Statistical Thermodynamics Unveils How Ions Influence an Aqueous Diels‐Alder Reaction

Abstract

The kinetics of Diels‐Alder (DA) reactions in water has been known to be altered by salts for a long time. Yet the question how salts influence the reaction rate, either as rate‐enhancing or rate‐reducing additives, has so far remained unresolved. Conflicting hypotheses involve (i) indirect salt contributions through the modulation of internal pressure and (ii) making (or breaking) of the so‐called “water‐structure” by salts that strengthen (or weaken) the hydrophobic effect. In contrast to the qualitative nature of these hypotheses, here we answer this question quantitatively through a combination of transition state theory and fluctuation adsorption‐solvation theory (FAST) using the DA reaction between anthracene‐9‐carbinol and N‐ethylmaleimide as an example. We show that rate enhancement is driven by the salting out of the hydrophobic reactant, while rate‐enhancing salts exhibit stronger affinity to the transition state.

Diels–Alder Cycloaddition Reactions in Sustainable Media

“…They also concluded that ammonium salts bearing long alkyl groups promote the dissolution of the nonpolar reactants by rearranging water molecules up to a second solvation shell around the dissolved salts, thus behaving as anti-hydrophobic or salting-in agents. In another study, Shimizu and coworkers investigated the effect of several rate-enhancing salts (e.g., LiCl, guanidinium sulfate) and rate-reducing salts (e.g., NaClO 4 , guanidinium acetate) for the same reaction, demonstrating that the interactions between ions and diene 54 are crucial for controlling the reaction rate [94]. A rate reduction was observed for the reaction in the presence of rate-reducing salts, which show a preferential interaction with diene, and is consistent with the increased 54 solubility.…”

Mechanism of dye solubilization and de-aggregation by urea

“…Note that the same 𝑉 𝐸 was used in Eq. ( 2) for calculating 𝐺 𝑢1 ′ and 𝐺 𝑢2 ′ [59,61]. By doing so, the solvation shell relationships, Eqs.…”

“…for example, a cosolvent larger in molecular size than water has a negative contribution to 𝐺 𝑢2 ′ from the excluded volume effect [59,61].…”

Response to the “Comments on ‘Statistical thermodynamics of casein aggregation: Effects of salts and water’ [Biophys Chem. 247 (2019) 34–42]”

“…However, kinetics and thermodynamics of aggregation, as stated in Section 2.3, are different [8,13,18,19]. Different phenomena require different theoretical approaches, and yield different results [8,13,18,19].…”