Solvent miscibility and polarity chart

Choosing a solvent comes down to a few questions. Will it mix with water? How polar is it? How easily does it evaporate? Can a UV detector see through it? This chart answers those questions for 15 common laboratory solvents, with a source for every value, and explains how to read it.

For choosing a solvent for a particular peptide, see peptide solubility. For the solvents used in HPLC, see HPLC and LC-MS solvents. Terms are defined in the glossary.

The chart

Solvents are listed from most polar to least polar.

Sources:

• Water mixing and boiling points: PubChem, linked from each solvent name. Water solubilities are at 25 °C, and boiling points are at normal atmospheric pressure, given to the nearest degree.
• Polarity index and UV cut-off: the Burdick & Jackson polarity index and UV cut-off tables. Ethanol isn't on their polarity index list, so it is left blank rather than filled from a different scale. The UV cut-offs for hexane and THF are for those suppliers' UV grades.

How to read the chart

What does miscible mean?

Two liquids are miscible if they mix in any proportion to form a single layer; immiscible liquids, such as oil and water, separate into two layers.

Mixes with water?

"Yes" means the solvent is miscible with water: it mixes in any proportion to give one clear layer. "Partly" and "barely" mean only a limited amount dissolves, shown in grams per litre. Above that, you get two layers.

Solvents that don't mix with water are useful for exactly that reason. In an extraction, a compound moves from the water layer into a solvent such as ethyl acetate or dichloromethane, and the two layers are then separated.

Polarity index

The polarity index ranks how strongly a solvent interacts with polar compounds. Higher means more polar. It's a practical guide to what a solvent will dissolve, and to how strong it is as an eluent in chromatography. It isn't a fundamental property like boiling point, and other polarity scales rank a few solvents differently. That is why the chart sticks to one scale.

Boiling point

The boiling point tells you how easily a solvent evaporates. Low-boiling solvents such as diethyl ether, dichloromethane and acetone evaporate quickly. They are easy to remove, but they also build up vapour fast, so they are handled in a fume cupboard. High-boiling solvents such as DMSO and DMF are hard to remove by evaporation. They also don't come out during freeze-drying, as the solubility guide notes.

DMSO has another quirk: it freezes at about 18.5 °C, so a bottle can turn solid in a cool lab (PubChem). Warming it gently returns it to a liquid.

UV cut-off

Below its UV cut-off, a solvent absorbs too much ultraviolet light for a UV detector to see through it. Peptides are detected at about 210–220 nm, so HPLC needs solvents with cut-offs well below that. Acetonitrile and water, at 190 nm, are the usual pair. Acetone, at 330 nm, is useless for low-wavelength UV work. See light and the electromagnetic spectrum.

Like dissolves like

The rule of thumb behind the chart is "like dissolves like". Polar solvents dissolve polar and charged compounds, and non-polar solvents dissolve non-polar ones. Water, at the top of the chart, dissolves salts and sugars. Hexane, at the bottom, dissolves oils and waxes. See solvents, solutes and solutions for what a solvent is.

Peptides sit in between. Charged and polar side chains favour water and the polar solvents near the top of the chart. Long stretches of hydrophobic residues favour less polar solvents. That is why a hydrophobic peptide is often started in a small amount of DMSO or acetonitrile before water is added. For the reasons behind polarity, see chemical bonds and polarity.

Mixing solvents with each other

Most of the polar solvents in the chart mix freely with one another, and with water. The exceptions are mainly the very non-polar hydrocarbons. The grid below shows every pair.

Of the 105 pairs in the grid, 11 form two layers (Burdick & Jackson miscibility table):

• Water with ethyl acetate, chloroform, dichloromethane, diethyl ether, toluene and hexane.
• Hexane with DMSO, DMF, acetonitrile and methanol.
• DMSO with diethyl ether.

"Immiscible" in the table means the pair doesn't mix in all proportions; a little of one can still dissolve in the other, as the water-solubility column above shows. Acetonitrile, for example, mixes with methanol, ethyl acetate and chloroform, but not with many saturated hydrocarbons such as those in petroleum fractions (PubChem). For any pair not covered here, check a full miscibility table or the solvents' data sheets before mixing.

Mixing some solvents with water also changes the volume and temperature. Acetonitrile cools as it mixes with water, and methanol warms. See HPLC and LC-MS solvents.

Safety

Every solvent in this chart has hazards, and several are highly flammable and carry the flame hazard symbol. Solvents also pass through glove materials at different rates, so check a glove maker's breakthrough chart; see lab gloves. Each one has its own safety data sheet, which sets out how to store, handle and dispose of it. Read it before use. See COSHH and safety data sheets, and for storage, storing lab chemicals safely.

Related guides

For how solvents are used to separate compounds, see how chromatography works, and for how solvent polarity moves spots on a TLC plate, see Rf values and thin layer chromatography. For water itself, see lab water. Every lot has its own COA, published on the product page and on that lot's own page. See Quality.