For those who were wondering, my copper reactions the other day worked out just fine. They started out a beautiful blue (copper iodide and an amino acid in straight DMSO – if that’s not blue it’s maybe going to be green, and if it’s not either one you’ve done something wrong). Of course, the color doesn’t stay. The copper ends up as part of a purple-brown sludge that has to be filtered out of the mix, which is the main downside of those Ullman reactions, no matter how people try to scrub them up for polite company.
And DMSO is the other downside, because you have to wash that stuff out with a lot of water. That’s one of the lab solvents that everyone has heard of, even if they slept through high school chemistry. But it’s not one that we use for reactions very much, because it’s something of a pain. It dissolves most everything, which is a good quality, but along with that one comes the ability to contaminate most everything. If your product is pretty greasy and nonpolar, you can partition the reaction between water and some more organic solvent (ether’s what I used this time), and wash it around a lot. But if your product is really polar, you could be in for a long afternoon.
That mighty solvation is something you need to look out for if you spill the stuff on yourself, of course. DMSO is famous for skin penetration (no, I have no idea if it does anything for arthritis). And while many of my compounds are not very physiologically active, I’d rather not dose myself with them to check those numbers. At the extreme end of the scale, a solution of cyanide in DMSO is potentially very dangerous stuff indeed. I’ve done cyanide reactions like that, many times, but always while paying attention to the task at hand.
Where DMSO really gets used is in the compound repository. That dissolves-everything property is handy when you have a few hundred thousand compounds to handle. The standard method for some years has been to keep compounds in the freezer in some defined concentration in DMSO – the solvent freezes easily,
down around where water does (Not so! Actually, I've seen in freeze in a chilly lab a couple of times, now that I'm reminded of that in the comments to this post. Pure DMSO solidifies around 17 to 19 C, which is about 64 F C - a bit lower with those screening compounds dissolved in it, though).
But there are problems. For one thing, DMSO isn’t inert. That’s another reason it doesn’t get as much use as a lab solvent; there are many reaction conditions during which it wouldn’t be able to resist joining the party. You can oxidize things by leaving them in DMSO open to air, which isn’t what you want to do to the compound screening collection, so the folks there do as much handling under nitrogen as they can. Compounds sitting carelessly in DMSO tend to turn yellow, which is on the way to red, which is on the way to brown, and there are no pure brown wonder drugs.
Another difficulty is that love for water. Open DMSO containers will pull water in right out of the air, and a few careless freeze/thaw cycles with a screening plate will not only blow your carefully worked out concentrations, it may well also start crashing your compounds out of solution. The less polar ones will start decided that pure DMSO is one thing, but 50/50 DMSO/water is quite another. So not only do you want to work under nitrogen, if you can, but dry nitrogen, and you want to make sure that those plates are sealed up well while they’re in the freezer. (As an alternative, you can go ahead and put water in from the start, taking the consequences). All of these concerns begin to wear down the advantages of DMSO as a universal solvent, but not quite enough to keep people from using it.
And what about the compounds that don’t dissolve in the stuff? Well, it’s a pretty safe bet that a small molecule that can’t go into DMSO is going to have a mighty hard time becoming a drug, and it’s a very unattractive lead to start from, too. That’s the sort of molecule that would tend to just go right through the digestive tract without even noticing that there are things trying to get it into solution. And as for something given i.v., well, if you can’t get it to go into straight DMSO, what are the chances you’re going to get it into some kind of saline injection solution? Or the chances that it won’t crash out in the vein for an instant embolism? No, the zone of non-DMSO-soluble small organics is not a good place to hunt. We’ll leave proteins out of it, but if anyone knows of a small molecule drug that can’t go into DMSO, I’d like to hear about it. Taxol, maybe?