Diels–Alder Reactions in Water Are Determined by Microsolvation

Abstract

Nanoconfined aqueous environments and the recent advent of accelerated chemistry in microdroplets are increasingly being investigated for catalysis. The mechanisms underlying the enhanced reactivity in alternate solvent environments, and whether the enhanced reactivity due to nanoconfinement is a universal phenomenon, are not fully understood. Here, we use ab initio molecular dynamics simulations to characterize the free energy of a retro-Diels-Alder reaction in bulk water at very different densities and in water nanoconfined by parallel graphene sheets. We find that the broadly different global solvation environments accelerate the reactions to a similar degree with respect to the gas phase reaction, with activation free energies that do not differ by more than kbT from each other.The reason for the same acceleration factor in the extremely different solvation environments is that it is the microsolvation of the dienophile's carbonyl group that governs the transition state stabilization and mechanism, which is not significantly disrupted by either the lower density in bulk water or the strong nanoconfinement conditions used here. Our results also suggest that significant acceleration of Diels Alder reactions in microdroplets or on-water conditions can't arise from local microsolvation when water is present, but instead must come from highly altered reaction environments that drastically change the reaction mechanisms.

A critical analysis of electrospray techniques for the determination of accelerated rates and mechanisms of chemical reactions in droplets

“…In addition to experiments, modelling the kinetics of reactions within droplets and at interfaces can help clarify our understanding of the mechanisms leading to reaction acceleration in micro-and nano-compartments. A few recent examples of such contributions include the kinetic modelling of reactions in microemulsions, 60 molecular dynamics simulations of a cycloaddition reaction at the water-graphene interface, 110 quantum mechanical calculations of the energies of desolvated molecules at the water-vacuum interface 61 and estimation of the magnitude of electric elds in microdroplets. 73 Finally, there is an important distinction between two different objectives that one might have when studying the acceleration of reaction rates in aerosolized nano-and microdroplets.…”

A kinetic description of how interfaces accelerate reactions in micro-compartments

“…These rate coefficients will be sensitive to the molecular structure of the reactants, intermediates and products as well as additional compartment features such as solvent, electric elds and pH gradients that can alter reaction energetics and transition states at the interface. 23,52,53 Rate coefficients for adsorption and desorption, which also control surface reaction rates via interfacial concentration, will be similarly sensitive to the exact nature of the interface (i.e. liquid/vapor vs. oil/aqueous) as well as the solvent environment of the compartment.…”

“…There are many examples where nano-connement 20 of a small number of molecules or atoms has a profound inuence on physical and chemical properties; including the electronic structure of quantum dots and the transport and reactivity in carbon nanotubes, 21 zeolites, nanovessels, 22 metal organic frameworks, cells, etc. For these cases, compartmentalization produces properties and behavior not observed in their macroscopic analogs or described by continuum theories because connement is on the order of molecular/atomic dimensions, solvent correlation lengths 23,24 and/or is governed by stochastic uctuations of small numbers of molecules. [25][26][27][28][29] In contrast, it is not immediately obvious why connement of many, many millions of solute molecules in a micron-sized droplet or emulsion would produce behavior substantially different from what is observed in a beaker.…”

An isolated water droplet in the aqueous solution of a supramolecular tetrahedral cage

“…In both natural and artificial nanometer-sized environments, confined water displays uniquely modified structure and dynamics with respect to the bulk liquid (15)(16)(17)(18). Recently, these modified properties were also found to have significant implications for the mechanism and energetics of reactions taking place in confined water with respect to those observed in bulk aqueous solution (19)(20)(21). In a pioneering study on supramolecular assemblies, Cram and collaborators (22) concluded that the interior of those cages is a "new and unique phase of matter" for the incarcerated guests.…”