aqueous carboxylic acids to generate carboxylic anhydrides that then undergo hydrolysis to regenerate the parent carboxylic acids.…”