Articles by: Chemjobber

The most bracing (and sad) chemical sentence you will read today

“I will roar argon into chlorine, xenon into fluorine, all the noble gases into reactive ones… My lament will terrify even the stars.” – Jessica Stern, Denial: A Memoir of Terror

From Dwight Gardner’s review in the New York Times. Dr. Stern is an expert on terrorism; she believes her interest in terror stems from a brutal and violent incident from her childhood.

By June 28, 2010 1 comment Uncategorized

Puzzling polymorphs

Polymorphism is a common and sorta crazy issue in pharmaceutical process chemistry. Basically put, a drug molecule in the solid state can have multiple crystal forms. Different impurity profiles and different crystallization techniques (solvents, heating/cooling rates) can produce different polymorphs, which can have wildly different physical properties and bioavailabilities. A famous story of troublesome polymorphism is Abbott’s ritonavir, where in the middle of manufacturing for sale (not during the R&D phase!), a new, much less soluble polymorph started showing up in batches. Moreover, once the new polymorph showed up, it was very difficult to generate the previous polymorph. Even crazier, a team of scientists went to another plant in Italy where the process was still working as desired, and soon after the team left, the new polymorph appeared. It took a crash program to understand which conditions were generating the new crystal form to get it under control.

A recent article by Pradash et al. in Organic Process Research and Development illustrates the problems of polymorphism similarly: once the authors determined that there was another crystal form (‘Form A’) than the original (‘Form B’), they undertook a screening process (looking at varieties of solvent and crystallization techniques) to find other polymorphs. Interestingly, once they discovered a new polymorph (‘Form C’), they found that it was impossible to generate Form B in their laboratories. They selected Form C for its physical properties and moved it into the pilot plant; lo, they then found Form D. This new crystal form began predominating and “those seeded crystallization processes that consistently produced Forms A and C started to produce predominately Form D in the laboratory.” (Click on image to see pictures of the polymorphs and the structure itself.)

When I read these accounts, I am filled with admiration for pharmaceutical process chemists, the interesting science that they get to do and the vast reserves of patience and sangfroid they must have.  Chemistry (and manufacturing chemistry, especially!) is based on reproducibility and consistency; when issues arise, I suspect that there is a great deal of checking and double-checking to make sure that “this is really happening to us.” Also, I can’t help but wonder if those process chemists, when these issues are discovered, wonder if the laws of the physical universe are being temporarily suspended and some Loki-like diety is having its way with them.

How’s your laundry’s chemical hygiene?

So what'd you do with those pants, anyway?

Credit: University of Ottawa EH&S

A recent report from the President’s Cancer Panel on the environmental causes of cancer* had a rather interesting recommendation relevant to chemists. As to what you could do to lower your risk and your family’s, here’s what it said (page 111):

“Family exposure to numerous occupational chemicals can be reduced by removing shoes before entering the home and washing work clothes separately from the other family laundry.”

So what do you think of that? As chemists, we are presumably more exposed than the typical person, although I suspect that there are industrial workers (coal miners?) who are even more exposed than us.

I know that I have typically avoided bringing my shoes into the home (but, then again, I’ve always taken off my shoes before I enter my home). Recently, I have begun washing my work clothes separately from my family’s. Due to my work circumstances, I’m guessing that I carry home more compound that the average chemist. Then again, it’s the same washing machine. Short of running an ethanol rinse between washes (can you imagine the cost?), I don’t know if there’s a good answer for that one.

I’m terribly interested to know what other people’s habits are about their clothing and chemical hygiene? Do you let your kids hug you when you walk in the door from work? Do you let your dog chew on your work shoes? Inquiring minds want to know…

*Folks (e.g. Derek Lowe) have been pretty critical of the report. I’ve noticed that it’s pretty long on assertion myself. Nonetheless, it’s an interesting topic.

Photo from the University of Ottawa’s lab EH&S site.

Art from molecular models

"Heme", by Alexander Kobulnicky

In my travels here and about online, I recently found the paintings of Alexander Kobulnicky. He paints molecular models of, well, molecules, ranging from the life-giving (“Heme”, to the left) to the fun-related (THC, if that’s your thing) to the life-taking (CO.) The background of the artwork is most noteworthy — Mr. Kobulnicky paints what comes to mind with each different molecule. I think that thorazine is the one with the best background, although psilocybin comes in a close second.

Each painting comes with a little description of the relevant chemistry and an interesting structural note to make a chemist’s heart warm: “These molecules are rendered as space-filling models, in a natural, low-energy conformation, and displayed from an angle that shows off as much of their structure as possible.”

While I’m not quite to the art-collecting stage of my life yet, I have to say that I’m pretty enthusiastic about owning one of these someday.

By April 28, 2010 6 comments fun, general chemistry