The Intrinsic Role of Nanoconfinement in Chemical Equilibrium: Evidence from DNA Hybridization

Abstract

Recently we predicted that when a reaction involving a small number of molecules occurs in a nanometric-scale domain entirely segregated from the surrounding media, the nanoconfinement can shift the position of equilibrium toward products via reactant-product reduced mixing. In this Letter, we demonstrate how most-recently reported single-molecule fluorescence measurements of partial hybridization of ssDNA confined within nanofabricated chambers provide the first experimental confirmation of this entropic nanoconfinement effect. Thus, focusing separately on each occupancy-specific equilibrium constant, quantitatively reveals extra stabilization of the product upon decreasing the chamber occupancy or size. Namely, the DNA hybridization under nanoconfined conditions is significantly favored over the identical reaction occurring in bulk media with the same reactant concentrations. This effect, now directly verified for DNA, can be relevant to actual biological processes, as well as to diverse reactions occurring within molecular capsules, nanotubes, and other functional nanospaces.

Confinement effects on DNA hybridization in electrokinetic micro‐ and nanofluidic systems

“…In the past, molecular dynamics simulations have suggested that confinement favors the bound state of short DNA oligomers because it increases the relative free energy of denatured oligomers, while simultaneously decreasing the free energy barrier of renaturation . Other forces, such as reduced entropy of mixing, may impact DNA affinity kinetics, resulting in a decrease in k off with confinement .…”

“…Rubonovich et al. performed further analysis on the experiments of Shon et al., and suggested the results represent a nanoconfinement entropic effect on chemical equilibrium ‐ stabilizing the reaction products and reducing k off . In addition, Galvin et al.…”

The Nature and Catalytic Function of Cation Sites in Zeolites: a Computational Perspective

“…In addition to the synergistic effects arising from the cooperation between the sites of different chemical nature discussed in the previous sections, the presence of multiple sites of the same nature inside the molecular‐sized zeolite pores can be crucial for the reactivity and catalytic properties of zeolites. The high density of the active sites in a confined space allows forming multiple interactions with the reactant molecules that define their specific orientation in space, which, in turn, may facilitate and direct their transformations along the predefined paths . This closely resembles the molecular recognition mechanism used by many enzymes and supramolecular catalysts to selectively activate substrates.…”

Chemistry in nanoconfined water

“…For instance, theoretical works based on statistical arguments 13,14 have coined the term “nanoconfinement entropic effects” to describe the way in which chemical equilibrium is affected when considering only a small amount of molecules, observing a considerable shift w.r.t. the equilibrium in the macroscopic limit originating in the reduction in number of reactant–product mixed microstates.…”