Friday, September 23, 2011

In Which You are What You Eat

I love food. Always have – both the process of making food (which may be why I’m a synthetic chemist) and the joy of consuming one’s labors (which lab work definitely doesn’t allow!). Recently, however, modern science blurs the line between the stomach and brain. “You are what you eat” no longer just refers to body weight or proper nutrient intake. We humans are superorganisms, meaning that our intestinal microbiology plays a huge role in our everyday lives. Turns out, where you were born, where you live, what you eat, and where you’ve travelled can all influence the metabolic phenotype (appearance) of the bacteria that inhabit your intestinal tract.
Hey baby, what's your gut microbiome?
Credit: Healthy Perceptions blog
Some microbiologists posit that humans can be grouped, not by race, creed, height, or sex, but by “gut profile.”  A recent multi-institution Nature paper, led by Bork and Ehrlich, disclosed three major enterotypes (gut profiles), based on DNA sequencing (of, well, poop) of 22 people from 4 different countries. The scientists try not to paint too broad a picture with this initial result, but note that gut bacteria influence key genes that regulate aging and body mass index, which may suggest microbial management of a wide variety of diseases.
Your gut bacteria also impact your emotions. WSJ’s Jonah Lehrer reports that yogurt – specifically the kind filled with “good” (probiotic) bacteria – can actually cause marked behavioral effects, at least in mice. Probiotic-fed mice showed fewer symptoms of stress and anxiety, even when placed in new situations. An ideal cure for modern social anxiety, right? Unfortunately, no: other scientists interviewed quickly point out neurological patients’ inability to feel fear or stress causes them to make even worse future decisions in similar situations, since they lack the negative feedback from the prior event.
Mmm, gene regulation!
Yogurt aside, your salad may also be helping to regulate your genes. Earlier this week, researchers in China disclosed new methods that can detect short strands of plant-derived RNA present in human bodily fluids. The researchers were especially surprised to find certain microRNAs actually inhibited the removal of LDL (low-density lipoprotein, the so-called “bad cholesterol”) from the bloodstream. Overall, the team found about 40 different microRNAs, from at least five different crops, and expects to find many more. Just more news to chew on, while you ruminate over your afternoon snack.

Saturday, September 17, 2011

Musings: Who are Chemists, Anyway?

When I’m performing a repetitive lab task (columns, iterative dilutions, etc.), my mind tends to drift. Yesterday, I began thinking about who I actually work with, where they come from, and why they’re in chemistry. Ever heard Jeff Foxworthy perform “You Might be a Redneck if…”? What if someone were to compile a similar list about synthetic chemists?
Thus, a few observations, from the subset of, say, 300 chemists I’ve worked with over the last ten years:
"It's OK, Dom, I'm leaving baseball for grad school"
Credit: AP
They tend to be older siblings: Perhaps there exists out there somewhere a biotech run entirely by younger sibs, but I haven’t found it yet! At my current job, all senior managers are the oldest siblings in their families, and I’m fairly certain most of the bench chemists have younger brothers and sisters. Maybe the old nature / nurture debate surfaces here, where parents encourage older children to pursue medical and scientific careers.
Folks come from all over: I hail from a town that the 2000 Census dubbed >95% Caucasian. Many of my friends went off to school, and then moved immediately back to town. After college, I moved 700 miles away, possibly to escape this exact fate! This "lifestyle inertia" has never occurred at any of the six labs I’ve worked in: the scientific population integrates well (math joke here?). My coworkers have hailed from all over the US, plus every continent except Greenland. It’s fun to watch Russian postdocs tell jokes to Indian coworkers, while French, Chinese, and Iranian labmates listen in and laugh.
Tech-savvy:  The first Blackberry I ever saw was wielded by a chemist. Ditto iPads, USB sticks, and noise-cancelling headphones. In grad school or college, you’ve probably used MacOS, UNIX / Linux, and most of the Microsoft Office suite, and you may have created .pdfs, manipulated graphics files, or solved crystal structures. It comes with the territory.

Merit badges = Future PhD?

Be Prepared? Four of my former coworkers were Eagle Scouts, and several more have EMT and First Responder training. Safety first.
Hobbies? Try second careers: Bench chemists live two lives: they’re passionate about their chemistry, but everyone has a hobby that they could fall back on (maybe a necessary practice in a bum economy). I’ve met semi-professional musicians, day traders, lay pastors, auto mechanics, authors, aerobics instructors, economists, coaches, show promoters, bodybuilders, shop owners, and even professional dancers.
World Travelers: Maybe this makes sense given their international background, but chemists travel all over. Many save up their whole vacation allotment for 2-3 years, and then go to China, France, Australia, or Argentina. Back when large chemical concerns had travel budgets (I know, a novel conceit), chemists could rely on at least one expedition per year, usually to attend a big conference in a far-flung locale.
Not Fashion Plates: You won’t see many chemists dressing like the men and women striding down docks in J.Crew, or taking nighttime strolls like they do in Ralph Lauren catalogs. Perhaps it’s thrift, or comfort, or maybe chemists just realize that their clothes have limited lifetimes in synthetic labs.
Office Pool?  Of course!  Chemists tend to jump at opportunities to participate in NCAA tourneys, fantasy football, or poker nights. Maybe it’s the competition? The odds? The logic? Who knows! I’ve worked in labs where two competing tournaments have been run simultaneously…and both found plenty of participants.
Wanna join our league?
One-Upsmanship: Many of the conversations I’ve had with older chemists invariably come down to competitions over how hard the job once was. Usually, they begin with “Oh yeah? Well, when I was your age, we had to recrystallize everything to purity, we didn’t have working fume hoods, and we actually used the (insert here name of old, dusty apparatus in the corner no one ever uses).” Maybe this speaks to how much synthetic chemists enjoy competition (see above).
War Stories and Battle Scars: No, I’m not talking about actual military service, although I’ve worked with a few chemists who have bravely fought alongside our troops. I refer to tales career chemists always tell at bars, stories where pump traps explode, flames shoot up from flasks, and injury was narrowly avoided. If you work in a synthetic lab long enough, you’ll have a few close calls, and you might even have something to show for it: a bald spot here, a burn there, even some stitches now and again.

Thursday, September 8, 2011

Come On, Allene! The Crabbé Reaction

Readers: This post was written in response to Rachel Pepling’s call for submissions to the IYC2011 Chemistry Carnival over at CENtral Science
Have you ever been in love?
Has a single, chance moment changed your outlook on life?
Did you ever have the burning desire to . . . add one little methylene group to the end of an alkyne?
I’m an organic chemist, and our emotions tend to track directly with the success of our bench work. In my third year of graduate school, I felt down in the dumps.  My methodology project had no traction; heck, I couldn’t even make the (relatively simple) allene substrates I needed in less than five steps! Such was life when, during my group meeting presentation, a voice chimed in from one of the postdocs sitting in the far corner of the room:
“I think there’s a reaction for this.  Haven’t you tried the Crabbé?”
(At first, I stared agog, since the name made it sound like he was ordering seafood in a fancy French restaurant, so I thought he was joking, but he wasn’t!)
Turned out, there was a “chemical shortcut” to do just what I needed: the Crabbé takes a terminal alkyne under Mannich-like conditions (di-isopropylamine, formaldehyde, dioxane) – with a dash of copper (I) bromide for good measure – and adds a methylene (=CH2) unit to form an allene (see scheme). Why make allenes, you ask?  The two alkenes in this three-carbon synthon are orthogonal (at a 90o angle), which twists their pi-electron clouds away from one another. Thus, each olefin can react independently in reactions like metal coordination or electrophile addition.
The reaction mechanism made me scratch my head for a while, just as it did Crabbé’s researchers working at U. Missouri in the early 1980s. These chemists propose that, after the initial Mannich adduct forms, a copper atom wiggles into coordination between the amine and the alkyne. When you crank up the heat, the amine kicks out a hydride (H-) from an isopropyl group, which then migrates to the copper. This copper hydride spins around, delivers its hydride payload to the alkyne, and kicks out an imine leaving group. 

Credit: Carl Sagan's Dance Party Blog

It’s a fairly chemoselective reaction, meaning you can use it late in the game in a synthesis (assuming your compound can survive heating in dioxane for a few hours with copper!). My favorite part? I enjoy watching the autumnal palette that evolves during the reaction, from birch-tree yellow to maple-leaf red. Different starting materials lend different shades. And, as most organic chemists will tell you, one-pot preps you can set up and forget about are the reactions we love.

Links and Such

A few recent internet chemistry items for your viewing enjoyment:

Paul is already hard at work predicting October's Nobel Prize in Chemistry.

Chemjobber waxes on vacation requirements (or not) in academic labs.

Hey look, nitrogen particles!  Wait, no, that's snow...
Over at Forbes, Matt has a profile of Peter Hirth, the man behind Sutent and Zelboraf.

Ivan Amato chats up horseradish and pain receptors in the Washington Post.

NPR's Morning Edition covered a recent Nature article, but what the heck is a "nitrogen particle"?