Water is the most studied molecule on Earth, yet a surprisingly basic question has gone unanswered for decades: when water is squeezed into gaps just a few molecules wide – as happens inside nanoscale pores, membranes, and biological channels – does it become more, or less chemically reactive?
This matters because water's most fundamental chemical property is its ability to split into two charged species, H₃O⁺ (the hydronium ion) and OH⁻ (the hydroxide ion). This reaction defines the pH, a measure of how acidic or alkaline (basic) a solution is, and underpins all of acid-base chemistry, from how enzymes work in your cells to how electrodes function in batteries. Through this research, the scientists wanted to understand whether (and how) confining water to nanometre-scale spaces affects this behaviour.
In the paper published in Science Advances , the researchers from Cambridge, Harvard, CalTech, and the Max-Planck Institute for Polymer Research found that the apparent reactivity of nanoconfined water is extraordinarily sensitive to conditions such as density, pore width, wall flexibility, and surface chemistry.
"When we compared systems under equivalent thermodynamic conditions – specifically at the same chemical potential (the quantity that determines whether a reaction proceeds), the effect of confinement largely disappeared. In other words, the confinement alone does not intrinsically change water's reactivity. This explains why experiments over the past decade have produced contradictory results," said Xavier R. Advincula, the study's lead author.
"The contradictions in the literature were largely because scientists were comparing systems at different effective pressures or densities without realising it."
To investigate the problem, researchers used machine-learning-based simulations capable of reproducing quantum-mechanical accuracy while exploring a much wider range of conditions than conventional computational approaches allow. The team studied water confined between sheets of graphene and hexagonal boron nitride (hBN), two atomically thin materials that share a similar structure but have very different surface chemistry.
Confined water droplets were also found to experience enormous internal pressures during the study. Water trapped between atomically thin sheets of graphene or hBN experiences pressures of several gigapascals – comparable to conditions found deep within the Earth – despite no external force being applied. Instead, these pressures arise naturally from van der Waals attraction between the confining layers themselves – a force that, while weak between any individual pair of atoms, becomes collectively enormous across the vast surface area of 2D materials – causing the sheets to pull together and squeeze the trapped water."
The scientists found that these extreme pressures dramatically increase water dissociation. However, when the researchers compared their results with measurements of bulk water under equivalent pressures, the confined droplets followed exactly the same trend. This showed that the enhanced reactivity was primarily a consequence of pressure rather than a unique property of confinement itself.
"What surprised us most was how much of the apparent confinement effect could be explained by thermodynamics. Once pressure and chemical potential are properly accounted for, a great deal of the complexity simply falls into place," said Prof Angelos Michaelides, of the Yusuf Hamied Department of Chemistry at the University of Cambridge.
Although confinement does not intrinsically alter water reactivity, the confining material can enhance reactivity through a specific mechanism. In nanometre-scale water droplets encapsulated within hBN, hydroxide ions (OH⁻ ) formed at the droplet edges chemically bond to the surrounding material. This interaction stabilises the ions and lowers the energetic cost of water splitting, increasing the extent of dissociation.
Importantly, this effect was absent in graphene, whose chemically inert surface does not participate in the reaction. The finding demonstrates that the confining material itself can actively influence water chemistry.
"This research provides a new framework for understanding water chemistry at the nanoscale and helps reconcile a decade of apparently conflicting studies," said Dr Christoph Schran, of the Theory of Condensed Matter Group at the Cavendish Laboratory.
"More importantly, the work offers a practical design principle for engineering nanoscale chemical environments. Rather than focusing solely on the size of pores or channels, we can tailor water reactivity by choosing a confining material whose surfaces interact with the products of water dissociation and by controlling the pressures generated within confined spaces."
The research could prove particularly valuable for technologies that rely on confined water, including hydrogen fuel cells, batteries, ion-selective membranes and catalytic systems.
The researchers now plan to investigate more realistic confinement environments, including materials containing defects and edges, which are common in practical devices. They also hope to connect their predictions with experimental measurements using advanced spectroscopic and nanofluidic techniques.
In parallel, the researchers are exploring ways to screen large families of two-dimensional materials and surface chemistries to identify candidates capable of enhancing or suppressing water reactivity for specific technological applications.
