I took the day off yesterday, but this morning it's back to the lab. I didn't leave any chemistry going in my hood, so there should be no surprises there, unless one of the things I've left sitting around took the opportunity to crystallize.

Just about every drug candidate we make should have one or more crystalline forms - we don't usually bother testing molecules that are too small to be solids at room temperature. But that doesn't mean that they all crystallize easily. Some things really need coaxing. If there's the least bit of water or solvent left in them, they sit around as thick oils, gums, or syrups.

Some of them will decide, after a few weeks, to finally start growing some crystals. Perhaps some of the volatile impurities finally evaporate, or possibly the molecules just finally banged into each other the right way and decided to set up housekeeping in the solid state. And you can't rule out the beneficial effects of lab dust for starting things off, either. There are all kinds of legends about labs in the old days that cleaned things up so well that their stock-in-trade compounds wouldn't crystallize any more.

I had a compound from my first year of graduate school, a light yellow syrup that I kept around my whole time there, that finally decided to start growing thick faceted crystalline plates in my (and its) fourth year. This just might have had something to do with most the compounds I made being carbohydrate derivatives, which have a fairly accurate reputation for not crystallized except at gunpoint.

The thicker the syrup, the slower these things happen, as you'd figure. Real crystallizations out of solution, by contrast, can be pretty dramatic - a sudden whoomphing snowstorm in the flask. Do it too fast, though, and impurities will be entrained and come down with your solid. The ideal is a noticable, steady growth, the sort of thing you leave overnight and come back for.

For the most part, we don't care too much during the synthesis if things are solids or not. It makes compounds easier to transfer and handle if they are, but you can always dissolve up a goo or sludge in some solvent. But for final drug candidates, a reproducible crystalline form is a good thing to have. It's close to crucil if you dose as a suspension. You'll get into trouble if you keep dosing poorly characterized solids, which might contain various amounts of various crystal forms along with amorphous material, all of which dissolve at different rates.