Showing posts with label GC. Show all posts
Showing posts with label GC. Show all posts

Sunday, July 17, 2016

Undergrad Tech: Remember When?

Recently, I sat with a friend sipping coffee, watching passers-by hurriedly moving from one tall building to another. Remarks drifted back towards research - as they're wont to do when chatting with chemists - and she said: "Remember how hard it was just to order things?"

I knew exactly what she meant. Lab tech changes quickly, and you may not even notice until you take a step away from the bench. I'm not part of the generation who spent hours sketching molecules by hand from a rubber template pre-ChemDraw, but nor am I a grad student in the era of tablet computers that can access PDB or Aldrich from a free wireless connection in any lecture hall.

Maybe I'll take a quick stroll down memory lane to see how different things really were when I first started undergraduate research...

Planning: Then, as now, most projects kicked off using pen-and-paper or chalkboard sessions; whiteboards were in about 30% of classrooms and gaining ground, but my first experiences with drawing molecules for my coworkers covered my fingers in tacky powder. I can still smell lab chalk: musty, earthy, sometimes tinged with a faint amine odor if stored too near the reagents cabinet.

Courtesy of Dr. Freddy, at Synthetic Remarks, who seems to recall
chalkboards much more fondly than I.

Once you'd had the discussion, you transcribed it into a lab notebook - usually bound with black vinyl, perhaps featuring brown or maroon faux-leather accents and a bookmark string - and signed the page. Then it was time to dive into the literature. First, you staked out some territory at one of the few hulking beige monitors attached to your shared lab computers. Plan for coffee, since reboots and blue-screen crashes could usually be expected to last 10 minutes, with accompanying Windows jingles or goofy Mac cursor wheels.

(Why were operating systems always a generation behind on shared computers?)

Your 10-minute excuse to go grab a coffee.

Beilstein and SciFinder both offered installed systems with single-user seats. This meant you walked down your lab hallway, shouting "Does anyone need anything on SciFinder?" before logging in. The user interfaces were very Internet 1.0 - muted grey windows, inscrutable black text, fuzzy structures. Mostly, you would up transcribing the reference into your notebook alongside the idea. To get the paper, you usually brought a stack of dimes down to the reference library, and spent the next 20 minutes finding and then copying (don't forget to rotate every other page!) the journal article. The still-warm, toner-scented stapled copies were lugged back to your wooden desk to be pored over until evening. My fingers would often be tinged with more than one color of highlighter or colored pen after a night of intense study.

SciFinder Scholar, 1999. Source: ISTL.org

Synthesis: OK, you know what you want to make, so you need some reagents. Maybe first you glanced through the 2,000-row Excel file your lab has as its de facto "inventory" system. I remember some groups also had a dog-eared, yellowing notebook dangling from a rope of masking tape that listed all the chemicals no one needed any longer - hope you enjoy distillation! Failing these approaches, the trusty catalogs are all lined up against the single lab window, effectively blocking out 20% of the available visual real estate. Names of vendors I remember included Fisher, VWR, Aldrich, Sigma, TCI, and Columbia. Each one had different account reps, pricing, and delivery specs; you'd better believe your boss would ask if you looked up pricey, boutique reagents in more than one source. Someone had the lab job of calling these vendors every few days, providing the lab P.O. number or group credit card, and then taking delivery later that week. Collections of cardboard boxes large and small would be piled near the front door, and every week was Christmas (even if it was just your reagent-grade TEA).




The first and last physical Aldrich catalogs I remember ordering from.
Source: Alfred Bader, Sigma-Aldrich
At some point, you'd have everything needed to run your experiment. Hours passed, TLCs ran, and you scribbled long-hand in that same lined lab notebook. I'm fairly certain I spent thousands of hours hunched over, detailing exactly how the workup went, or scrawling single-line corrections (with initials!) for changes and errors.

Analysis: Instruments fell largely into two camps - things you ran and printed out to later affix into 3-ring binders, or numbers on an LED screen you hastily scribbled onto a Post-it note. UV-Vis and optical rotation fell into this latter camp; I still smile whenever I see a forgotten, tucked-away bookmark reading "+8.75 deg."

I worked in lab right at the death knell of chart-recorders - little red pens in threaded holders that traced a curve based on numeric readouts from an IR or GC. NMR, graciously, always emerged on an ink-jet printer in the corner of a sub-level lab. I was a Bruker shim-jockey for quite a while, bragging that I could shim, acquire, FT, pick, and integrate an 8-scan 1H in under 2 minutes. Of course, many academic labs now have robotic cherry-pickers and automatic data transfer, which must save tons of time (unless you're a biophysicist or monitor kinetics; we might as well chain you to the 600MHz).

Source: Cal State LA / Bruker Instruments

Presentation: My first lab group still owned an overhead transparency viewer, and we were encouraged to print or sketch acetate slides each week for discussion. As these smudged easily when warm or done hastily, there were many grumblings and thrown elbows at the photocopier from fellow labmates on group meeting day. PowerPoint was reserved for "big" talks - oral exams, defense seminars, or preparing a poster for ACS meetings. Once saved and laid out the way you wanted, these were burned onto a CD-R or stored on a 100MB USB flash drive your boss might loan you. The walk to FedEx felt tense, because you didn't want to lose this uncomfortable piece of plastic, which contained the only copy of your slides.
Just don't write on the glass itself, or the PI will get really angry. Trust me.
Source: Amazon

I'm sure that I'm missing more fun events from lab life and technology from the late 20th century. Readers, if you have a special memory from back in the day, please feel free to share it in the comments. I'll update the post if I've missed something vital.

Saturday, April 27, 2013

#ChemMovieCarnival: Closing Credits

Missed 'em? See Day 1, Day 2, or Day 3!

[Cut! That's a Wrap]

The sun's setting on the final day of filming. Champagne flutes float around, and cast and crew celebrate another one "in the can." Who wants to help strike our #ChemMovieCarnival set?

24. Over at Chemtips, Brandon accidentally spills some "Hollywood Acid" on the floor, and watches as it eats all the way into the basement. Beware the Dip! Seriously, though, he give great advice on handling and care when using straight HF. Bonus points for using an Adult Swim cartoon clip to prove a scientific premise.
Movie: Who Framed Roger Rabbit?
TV Shows: Breaking Bad, Robot Chicken

25. In a valiant second effort, Vittorio tells us more about his favorite crime procedural, NCSI. They apparently have a super-cool mass spectrometer capable of labeling individual components - despite them occurring at the wrong masses. "Non-Chemist Ion Spectrometer," indeed!
TV Show: NCIS

26. Speaking of wonder instruments, Jim emailed me a fantastic guest post about James Bond doing drug discovery. In the rain forest. With a "portable GC." Cure for cancer sure to follow...
Movie: Medicine Man

27. ChemBark sends over a favorite clip of Martin Sheen acting presidential, and apparently pulling a one-liner out of his hat for...table salt (N-A-C-L, CJ). Kary Mullis, for the record, was probably LOTS of fun to sit next to, if Paul's memory serves.
TV Show: The West Wing

27a. ChemBark bonus - A show forever welcome on this blog, where an English a French starship captain confesses he flunked O-Chem.
TV Show: Star Trek:TNG

[Update, 4/28] 28. Jeez, Vinylogous! The door had nearly shut, and you had to go post this gem from a long-running NBC sitcom about a struggling paper company. Bonus: eyewash humor!
TV Show: The Office

Thanks to everyone who made this a great carnival! 
As they say, see you at the movies (hopefully with a better scientific advisor).


~Fin~

#ChemMovieCarnival Guest Post: Jim Explores the "Science" in Medicine Man

A few nights ago, a random Twitter encounter led to a fantastic email submission from Jim Leahy, who goes by @usffan. As Jim points out, the Sean Connery vehicle Medicine Man contains some laughable chemistry moments (note: I've lightly edited for style and linkage, but it's otherwise untouched):

***


When I saw See Arr Oh’s #ChemMovieCarnival, the first movie that popped into my head was Medicine Man, a 20-year old movie that I recall prompting many belly laughs.  To set the stage, this is how Netflix (which rates it as a 3.5/5 star movie!) describes it:

Reclusive scientist Robert Campbell (Sean Connery) discovers a flower extract in the Amazon rain forest that cures cancer. He tries to duplicate the life-saving formula, but clear-cutting developers and American bureaucrat Dr. Rae Crane (Lorraine Bracco) hinder Campbell’s efforts. When a native child falls ill, the scientist must decide whether to save one life with the last of the serum or keep it for further analysis.”

James Bond AND a flower extract that cures cancer? 
What could possibly go wrong? (well, other than not wearing protective eyewear?)

I was disappointed to find that Netflix doesn’t offer the movie online, and when somebody pointed out on Twitter that Derek Lowe’s very first post on In the Pipeline was about this movie, I thought about just skipping it. Fortunately, I found that the entire movie exists onYouTube, and decided that it really needed to be a part of any #ChemMovieCarnival.

For the sake of anybody who wants to watch the movie, I’m not going to spoil any significant plot points. This is just about the “science.”

The two scientists involved in the movie are a botanist (Robert Campbell) and a biochemist (Rae Crane) who has “degrees from CCNY, Berkeley and Cambridge and is the only person to win the Thurman Award twice.” Campbell has been working in the Amazon rain forest for years, being supported in his research by Aston Pharmaceuticals and has asked for a new research assistant as well as a gas chromatograph. Crane makes the significant journey into the rain forest (including a pretty extensive hike and a canoe ride) with the GC in tow to reach Campbell’s makeshift lab (presumably, vendors such as Agilent and Perkin-Elmer don’t ship to the rain forest!). When Crane arrives, it’s night time and Campbell is pretty hammered (no telling if the drinks were shaken, not stirred). So Crane sleeps for the night under a tree. This is where the scientific fun starts.

The next morning, when she wakes up, she discovers that Campbell is starting to unpack the instrument, which he miraculously has up and running within minutes. My first thought was “wait, what are they using for carrier gas?” although later in the movie there’s a shot of tanks and regulators (AirGas apparently does deliver to the rain forest). After some banter, Campbell asks Crane “what am analyzing?” which she answers with the question “did you run a baseline?” Not sure how that would help answer exactly what Crane is analyzing, but it’s good to know that the biochemist is keenly aware of standardizing the instrument. And what an instrument it is!

Campbell has injected a sample into the GC, a partial trace of which looks like this:


As Crane starts to examine the chromatogram, she discovers that nearly all of the compounds are “known” 

For those of you who understand gas chromatography, you know that a basic requirement is that compounds have to be sufficiently volatile that they can be converted into the gas phase before they can be analyzed for retention time along a column, which makes the instrument’s ability to vaporize silica, sodium phosphate, sodium nitrate and ferric chloride pretty remarkable, especially in light of the fact that it’s an older model GC. Frankly, I’m much more impressed with the compound coming off as peak 39. Remember, these are all the unremarkable “known” compounds, according to Crane. I’m pretty sure finding NaCl2 at all, let alone in nature, would be worthy of publication in Science or Nature. Which is when you start thinking “wait, how are they identifying these compounds?” Remember, this is just a GC – what kind of detector are they using that identifies all of these inorganic compounds? We’ll come back to that…

Campbell seizes on the words “nearly all,” which leads them to focus on peak 37, which isn’t apparently “known." 

Clicking on the peak reveals the structure of peak 37 to be:


Sorry, I couldn’t get it to come into focus any better than that, but it’s the best view of the entire molecule in the movie. They do have a partial shot that allows a little better view of some of the details:

Where to start! Apparently this GC has the ability to determine structures of unknown natural products, which would really come in handy, although to be fair, it doesn’t seem to be able to distinguish stereochemistry, and I count at least 8 stereocenters in this partial shot of peak 37. Then again, those stereocenters are insignificant compared to the two Texas carbons in the bottom ring. Crane marvels that “it’s an acid derivative,” which I can only assume refers to the side chain that’s partially cut off in the close up but appears to suggest that the alcohol (which may be stereocenter #9, by the way) exists as a bicarbonate. Campbell’s only concern is whether it can be synthesized, to which biochemist Crane replies “uh-uh, it’s Mother Nature’s kitchen sink.” Apparently the biochemistry program at Cambridge includes an extensive synthetic organic chemistry component.

It turns out that peak 37 appears to be the “cure for cancer.” I would sure love to know the pharmacokinetics of this compound which may be competitive with the least Lipinski-like small molecule to be considered for clinical trials. Lots more scientific comedy ensues, such as the ability of a botanist and a biochemist to apparently diagnose lymphatic cancer, but a few highlights include their formulations expertise at finding a suitable injectable of the extract and the stunning response time that comes from a single dose of 37. I also suspect that the FDA would not take kindly to the human testing of most assuredly non-GMP material.

None of this should keep you from watching the movie (although the 24% on Rotten Tomatoes might), and I suspect that there’s lots more scientific comedy to be mined here. Either way, it deserves a special spot in the #ChemMovieCarnival.

(Thanks, Jim! Great post. -SAO)