Vacuum Pumps 101

May I present to you the humble vacuum pump:

Credit: Ideal Vacuum

Credit: Ideal Vacuum

We chemists tend to not give them much thought, which is a shame seeing in that we work with them daily.  Much of our work depends on being able to lower the pressure of a system for whatever reason.  Want to evaporate solvent?  Your membrane diaphragm pump has your back.  Want to distill an irritatingly high-boiling off-yellow mixture to your pristine colorless product?  Look no further than your trusty rotary vane pump.  Need to shoot your compound onto a mass spec?  The instrument’s turbo pump creates the ultra high vacuum environment required for accurate analysis.

I could go on.

Despite the ubiquity and utility of vacuum pumps in the chemistry lab, the trend I’ve noticed is that most workaday chemists know little to nothing about how they work and how to take care of them.

[Screaming Internally]

“Steve, this says the last time you changed the pump oil was April 2014.”

As a result of this ignorance around pumps, I propose all chemistry degree programs, at both the graduate and undergraduate levels, teach a mandatory class on vacuum pumps.  I submit for your review a syllabus outline for this class:

Vacuum Pumps 101

  1. Introduction to vacuum pump types: How to tell a rotary vane from a diaphragm pump
  2. When to use a vapor trap: Always
  3. Oil changes: Coors Lite = good, Guinness = bad
  4. Handling acid vapors: How to destroy a pump
  5. Quiz: What is that sound?
  6. Gas ballast use: Why is my pump oil in two phases?
  7. Lab practical: Why are there leftover screws?

So maybe it’s seminar series or a 2-credit class.  Upon completion, students are given a license to use rotary vane pumps.  The lab practical will be graded pass/fail, with failing students relegated to using old rotary evaporator diaphragm pumps.

 

Why do we say that?

We chemists love our jargon.  Oftentimes for good reason; it would be cumbersome to describe a material as “having a tendency to absorb moisture from the air” over and over again.  Instead, the word hygroscopic gets the point across succinctly.  Examples of this sort of jargon abound, with the IUPAC Gold Book defining some 6400 unique terms.

The type of language that’s used in the chemical literature actually gives us a window into the work being done over time.  A while back Stu compiled 115 years of JACS article titles into word clouds binned by decade.  The result?  A visual representation of a century of chemical research.  While you see words like “synthesis,” “stereochemistry,” and “nano” reflecting changes in research interests over the years, you also see steady usage of words like “new,” “efficient,” “direct,” and “novel.”

This brings up a second set of chemistry jargon terms which generally do not describe specific and well-defined concepts.  Instead of jargon, one might just call these terms adjectives common in the chemical literature.  We like to poke fun at the use of words like novel, concise, and robust.  Who gets to decide if a preparation is concise, or if a given synthesis is more or less robust than those that preceded it?   After all, there’s more than one way to talk about synthetic efficiency.

Bringing me to my topic du jour, just today I came across the umpteenth paper ascribing the mechanism of a particular reaction to the “steric and electronic properties” of the starting materials.

sterics

16,000+ results, see I’m not crazy

What other kinds of properties can reactants have?  Aren’t all properties just emergent from either sterics or electronics?  The chemical-reductionists among us would argue that all properties are emergent from quantum mechanics anyway:

It’s not factually incorrect to say that a reaction behaves the way it does because of sterics and electronics, but that description could apply to literally every reaction.  Find me a reaction mechanism that isn’t governed by S&E, and we’ll talk.  This kind of language treads dangerously close to the territory of the not even wrong.

The S&E argument, like many other broad but factually true statements from the literature, is in all likelihood just a euphemism for “it is what it is.”  Maybe it’s time to assemble a list of useless phrases for a literature bingo game…

“Those who can, publish. Those who can’t, blog.”

There’s a Q&A piece in Current Biology (a Cell journal) on Professor Jingmai O’Connor circulating at the moment.  Most of it it pretty standard stuff: Why are you a biologist?  What’s it like being an American scientist in China? What was your favorite conference?

But for a “young scientist,” two of O’Connor’s answers sure seem old school. One question asked of the professor was “Do you think there is an increased need for scientists to market themselves and their science as a brand?”  Her answer (emphasis mine):

I think the idea that scientists need to operate more like a business is becoming a major problem in science recently. There is science and there is business — they are different and should be fundamentally driven by different goals: one, the pure and unadulterated desire for greater knowledge and the other, monetary gain. Branding science puts focus on making your research appealing, which is extremely limiting, and — dare I say? — corrupts the scientific process. There is a lot of fundamental research that needs to be conducted that is not ‘sexy’. Such ‘science branding’ has not yet affected the Chinese Academy of Sciences and for that I’m grateful.

Ignoring how pretentious this comes off as,  the idea that making  your science “appealing” somehow corrupts it is exactly wrong. Science should be appealing. If your science isn’t appealing, maybe you’re not doing good science. And second, the idea that business and science are mutually exclusive enterprises is laughable. I can point to dozens of fundamental scientific discoveries made by the private sector. It turns out that money is actually a pretty good motivation for coming up with cool new scientific ideas. Conversly, let’s not pretend that all science is driven by “the pure and unadulterated desire for greater knowledge.” This implies that only academic science is true science. But even academic science has a driving force that is decidedly non-scientific.

It gets better (worse?) from here. “What’s your view on social media and science? For example, the role of science blogs in critiquing published papers?

Those who can, publish. Those who can’t, blog. I understand that blogs can be useful in affording the general public insights into current science, but it often seems those who criticize or spend large amounts of time blogging are also those who don’t generate much publications themselves. If there were any valid criticisms to be made, the correct venue for these comments would be in a similar, peer-reviewed and citable published form. The internet is unchecked and the public often forgets that. They forget or are unaware that a published paper passed rigorous review by experts, which carries more validity than the opinion of some disgruntled scientist or amateur on the internet. Thus, I find that criticism in social media is damaging to science, as it is to most aspects of our culture.

Damn kids, get off my lawn!

That’s a real doozy. The last part reads like that guy who is proud of not having a Facebook account like it’s some sort of accomplishment. But all snark aside, I strongly disagree fundamentally with what O’Connor has to say about blogging and social media with respect to science. I can point to example after example of successful, productive scientists with active social media presences. Again, the two are not by any means mutually exclusive.

But perhaps my biggest problem with this response is how brazenly the author dismisses public criticism and post-peer review in favor of the almighty peer review process.  As if nothing shady ever gets by peer reviewers. If you publish something in the scientific literature, you’re putting your work out there.  You’re making claims, and you shouldn’t be surprised (or offended) when challenges are made to what you’ve said.  Because challenging the status quo is exactly how science works, whether it’s in a subsequent publication, a blog, or on PubPeer.

Non-“Breaking Bad” methamphetamine

Oh dear.  Well, It didn’t think I’d have cause to write about methamphetamine production again, but here we are.  Many readers will have heard news about the explosion that rocked the NIST lab near Washington, D.C. back in July.  Luckily, no one was seriously injured; but one security guard did sustain some burns.

No more than a couple days later, initial investigations revealed the cause of the explosion appeared to be… methamphetamine synthesis.  Now, any competent chemist in a national lab would (hopefully) be able to perform any of the common meth syntheses without incident.  Certainly without blowing the windows out of the building and hospitalizing his or herself.

But as it turns out, the culprit wasn’t a chemist, but the security guard injured in the blast.  More details have been emerging since the incident.  After resigning from the force, the guard in question pled guilty to attempted methamphetamine manufacture.

It turns out the method the guard was attempting to employ is that known colloquially as the “Shake and Bake” method.  This involves reduction of pseudoephedrine to methamphetamine, then treatment of the reaction mixture with hydrochloric acid, forming a salt which is easily separated.  And in true MacGyver style, the reagents used in this reduction are all improvised: camping stove fuel as a solvent, lithium from batteries, lye, and ammonium nitrate (fertilizer).  HCl is generated by the action of sulfuric acid (sold as drain cleaner) on table salt.  Literally everything you need can be purchased at Wal-Mart.

And what do we do with these reagents?  Why, toss them in a water bottle, close the cap, and shake, of course.  You can’t hear it, but I’m actually screaming behind my keyboard.

The idea is you vent the bottle, as a good amount of gas is going to come off of that particular reaction.  The reason people use this method to make meth, aside from easy access to the starting materials, is that it can be done on a very small scale: a few grams.

What I don’t understand is why, if you’re going to illicitly make methamphetamine in a synthetic chemistry lab, you decide to bypass all those fancy solvents, reagents, glassware, and safety equipment.  Maybe they were worried someone was taking inventory of the reagents they’d need?  In my experience, it’s highly unlikely anyone was.

Instead of doing some homework and using the lab equipment that was already right there, they opted to go straight to the basement-bottom chemistry.

And again, I can only speculate as to exactly what caused the explosion (chemists: take your pick of things that could go wrong with that procedure), but I’d put money on overpressure in the “reaction vessel,” resulting in rupture, and exposure of lithium to air.  That would likely generate enough heat to ignite the expanding camp-fuel-solvent cloud.  And ka-boom.

I’ll take “Syntheses I won’t attempt” for 500, Alex.

 

On making pretty structures

I had an exchange with @fluorogrol today talking about poorly thought out chemical structures.  It began when the pseudonymous blogger tweeted out the (less than optimal) structure of this alkaloid:

Wrong, indeed. Representing complex stereochemistry can be quite tricky.  But bonds extending halfway across the molecule is generally not the way to go.  Chemical structures must satisfy two requirements: 1) they must be unambiguous, and 2) they must accurately represent the 3-dimensional shape of the the actual molecule.  I responded with my take:

…which was straightened out and rotated a bit, giving us this final, unambiguous structure:

No exaggerated bonds, no stereocenters consisting of a cluster of wedges.  Plus, now you can quickly get an idea for the actual shape of the molecule.  Now, admittedly, I have no idea where the original structure appeared, but I’m going to assume it’s from a publication.  Which means a group of scientists, and presumably at least one organic chemist, collectively decided that structure was the best way to represent akuammine (the wikipedia page structure is equally bad).

And to think, this tragedy could have been easily avoided.  Here’s a quick checklist on how to draw an accurate, sexy structure of your molecule.

1) Does the molecule have any cyclic or bicyclic motifs common in organic chemistry?

To list a few...

…to list a few

If yes, start there.  These structures are so ubiquitous in organic chemistry that they give readers a quick and easy 3-D reference point.  Not sure if there’s one of these in your molecule? Proceed to step 2.

2) Load you molecule up in the three-dimensional molecule viewer of your choice.  The professional edition of ChemDraw comes with Chem3D, which will do the trick.  As will whatever you may use for energy calculations.  Don’t have access to any 3D chemistry software?  MolView has you covered with its in-browser tool, which can even perform simple energy minimization calculations.

Rotate the structure around a bit.  Look for any of the aforementioned motifs.

Picture1

Still can’t find one?  Then…

3) Find and angle from which all atoms are more or less visible.  Of course, your ChemDraw structure doesn’t need to perfectly match all bond angles and distances, but try to replicate them as faithfully as possible.  A good angle is one from which stereochemistry is unambiguous and doesn’t require dashes and wedges everywhere to makes sense of the structure.  Also, don’t forget the ever underutilized “structure perspective” tool in ChemDraw; make judicious use of it.

Maybe I’ll start featuring a “bad structure of the week” here.

Strain energy for days: an in silico study of xinghaiamine A

SeeArrOh (via Twitter) reminded me of something I’ve been wanting to check out since this paper surfaced.

The paper in question features a supposed natural product, named “xinghaiamine A,” with some pretty wonky bonding.  Readers at Just Like Cooking and In the Pipeline brought up some issues regarding the evidence for this compound’s existence.  And rightly so; there appears to be something off about the supplemental data¹.  But, ignoring the (very real) issues readers have brought up with the supporting info for this paper, just look at this structure:

Oh dear

One half of the proposed compound.

At first glance, there’s some serious strain going on in there.  I figured I’d take a look at what xinghaiamine A looks like in 3D-space.  Getting it to behave in Spartan was a challenge on its own.  Chiefly, that bicyclo[2.2.0]hexane system was quite problematic.  Initial geometry optimizations at the semi-empirical level of theory produced some odd results.  I ended up settling on MMFF geometry optimization, which gave me the reasonably acceptable structure shown below²:

MMFF geometry optimization

MMFF geometry optimization of the xinghaiamine A “monomer”

Check out that bowl-shaped aromatic system.  That thing is supposed to be planar.

Check out that torsion angle: 40 degrees!

A torsion angle of 40 degrees.  And how!

The next logical step is to figure out exactly how much strain energy is in this thing.  This was done by taking the MMFF optimized geometry of xinghaiamine A and using it as a starting point for Spartan’s “T1 thermochemical recipe.”³  The T1 recipe is a post-Hartree-Fock method which consists of:

  • A quick and dirty HF/6-31G* geometry optimization
  • MP2 single point energy calculation with expanded basis set

This set of calculations yielded a heat of formation for xinghaiamine A of 1098.65 kJ/mol

Now, if we break that C-C bond joining the acenaphthalene and the bicyclo[2.2.0]hexane systems, repeat the calculations, and compare the results we can get a pretty decent idea of how much strain energy this proposed structure contains:

That planar acenaphthalene system looks so much happpier

That planar acenaphthalene system looks so much happpier

The answer is: a lot.

Breaking that one bond liberates quite a bit of energy.  But that’s not what makes this structure so implausible.  No, as others have pointed out, some of the motifs in this molecule have never been seen in a natural product.  And if you’re going to propose something never-before-seen, you best have the evidence to back it up.

Which raises the question: did the authors think the chemistry community would look at that structure and collectively go “yup, looks good to me, moving on then”?


  1. Something that rhymes with “fata dabrication”
  2. Note: the published structure is a dimer.  I’ve modeled it as a monomer, with a methyl R-group for computational simplicity
  3. Not a shill for Spartan, I promise

Reporting Adverse Results in Publications

Here’s a question: to what extent should authors describe the limitations of their results in publications?

I’m not talking about failed experiments and negative results or null-hypotheses.

For example, say a compound is synthesized, but is highly unstable in air, causing it to decompose rapidly.  Should that be noted?  Or maybe someone makes a new polymer that undergoes depolymerization after a couple days on the bench.  Should the researchers describe that in their publication?

Of course, it’s contextual.  Does the negative observation directly impact potential applications of the material?  If yes, then one would think it imperative accurately describe the limitations of research, especially if they are known at the time of publication.  It seems irresponsible to intentionally leave out these details.  And it is exceedingly frustrating as a scientist to discover these sort of details independently, when replicating others’ results.

Obviously, it hurts your chances of getting into a high impact journal if your results are muddled by adverse circumstances at the back-end.  And not every single negative result is noteworthy.  Library synthesis papers don’t describe every single failed substrate, but they often note something along the lines of “[class of compound] did not react to produce the desired product.”

I don’t have a perfect answer to this question.  Thoughts are welcome by comment or email.