On Jargon

While reading Gary Stix's interview with Breaking Bad scientific advisor Prof. Donna Nelson, I stumbled upon a very telling chunk of text (emphasis mine):

"...the reduction step [for methamphetamine production] can vary from one synthesis to another, and there's a lot of differences in the reducing agents. And so I said, I don't know what reagent you want. They said to send them a list, and they liked the one that was aluminum-mercury because it would be easier for the actors to say those words.

That's another example of where I let [the producers] be boss. I wouldn't go back to them and suggest another reagent because it might be safer, cheaper, or have a higher yield. I just said, 'yes, sir.'"

"Sodium cyanoborohydride? No way am I saying that!"
Credit: AMC

Food for thought, especially for those of us trying to package chemistry in a more palatable format for folks outside the lab. But, the more I scratched my head over this situation, the more I wondered...are reducing agents that tough to pronounce?

Over at xkcd, Randall Munroe cheekily trounced our current cultural fixation on trochees, spoken words with a two-syllable stressed / unstressed pattern (ninja, pizza, Wal-Mart, Ke$ha, Xbox, etc.). "Aluminum-mercury," though taken right from the periodic table, hardly rolls off the tongue: seven* syllables!

"Classic" reagents for the reaction in question, like sodium cyanoborohydride (10 syllables) or sodium tris-acetoxyborohydride (12) certainly won't get by the writers without a grumble. But what about formic acid (4, with two trochees)? Raney nickel (4, two trochees) should also pass muster. Even better, maybe you could just fold the first two reductants into the generic "borane" (2, trochee) category?

Hey, AMC: Let's do lunch.

*And, of course, 8 if you live in the UK, and add that extra "i" to aluminium!

The Simpsons: Just Like "Cooking"

Ever have that feeling like you somehow missed the boat? 

Back in 2011, TV sitcom stalwart The Simpsons aired Episode #491 (NABF20), entitled "The Food Wife." I caught it in reruns for the first time tonight. Aside from the hilarious send-ups of celebrity chefs and uptown foodies, the episode turned a truly dark corner when it compared molecular gastronomy to...cooking methamphetamine. 

Really, it's true - Gothamist and Esquire both scribed pieces about the show last year.

Credit: Simpsons Wikia | 20th Century Fox

Breaking Bad gives its swan song later this year. We know Walter and Jesse's lab work has truly permeated pop culture when references pop up on prime time comedy cartoon shows.

And how often do you get to see Homer Simpson stumble around a garage lab*? Priceless.

*(Even one that doesn't make any practical sense; are those goofy cones supposed to be filters? And why do TV writers always think we connect reflux retorts with 'mad scientist'-esque glass tubing?)

Illegal Drugs Spur Chemists to Create Cures

White powders marketed on grocery shelves as “bath salts” are quickly becoming problematic for politicians and police, as reported in the July 17^th New York Times.  These “salts,” derivatives of a compound called methylenedioxypyrovalerone (MDPV) cause many of the same symptoms as methamphetamine intoxication. The wide availability of these new mixtures, compounded by their ease of synthesis and seemingly no lack of supply, has led to an explosion in their abuse (Note: I won’t cover the chemistry behind MDPV, the active ingredient, because my in silico mentor David Kroll’s posts on Terra Sigilata have mostly covered it).

That’s the gist of the article, in which illicit chemical synthesis fuels a new drug craze, and the public perception of chemists is dragged down again by sound bites such as “state bans thwarted by chemists who have to change only one molecule… to make [the salts] legal.” What happened to fair and balanced coverage?

For every illegal manufacturer of psychoactive compounds hoping for addiction to promote sales, there are many more chemists working on analogs of bioactive substances to treat disease.  Compounds that show high potential for abuse tend to interact with three neurotransmitters: serotonin, dopamine, and norepinephrine. In the case of bath salts, the main ingredient is a norepinephrine-dopamine reuptake inhibitor (NDRI), which allows these neurotransmitters to stay longer in the synapse, creating feelings of pleasure and wakefulness. Phenethylamines, such as MDPV, meth, or Ecstasy, the popular club drug, are one major class of compounds which activates these receptors, and are easily tweaked synthetically to prepare drug leads for Parkinson’s disease, schizophrenia, and ADHD.

Prof. David E. Nichols, of Purdue University, has devoted much of his career to understanding the mechanisms by which addictive drugs can interact with brain receptors, and designing novel compounds to take advantage of these traits (See this October 30, 2010 Wall Street Journal piece for Nichols’ comments regarding black market applications of his academic work). Prof. Nichols has synthesized variants of psilocybin, mescaline, and notably for this particular story, MMAI, a “cyclized” version of a typical methamphetamine scaffold.  On the day the NYT article went to press, Prof. Nichols had a J. Med. Chem. ASAP publication (DOI: 10.1021/jm200334c) appear online, in which his group prepared four new methylated analogs of their lead compound dihydrexidine. This analog, developed off the phenethylamine scaffold, has been shown to bind to the D₁ dopamine receptor, and both improve blood flow to the brain and to reverse Parkinson's-like symptoms.



Photo Credit: obrag.org

 Two other medicinal chemists are using methamphetamine derivatives as “Trojan horses” to trick the body into immunizing itself against the drugs. Their end goal is a vaccine that could be administered to control meth addiction. Kim Janda, of the Scripps Research Institute, and F. Ivy Carroll of the Research Triangle Institute (just down the block from David Kroll!) have both recently reported their groups’ respective efforts towards methamphetamine vaccines. Each group strategically introduces a hapten, an immunological “stamp” that latches onto a human protein, which the body can use to recruit white blood cells to the foreign substance.

Janda (JACS 2011, 6587) attaches a six-carbon chain ending in a thiol (SH) group to the amino group of (+)-methamphetamine, the more potent enantiomer, and observes high antibody titres in mouse models. Carroll (J Med Chem, 2011, ASAP) also uses a sulfur antigen, but attaches his via an amide linker connected to the aromatic core. After connecting this linker to a suitable immune-responsive protein, Carroll generates a monoclonal antibody with a 6.8 nm K_D for (+)-meth.

Update (July 30, 6:50PM) - Changed "bloodstream" to "synapse," since commenter gippgig is (again) correct that the compounds influence synaptic function, not bloodstream chemistry. Thanks!