Two Solids Make a Liquid. Why Deep Eutectic Solvents Are Still Waiting

Two white solids go into a beaker. One melts at 302 °C, the other at 133 °C. Warm them together to 80 °C, stir, let the result cool, and what is left at room temperature is a clear, syrupy liquid that will not freeze until 12 °C. That trick is twenty-three years old, it has produced thousands of papers, and on 5 October 2026 C&EN ran a CAS patent analysis under a headline that sums up where it stands: “Deep eutectic solvents are still waiting in the wings.”

The interesting part, for anyone who buys the raw materials, is not the hype or the wait. It is the list of ingredients. The most-studied deep eutectic solvents are built from urea, glycerol, ethylene glycol, citric acid, oxalic acid and propylene glycol, which are bulk industrial chemicals rather than exotic reagents. And the most common reason a DES recipe fails to reproduce has nothing to do with exotic chemistry. It is water.

This is a chemistry explainer built on published research. It makes no claim that any solvent, deep eutectic or conventional, is safer or better for the environment than another, and it is not a formulation recommendation for any process.

What did C&EN report this week?

C&EN reported on 5 October 2026 that deep eutectic solvents are growing fast on paper and slowly in plants: a CAS analysis of more than 20,000 publications finds 83 percent are journal articles, and the solvents still have few industrial applications. The piece, by C&EN executive business editor Michael McCoy for the magazine’s Eye on Patents series with CAS, compares DESs with ionic liquids: both are liquids “despite properties that would suggest otherwise,” and both “arguably also suffer from hype by enthusiastic researchers.” Ionic liquids have at least one industrial success, as an alkylation catalyst in a Chevron refinery. Deep eutectic solvents, McCoy writes, “can’t claim many real-world applications.”

Two organisations in the article are trying to change that. Bioeutectics, founded in Argentina in 2020 and now based in Tulsa, Oklahoma, raised $2.1 million in 2024 in a round led by the specialty chemical maker Syensqo, and has evaluated eutectic systems with personal-care and cosmetic companies as alternatives to glycols, silicones and ethanol. Southwest Research Institute in San Antonio is testing DESs for reactive carbon capture, in which carbon dioxide is absorbed into the solvent and reduced at a cathode to carbon monoxide or formate without a separate compression step.

Silva lists what that validation means: reproducibility, long-term stability, and toxicological and regulatory acceptability. SwRI scientist Miles Salas names the commercial barrier more bluntly: “A major factor is definitely cost.” Another is habit: “you also have to fight against decades and decades of traditional solvent use.”

How do two solids make a liquid?

Two solids make a liquid because the donor’s hydrogen bonds to the chloride ion stop choline chloride from rebuilding its crystal lattice, so the mixture melts far below either component. In choline chloride the chloride ion is a strong hydrogen-bond acceptor. Urea, glycerol, ethylene glycol and carboxylic acids all carry N–H or O–H groups that donate hydrogen bonds. Mixed in the right ratio, the donor molecules cluster around the chloride, the tidy ionic lattice of the salt can no longer form, and the melting point of the mixture collapses.

The paper that named the effect is two pages long. Andrew Abbott’s group at the University of Leicester published it in Chemical Communications in 2003, and its central sentence still carries the field:

The eutectic falls at a urea-to-choline-chloride mole ratio of 2. By mass that is 120.1 grams of urea for every 139.6 grams of choline chloride, so urea is about 46 percent of the liquid. The method section is one line: the components were heated to 80 °C and stirred “until a homogeneous liquid was formed.” No reaction, no by-product, no purification. That ease, as Silva notes, is exactly why there are so many papers.

Which pairs does everyone study?

Most published deep eutectic solvents pair choline chloride with a commodity hydrogen-bond donor. CAS counted patents and journal articles for every pair in its collection from 1931 to February 2026, and C&EN published the top 20. The leaders, with the partner Alliance Chemical lists marked:

Reline, ethaline and glyceline are the three most-studied deep eutectic solvents. Reline is choline chloride and urea in a 1:2 mole ratio and freezes at 12 °C; ethaline is choline chloride and ethylene glycol, 1:2; glyceline is choline chloride and glycerol, 1:2. Together they account for 8,017 of the patents and articles CAS counted for its top 20 pairs.

Two things stand out. First, the acceptor side is narrow: choline chloride appears in most of the top 20, and the fastest-growing family, per CAS, pairs betaine with glycerol, urea, lactic acid or ethylene glycol, with betaine–ethylene glycol publications growing about 53 percent a year from 2021 to 2025. Alliance Chemical does not list choline chloride or betaine. Second, the donor side is the commodity side. Urea, glycerin and the glycols are bought by the tonne for fertilizer, personal care and heat transfer, which is why the cost argument for DESs is mostly an argument about the acceptor and about processing, not about the donor.

Why hasn’t industry adopted them?

Because a solvent has to behave the same way every time, at scale, and DESs are hard to pin down. CAS’s own July 2026 analysis, written by Jeremy Krogman and Hina Goyal, says the field “remains predominantly in the fundamental research phase with limited translation to commercial applications.” It names two physical problems before any commercial one:

Viscosity and water are linked. Adding a little water is the cheapest way to thin a DES, and it is also the fastest way to stop it being one.

How much water can a deep eutectic solvent take?

A choline chloride–urea DES keeps its structure up to about 42 wt% water and becomes an ordinary aqueous solution at about 51 wt%, and that limit is easy to reach once every source of water is counted. DESs are made of ions and hydrogen-bonding molecules, so they pull water out of the air. A University of Bath team led by Karen Edler used neutron scattering at the ISIS facility to watch what that water does to choline chloride–urea, and opened their 2017 paper in Angewandte Chemie with a warning:

Their result is generous at first: the DES nanostructure survives to about 42 wt% water, because the water is tucked into domains around the choline cations. At 51 wt% (83 mol%) that arrangement breaks, and the authors write that the mixture “is best described as an aqueous solution of DES components.” They also stress that the structure is “significantly altered, even at low hydration levels,” which is why they ask every paper to report its water content. Abbott’s 2003 samples were measured at less than 1 wt% water, from amides of more than 99 percent purity that were “dried under vacuum prior to use.”

Here is where a purchase order can quietly ruin an experiment. Water arrives in three ways before anyone opens a tap: as the solvent of a diluted product, as water of crystallisation in a hydrate, and as moisture picked up in storage. Take glyceline, one mole of choline chloride (139.62 g) to two of glycerol (184.19 g), and supply the glycerol from a solution instead of neat glycerin:

Hydrates do the same thing more politely. Citric acid monohydrate is 8.6 percent water by mass; oxalic acid dihydrate, the common form of oxalic acid, is 28.6 percent water. Some published recipes call for the hydrate on purpose, and plenty call for the anhydrous form. A substitution that looks trivial on a requisition is a different solvent in the beaker.

What this means on a specification

If you are formulating, scaling up or simply trying to reproduce a paper, the donor is the part you are most likely to buy from a chemical distributor, and these are the questions that move the result:

And then store the finished solvent like the desiccant it is: closed, dry, with its water content measured, typically by Karl Fischer titration, and recorded with the batch. That one number is the difference between a result someone else can reproduce and one they cannot.

A word on what this article does not say. It describes what C&EN and CAS reported, what the founding and structural papers measured, and what water does by the arithmetic. It does not say any DES is ready for a particular process, it does not say any of these chemicals has been validated by us for DES use, and it makes no claim about ours beyond what is printed on the product listing and the certificate.