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DMSO biochemistry

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the bumbling biochemist

DMSO, DiMethyl SulfOxide, is a common goto solvent and cryoprotectant.

blog form: https://bit.ly/dmso_biochemistry

DMSO can serve as a good carrier for getting compounds into cells or aqueous(waterbased) reaction mixtures because it can dissolve "most" things but can also hang out with (is miscible in) water and many organic (hydrocarbonbased) solvents. Why?

DMSO is highly polar (jargonwise, we can say it as a high dielectric constant). This means it has regions of positive & negative charge/partial charge, which allows it to form charge (&/or partialcharge)based interactions with polar parts of molecules (solutes & water).

But it also has has nonpolar regions (its methyl groups) which are good for dissolving “organic” (hydrocarbonbased) compounds, such as those developed in ochem labs. The methyl groups allow it to form hydrophobic interactions with nonpolar parts of molecules, so can help compounds that are "too nonpolar" to dissolve in pure water dissolve in a waterbased solution.

It’s also aprotic it doesn't have an easilydonated proton. This can have various consequences, including affecting ochemy reaction rates and pathways (think SN1 vs SN2 if that means anything to you!). It can't stabilize anions as well as a protic solvent could. More on these “solvent effects” here: http://bit.ly/nucleophilefiles ; YouTube:    • Nucleophiles, electrophiles, & “bases...  

DMSO’s oxygen can serve as an Hbond acceptor, but it doesn't have Hbond donors, so it can integrate itself into water networks, but weakens them (can't form as strong of networks), allowing it to serve as a cryoprotective agent (CPA) (cryoprotectant). Much more on that here: https://bit.ly/cryopreserving_cells YouTube:    • Cryopreserving cell stocks    

a few more things to know about DMSO…

Because it can dissolve so many things, it's often used as a goto solvent for highthroughput (think robots) pharmacological compound screening experiments. The more "organic" (often used to refer to hydrophobicity) a compound is, the higher the % of DMSO you'll need, but you typically want to keep the %DMSO as low as possible because it can affect various reactions, etc.

Crucial: Always include a DMSOonly ("carrier") negative control (with same DMSO % as your test conditions) to see if DMSO is causing any effects that aren't specific to what you're trying to see is causing effects!

Proteins are typically used to a watery environment. Too much DMSO can therefore disrupt protein interactions & cause proteins to "crash out" (precipitate) if the %DMSO gets too high and the proteins denature (unfold).

DMSO can cross cell barriers and therefore can be used to carry compounds into cells (in dishes in the lab or transdermally in medicine (e.g. through patches)) so be careful working with it!

Common concentrations…

Typically, for cell culture work you want to keep %DMSO ≤ 0.1% (preferable below 0.05%) when delivering drug compounds into cells.

And remember your control(s)!

For invitro experiments with proteinbased solutions, depending on the protein & the experiment you might be able to go up to ~5%, but you might need to test a range of concentrations to see what works.

A 10% DMSO/media solution is often used to cryopreserve cell stocks.

Beware changing concentrations!

DMSO is hygroscopic it can draw in water from the air, lowering the %DMSO of a solution.

DMSO has a higher freezing point than water, so freeze/thaw cycles can also mess with solubility, etc.

Initial compounds coming out of pharmacological chemistry labs often need a lot of DMSO because the reactions that the chemists do to make the molecules typically require “organic”, nonaqueous, conditions. One of the biggest hurdles with taking an initial hit from a compound screen and turning it into an actual usual drug is getting it so the compound doesn’t need the DMSO!

So, there you go, that’s why DMSO is both friend and foe!

Some sources and resources in the comments

posted by Zavrhkomxm