Friday, January 9, 2015

Revisiting grad school and mental health with Chemjobber

Note to readers: this post is a response in a dialogue between Chemjobber and I on grad school and its effects on mental health. Yesterday's post can be found here.

Dear Chemjobber:

It has indeed been awhile since the last mental health dialogue. Since then, I've gained additional perspective from inside grad school, and it is invaluable to hear your view from "the other side." Hopefully some of the observations and recommendations below will be of interest to you and perhaps to readers.

Last time we talked about this topic, I was significantly earlier on in my grad school career. Since then, I've had battles: dealing with failed multi-month projects, going through intense candidacy preparations, attending to seemingly overwhelming (at the time) departmental milestone requirements, wondering if every experiment that worked was just me fooling myself, adjusting to being several states away from family and my SO, and wondering if my PI knew enough to steer my career in a productive direction.

Early on, it was easy to get discouraged. Now, it's still easy to get discouraged. That's research, I guess. Part of my struggles entailed coming to terms with the fact that I did not want the job I originally came to grad school for: academia. Moreover, I saw college and high school friends rocket past and start exceptionally successful careers in other discplines, and I have seen other people I regarded as lazy or duplicitous get showered in accolades in their fields. That kind of thing--comparing yourself to people in different career paths--is rough. And when you've sunk 8 years into your university education, it makes changing career trajectories stressful and confusing.

More than once, due to a culmination of these things, I came to the brink of leaving the grad program. As it happens, I didn't. More on that a little later.

Defining Mental Health

In the last two years (and maybe it's just confirmation bias, or increased vigilance on my part due to our earlier dialogue), mental health has received a lot of press (particularly in regards to crime and rationalization of gun violence).

I think that makes the subject a bit taboo--as if admitting to problems is akin to saying you're an unstable risk.

Before I write further, I want to articulate what is meant.

Having a problem with mental health doesn't have to mean severe mental illness. It is a strain on emotional and/or cognitive well-being. It doesn't have to mean severe depression. It can--and that's common--and it's okay.

This is the best way I've heard it phrased: every single person on Earth has some degree of mental health issues. And so it pays to have empathy.

For fear of feeling weak or being stigmatized--or simply due to denial, or thinking that the situation isn't serious enough, or that care is too expensive--many people don't get help for mental health problems. And, again: "problems" can range from crippling depression to simply feeling overwhelmed with expectations at work. Either way, it behooves one to be introspective and take advantage of help that is available, as wellness is infinitely more important than pride.

Has Grad School Changed?

You asked about change in the attitudes and policies of professors in grad school: are more (younger) professors opening up about the mental health/stress needs of students? Is "work/life balance" more of a serious consideration and less of a joke? Or is it status quo?

This is one of those questions that it's hard to address in any more than an anecdotal manner. I want the answer to be "yes--new professors are generally more socially and emotionally in tune and respect their students' time and needs". I think that to some degree that is the case, but it's very, very group-dependent. Many (relatively newer) PIs that I've seen don't religiously track hours and do encourage students to have outside hobbies. But since being a PI is still stressful, science academic culture is still a place of forced machismo, and research grant funding is still scarce, I also see many new PIs work their students much harder than average (while being groomed to do so by more senior faculty).

Here's my rule-of-thumb diagnostic that can be applied to PIs: what do they think (and how do they respond) when a student has no interest in going into academia? It's a rather simplistic way of viewing it, but many of worst professors in this regard are the ones who view anything other than an academic position as failure. Other PIs (often when both young and not purely synthetic-oriented) accept that academic positions are a minority and that life is a balance of priorities and different students have different needs. This latter category is, I hope, becoming more common.

Hopefully dialogues such as these (and the accompanying discussions we saw last time) at least serve as consciousness raising to spur dialogue between students themselves and between PIs and their labs.

Behavioral Pitfalls and Mental Health and Dealing with It

The last two years have given me some time to reflect and also observe--and it seems that certain combinations of behaviors and attitudes are especially bad, mental health-wise, in the context of grad school. But there's also ways to deal with them. For instance:

Avoid burnout: Some people are prone to starting projects fervently, working on them vigorously for long hours. That kind of work ethic--an almost obsession--can be immensely productive in the short run, but people who do this also tend to burn out really quickly. In jobs where projects switch frequently (maybe graphic design, or consulting, for instance) this might be sustainable.

Grad school, however, requires a slower burn. Long hours are expected--but they have to be tempered. What's the key, then? I think you have to set in for the long haul and learn what your limits are. Find the burn rate at which you're energized but not drained.

Of course, that's easier said than done. But as far as I can tell, the people most prone to burnout have a tough time adjusting mentally to graduate school.

On a related note, make sure to have some hobbies. People without hobbies adjust more poorly to stress. Do things, read things, create things, eat things, etc. Learn a language or something.

All too often people lose their hobbies and interests in grad school. That's easy to do. I've experienced it--I used to play quite a bit of music at what (I think) was a decently proficient level. That's all but stopped. I used to write a lot--and read a lot, too. The consuming nature of grad school, however, tends to leave your evenings consumed by reading literature, napping on the couch, or just generally decompressing. Or running columns (although--honestly--rarely is a column so important that you have to run it at 6 pm; if you do that frequently, chances are that you're just running away from having to do something else in your spare time that might make you an interesting person).

So hobbies take effort. But so does exercise, and building relationships, and preparing nontoxic food, but they're worth it, and very important.

If your labmates or PI ridicule you for having serious outside hobbies (such as coaching a sport, leading church discussion groups, running, brewing beer), then don't work with those people. Seriously. They're vultures.

External validation: Not even kidding here--and maybe this is a sad reality--but getting published as quickly as possible, even as a minor author--is immensely helpful for buffering one's mental health. All it is is your name typed neatly into a PDF, but it's also a way to say "I was here. I did something. It's in PubMed now, so it's real."

Again, easier said than done. But it's something to consider if you're prone to impostor syndrome: what's the best path to publication? Do you have a plan?

If you're on a project that just isn't working (and hasn't been working for a long time), get another project with a more sure route to publication.

Have an exit strategy: This might be the biggest contributor to mental health issues in people I know. And I think it's part of why the average path to PhD, as was mentioned in the previous post, is over 6 years. There's no clear indicator of what's "good enough" to graduate. And maybe because of a combination of impostor syndrome, a loss of direction, and thinking "well, everyone takes 6 years", many people just wait until late in their career to look towards the next step.

I've seen several PIs whose philosophy is that when a student has secured their next position (postdoc, job, etc), he/she will facilitate their graduation as soon as possible. That seems like the best way to do it.

Not every group is like that, though--and hence many people spend their time in a morass of career uncertainty. If you're ever had a full bladder during a seminar with a particularly long-winded presenter, it's the same idea. It's not the pressure, but the temporal uncertainty of the ending that is most discomforting.

From my own personal experience, then, the biggest way to deal with the mental stress of grad school is this: decide what variables you can change and where exactly you are taking yourself. For me, this included pulling the plug on a high risk project, and more importantly, it also meant explicitly articulating an exit plan and reaching an understanding on this and my career goal with my PI.

And it was an immense relief.

Having a semi-defined end in sight and mind is invaluable (and something I've always envied of those in MBA, JD, DVM, or MD programs, even though those are more stressful in other ways).

The Grass Isn't Necessarily Greener

Chemjobber--looking back on what you said about stress in industry (and about the outside world not being a panacea for mental health tribulations) also highlights something that is unhealthy among those of us in grad school.

We tend to compare our situation to industry or to other fields (engineering, computer science, pharmacy, law). Usually that descends into "look at the benefits that X has", "look at the few hours that Y works", and "look how much Z gets paid".

I think what we ignore is how politics driven nearly every career, scientific or not, academic or not, is. We assume that academia is the worst, because we came into academia with illusions of its nobility and vision, and then the curtain was pulled back.

But my feeling is that the reality is this: it's rare, nowadays, for young professionals not to work extended hours. Maybe 80 hours a week isn't common, and maybe a lot of fields get more Saturdays. But my own parents worked Saturdays and 60+ hour weeks in their twenties--and they are in a business field. My feeling is that part of any professional's early career is learning how to maximize their productivity, deal with time management, and establish their value in the workforce. In grad school, we just do that for much less money.

That's not the view I had two years ago, admittedly--at the time, I thought 60 hours a week was almost inhumane. That's changed somewhat.

I write this as a large swath of the US is experiencing a spat of cold temperature (far below freezing, with high winds). I write it from an apartment that, even as a student, I can afford to keep heated, as I use a broadband internet collection to play music in the background. My tap water will not give me parasites. I will not likely be shot tomorrow--in fact, I might eat Chipotle. Some of the food in my fridge will likely expire before I can eat it, and that won't be a big deal for me, financially. I can put gas in my car and travel across several states to see family several times a year.

The point is this: I am very thankful for what I do have, even if I'm working more hours than I would ideally like to, and if I go in on Saturdays. There's a lot of problems with grad school--power imbalances, careerism, politics--but it's not as bad as we sometimes make it out to be. Dwelling on the negatives, rather than changing what you can and accepting what you can't, is detrimental to mental health.

Restated: the grass on the other side isn't necessarily as green as it looks, and the grass on this side isn't as brown.

Just Say "No" to Grad School

Despite the coping strategies that I have and that I've seen people use, grad school can be too much. And that's okay--everyone's got different expectations and life goals. It simply doesn't make sense to stay in grad school if it's all a downhill slump.

So that raises what I think is an important question (and one you, Chemjobber, mentioned in your post)--one that I think is worth wrapping up with. Actually, it's two questions:

How do you make a decision to leave or not leave grad school? and Should I go to grad school in the first place?

They're related.

I mentioned a second question--Should I go to grad school in the first place?  I'll consider that one first.

I don't think grad school is for everyone. I don't think grad school is for everyone smart, either. I don't think it's some pinnacle of achievement that puts PhD-holders on an intellectual plane above BS-holders. And I think going to grad school can be an incredibly unwise decision--and it shouldn't be undertaken lightly.

As the posts and comments in the last mental health dialogue made clear, grad school can be very mentally and emotionally taxing, And it is especially hard on those who are prone to burnout or mental health issues, which I suspect tend to be amplified in the academic environment (even in lower-hour groups). Be very sure.

There are lots of bad reasons for going to grad school: not knowing what else to do, ego, thinking it's the path for smart people, not wanting a boss, thinking it's a land of total freedom, wanting to be called "Dr" (PhDs are NOT "real" doctors, and real doctors think it's very adorable when they assume they are), thinking it will be the path to increased riches, etc.

There are good reasons to go to grad school, of course, but one needs to be exceptionally sure of these. It's half a decade--at least--until the end. That's a lot of opportunity cost--and lost salary. It's sacrificing your twenties on the altar of science.

As for the other question--How does one know when to quit? I've seen a lot of people who would be happier quitting grad school--but mostly, they don't. They don't out of pride, or inertia, or wanting the title, or being afraid of what others will think. Those aren't good reasons, but they are powerful ones. I've also seen people who think they would be happier quitting but are still driven for the job that the PhD will enable--it's probably worth it for them to stay in, due to the payoff in the long term.

There's a concept in business decision-making known as "sunk costs". Put plainly, sunk costs have been incurred and thus can't change. In rational economic thinking, you shouldn't consider sunk costs in a decision--they're in the past, and only future costs/benefits--those you can change--are relevant from an objective decision-making standpoint.

Behavioral economics suggests that people do--quite irrationally--weigh sunk costs. I had a community band director once who exemplified this. He paid quite a sum for a particular musical score. We hated it. He didn't care for it, either. But we played it every few months because he felt that he had "paid good money for it" and "didn't want it to go to waste."

The same is true of grad students. There's a pervasive thought--"I've already put in 2 years, so it would be a waste of time to quit now." (Or however many years). But time already invested is a sunk cost. It doesn't matter how much time you've put in if you're not going to get anything out of the degree.

Only three factors should matter when deciding whether to quit grad school:

  1. Am I happy right now? (Am I mentally healthy? Are there variables I can change about my current situation to make myself happier?)
  2. What is the future benefit of me getting this degree in comparison to not getting it? (is it necessary for your career? Is it limiting?) 
  3. What am I missing out on by following through with grad school? (This is known as "opportunity cost" and includes the salary you could collect at a different job, time spent with friends, family, and your SO, traveling while young and unencumbered, etc). 

If the answers to those aren't positive, there's no reason to stay.

Quitting grad school is a really taboo subject--maybe even more so than mental health or the fact that academia is pretty rubbish at drug discovery. Why don't we talk about it more? Grad school should not be the only priority in one's life--and it's perfectly OK for it not to be the highest priority (although certain PIs may disagree).

In the end, it shouldn't matter what colleagues think about whether one quits or not. What matters are the three questions above.

I asked myself these recently. I was highly stressed, had seen a project burn, and had thought deeply about my life priorities. I didn't see myself as a good scientist, but as someone who could be a mediocre-to-decent pharmacy tech pretending to be a scientist. I was ready to pack up and leave and to take my chances on another career. I had my quitting speech rehearsed and had started the motions. I had strongly implied to several people that this was a sure thing.

But I thought about it. I considered the factors above--thought about what I could change about my situation to make it work. I talked with some third parties both in and out of my desired career path. And I realized I needed the degree and the experience for what I wanted to do. I talked frankly with my PI, and he/she was supportive (surprisingly so) and understanding of my priorities and needs. And so I made the choice to stay on board, making the changes I needed to in order to be happy and productive.

I hope it was the right decision. Maybe in 2 more years we can revisit this topic again and see.

To wrap up: thanks, Chemjobber, for the opportunity to revisit this topic. I felt our last dialogue on this was valuable and appreciated the insight from the numerous scientists who weighed in. Thanks for your perspective, and I hope you stay well. 



Tuesday, January 6, 2015

Minty fresh terpenoids

With the holidays concluding (and stocks of candy canes dwindling) it's natural to ask: what's the difference between spearmint, peppermint, and wintergreen flavorings? 

Beyond the differences in their biological origin, various people have (not surprisingly) analyzed the constituents of the essential oils of each. 

Peppermint oil (Mentha × piperita L., a cross between watermint, Mentha aquatica, and spearmint, Mentha spicata) has seasonal and regional variation, but it is primarily a mixture of menthol (>30%) and menthone (>15%, sometimes >30%). Also present are a large diversity of additional compounds, including menthyl acetate, eucalyptol, limonene, beta-pinene, beta-caryophyllene, trans-carane, pulegone, (+)-carvone, and neomenthol. Some of these components (pulegone and menthofuran, for instance), are undesirable from flavor or toxicity standpoints, and have been the subject of metabolic engineering. A sampling:

Spearmint comes from the essential oil of Mentha spicata and differs markedly from peppermint oil mostly in the relatively low abundance of menthol (<1%); it's still a complex mixture. The primary flavor component in this case is R-carvone (>50-75%). Limonene is more prominent than in peppermint. Other components include eucalyptol, trans-carveol, dihydrocarveol, caryophyllene, beta-bourbonene, linalool, beta-pinene, and germacrene D. 

Wintergreen (essential oil commonly from Gaultheria procumbens) is arguably simpler than either peppermint or spearmint and has a greater variety of sources. The chief flavor component here is methyl salicylate (a whopping ~98%), although one also finds limonene, myrcene, cadinene, carene, and pinene (alpha-pinene, in contrast to the predominantly beta-pinene in peppermint/spearmint).

For a really nice graphic of chemical compounds as flavor components in herbs and spices in general, see this post at Compound Interest

All in all, terpenes are nice.

Wednesday, July 24, 2013

Sixteen Columns

Vittorio over at Labsolutely has a very clever and amusing post up re-imagining the X-Men as chemists.

So what other media genres share cross-over with our field?

The modern art form deemed the "chick flick" shares key features with tactics used to recruit students into graduate school in chemistry. Namely: (1) hopelessly romantic view of the content; (2) focus on idolizing the celebrities of the subfield (e.g. Tom Hanks, Phil Baran); and (3) careful shielding of the subject from reality of life/lab. And of course, both chick flicks and science place an emphasis on diaries.

In a salute to both, here are some chick flicks in the context of science:*

  1. How to Lose a Grant in 10 Days
  2. Unemployed Going on 30
  3. The Proposal
  4. Never Been Published
  5. 27 Postdocs
  6. What's Reproducibility Got to Do with It
  7. The Devil Wears PPE
  8. Sixteen Columns
  9. My Best Friend's Defense
  10. What PIs Want
  11. Save the Last Authorship
  12. Bridget Jones's Lab Notebook
  13. When Harry Met Sally at an ACS Regional Meeting
  14. The Lab Notebook
  15. Out of Academia
  16. Sleepless in Grant Season
  17. The English Postdoc
  18. Gloves Actually
  19. How Stella Got Her Glassware Back
  20. 10 Things I Hate About U...niversities
  21. Pride & PNAS
  22. Crazy, Stupid, Reaction Mechanisms
  23. Peggy Sue Got Funded
  24. P.S. I Love the Combiflash
  25. Flashcolumn

* Note: these are in no particular order; the author claims no expertship on relative merits of chick flicks.

Thursday, July 11, 2013

Why Steve Strauss should stop hiring English majors and hire some scientists instead

Recently, a few people I know shared this column on Facebook. Written by Steve Strauss, a lawyer/author and self-described "small business expert", the short piece from the Huffington Post makes the case that English majors are pretty much the bee's knees. Strauss prefers to hire English majors for a variety of roles, as he explains:
I love English majors. I love how smart they are. I love their intellectual curiosity. And I love their bold choice for a major. Most of all, I love to hire them. 
A recent article by the great David Brooks in the New York Times about the changing nature of the Humanities in higher education just reinforced why, when given my druthers, English majors are my employee of choice. 
And the reason is not that I am a writer; I more consider myself an entrepreneur than anything else. I run a small business and the people I hire do a variety of tasks -- SEO, project management, social media, and so forth. 
For my money (literally and figuratively), for my needs, and I suggest the needs of most small businesses, English majors are easily the top choice when it comes to getting the type of teammate who can make us all better, as they say in basketball.
Strauss goes on specify some key traits apparently endemic to the English major population. These are: (1) English majors are smart and creative independent thinkers, more so than business majors; (2) English majors are bolder risk-takers than others; (3) English majors are always better writers; and (4) English majors are easy to work with.

I suspect many scientists will disagree. I take issue with the broadness of Strauss's assertions--though he never claims to have broadly surveyed skillsets of humanities scholars, his descriptors read like mere feel-good fluff. Yes, there are English majors who have those characteristics, and many English majors are successful. But "rigor" and "difficult assignments" are not essential traits of the undergraduate English experience.  While English may allow deep thinking, it doesn't absolutely require it, and it's certainly easier to skate through an English degree than, say, one in chemical physics or organic chemistry.

You see more chemists who also know literature than you see literary analysts who know molecular orbital theory. But isn't that just because science is more specialized? Well, yes and no. Individual fields of science certainly have their own jargon, methodology, and bodies of knowledge. But the scientific process is fairly universal, and you see people switch fields in their BS/PhD and PhD/postdoc transitions.

That all sounds harsh, of course, and borders on the increasingly-prevalent-but-misguided attitude of "cut the humanities, boost only employable fields". So to clarify: I like the humanities. I really do. I've always enjoyed literature and music (both production and consumption), and I think their study is vital for making a person more culturally aware and well-rounded. I have opinions on writers and composers. I was one of those people who didn't whine about general-education requirements interfering with "real" coursework. But assigning top general employability status to English majors overlooks a key group of students who, when successful, possess all the abovementioned skills and more: science majors.

The case for hiring science majors

As previously mentioned, Strauss touted the creativity of English majors and their ability to think analytically. Creativity is essential to good science as well; skilled researchers tend to be creative people who see alternate ways to solve problems. Moreover, scientists find solutions that work, based on reality and reproducibility. This clarification is important, because "analysis" means very different things in scientific and non-scientific circles. However, scientists are quite good at two things: (1) finding information; and (2) evaluating information.

Strauss also claims English majors are superior risk-takers. But scientists are too. They have to be. Good research is always at the edge of knowledge--which means it might not work. Bench time might be wasted. A six-year PhD might produce no results and lead to no job. Ideas might get defunded and banished to obscurity. Going to grad school is a tremendous risk. So is working for an untenured professor, or starting a brand-new project. So the advantage here again goes to scientists. Additionally, scientific risk-taking is grounded in reality--helpful for businesses.

What other employable traits do scientists tend to have? Work ethic: long hours are the norm and determination over long periods of time (ca. 5 years) is required. Versatility: the scientific method is employable between variant research areas but also to management and business decisions. Technical skills: this probably goes without saying, but intimate knowledge of scientific theory and technique isn't easily gleaned from Google. Even in non-bench roles, this can be quite important. Teamwork: whereas writing English papers is a solitary venture, lab research is done in groups, and collaboration between students and labs on the experiment or project scale is commonplace. Objectivity: whereas the humanities stress the voice and identity of the individual (subjectivity), science emphasizes minimization of bias. This is useful in risk assessment, evaluation, project design, etc.

All in all, I think science majors sound pretty employable.

What we can learn from our English-wrangling colleagues

The claim about English majors being superior writers is also worth examining. Do English majors write? Yes. Do they write a lot? Most of them. Do they write well? The good ones write academic papers well, but an increased vocabulary and flowery verbiage doesn't mean good communication. Of course, many English majors are good communicators, but the degree doesn't guarantee that. And not having an English degree doesn't mean you can't write just as well as someone who has one.

It's worth noting that significant differences exist between scientific/technical and academic (non-scientific) writing. In another life, I worked closely with undergraduate writing tutors. Most were English majors, and as a lot they were very intelligent. But all of them were horrid at actually helping science students improve their communication skills. The result was a continuous stream of frustrated chemistry students with half-mangled lab reports. The writing process is fundamentally different across the humanities/science divide, which makes me skeptical that the garden-variety English major would be good at writing in a technical or scientific context (where content is highly specific, highly technical, and verbal economy is vital). Some are good at it, but it's not because of Chaucer.

That being said, scientists themselves are very commonly awful writers. Those who deny this or think it's not important are simply either ignorant or delusional. Then again, scientists are perhaps more likely to be blunt and direct, which has its appeal. Regardless, it's probably good for budding scientists to take all the writing experience they can get and to pay attention not only to the facts of what they write but the organization and presentation. Clear communication makes ideas easier to sell, cuts down on wasted time, and improves work efficiency. The ability to write well (more than just JACS communications) can be a huge selling-point when building an employment skillset, as it extends to grants, business proposals, technical reports, and intellectual property claims.

A final anecdote.

A friend of mine switched from pre-med to business during undergrad and found himself in a business database systems class. The class entailed a team-based project wherein each group of students needed to create a database system for a local business. Several of the born-and-bred business majors insisted that the class was probably the most difficult in the university. Having taken two years of pre-med coursework, my friend pointed out the difficulty and rigor in the hard sciences, especially in independent research. Oh, no way, the business majors insisted, scientific research is just following recipes.

The piece is short, so it's worth reading.  Do also peruse the comment section, which is rife with people praising Strauss's words and/or correcting each others' grammar/diction. 

Tuesday, June 25, 2013

Stop using that word: Accordance

Consider "accordance". It's a sleek, shiny word. But it's terribly misused in scientific manuscripts.

To pick on just one example, take the following text from a recent publication by Neil Kelleher's group at Northwestern (bold emphasis mine):
Our observations were in accordance with a previous study on nostocyclopeptide, where certain amino acids in the peptide sequence were found essential for the spontaneous macrocyclization of the peptidyl aldehyde intermediate into a cyclic imine.
And another example from a total synthesis of daptomycin by Xuechen Li:
The spectrum was in full accordance with those in the literature.
Not quite right.

"Accord" implies agreement. It's what writers usually mean when they use "accordance". For instance:
His dismal personal life was in accord with his excellent progress in total synthesis.
"Accordance", in contrast, implied obedience. It refers to compliance with a rule.
My one day of vacation per year is in accordance with group policy.
Examples of the correct use of "accordance" are actually hard to find. Consider this paper by Robert West at Wisconsin. An excerpt (bold emphasis mine):
In accordance with Bent’s rule, the increased R–O bond polarities of permethylated species lead to increased oxygen hybrid s-character and R–O–R bending angles in both ethers and siloxanes.
That one is arguably correct.

The difficulty is probably that "in accord with" doesn't flow quite smoothly. Perhaps a better option would be simply to say "in agreement with". Either way, reviewers probably won't catch it.

This has been a public service announcement.

Thursday, June 20, 2013

Carbenes: turns out, nature has them, too

Enzymes are like nature's little gloveboxes. It's really quite interesting what kind of chemistries are possible in aqueous, biological conditions just by manipulation of the local electronic and steric environment by the structure of enzymatic active sites.

Take carbenes. Everybody likes a carbene--it's a lone pair on carbon, but it's formally neutral, and it does interesting reactions like alkene insertion (cyclopropanation), C-H insertion, rearrangements, and the like.

One of the more interesting aspects of carbenes is their variable reactivity. They can exist in a singlet (depicted as lone-pair) or triplet (depicted as diradical) form. Depending on their electronic environment, they can react as nucleophiles (aided by a high-lying HOMO) or electrophiles (encouraged by lowering the LUMO). Their reactions can be stereospecific through concerted pathways (singlet carbenes) or non-stereospecific through stepwise mechanisms (triplet carbenes). All of this is tuned, not surprisingly, through the electronic/steric environment around the carbon in question.

Carbenes are typically highly reactive and short-lived, though examples of persistent carbenes are now well-known. N-heterocyclic carbenes (NHCs) make a prime example. The electron-rich di-adamantyl NHC shown above, for instance, was described in 1991 and can be crystallized (it melts, by the way, at 240 degrees Celsius).

Note the electronic nature of the carbene: the carbon is flanked by two nitrogens, each bearing lone pairs capable of donating electron density into the carbene's p orbital. This acts to stabilize the singlet state and imbues NHCs with admirable properties as metal ligands (electron rich sigma donors which bond quite strongly to metal centers) The most famous of these is probably Grubbs' second-generation catalyst, which bears an NHC in lieu of one of the phosphine ligands of the first-generation counterpart. Besides olefin metathesis, though, persistent carbenes (as NHCs) are quite useful ligands for tricky C-C cross-couplings. Specifically, the so-called Pd-PEPPSI complexes are useful for coupling of tetrahedral carbon centers to each other.

It turns out that nature utilizes carbenes as well. Take a look at vitamin B1--also known as thiamin. It's an essential coenzyme which, as it turns out, we can't make and must obtain in our diet. There's several forms consisting of various decorations, usually of the hydroxyl moiety. One of these is thiamin diphosphate (ThDP), which, if you didn't guess, is thiamin with diphosphate attached (it also goes by the name thiamin pyrophosphate, or TPP, which is definitely not confusing at all). ThDP is a coenzyme for pyruvate decarboxylate and pyruvate oxidase, among other enzymes.

If you look at thiamine, there's a place--right between that sulfur and its neighborly nitrogen--that seems like a nice candidate for a carbene. There's been a debate in the literature; that carbon must be deprotonated for catalytic activity, and it hasn't been clear whether the associated enzymatic reaction proceeds via a carbanion or the short-lived carbene. A recent report in Nature Chemical Biology provides evidence for the latter. The authors examined thiamin diphosphate with the enzyme pyruvate oxidase (from bacterial origins). Phosphate was employed as a mimic of the substrate (pyruvate) that would bind similarly but not form a covalent adduct--this was to see if substrate binding might correspond with the formation of a carbene.

Via circular dichroism (CD), and X-ray diffraction, the authors give evidence that although the coenzyme is C-protonated in its resting state, binding of phosphate results in accumulation of either the carbanion/carbene form. This is narrowed down to the carbene chiefly through analysis of the XRD structure. Not only was the electron density consistent, but the bond lengths and angles were similar to synthetic thiazolium carbenes previously reported. The authors mention similar results upon analysis of the ThDP/cyclohexane-1,2-dione hydrolase complex.

Essentially, under physiologically relevant equilibrium conditions, the thiamine/enzyme complex can accumulate a carbene. In water. That's quite cool.

Wednesday, May 22, 2013

Academic salaries: some numbers and graphs

The topic of academic salaries came up recently and I figured I'd look a little further. Where does chemistry stand? After all, jobs are scarce--how do academic positions pay compared to other disciplines?

Lots of resources exist for salary issues that are much more data-thorough, so take the following numbers with a grain of salt. For more in-depth info, a few resources include HigherEdJobs, The Chronicle of Higher Education, or a web search.

I took a (somewhat) random single institution (Bowling Green State University, Ohio) of medium size (ca. 15,000 undergraduates) that also offers graduate degrees (in chemistry, an M.S. in chemistry and a Ph.D in photochemical sciences are available). Ohio was chosen as an example state simply because of the ready availability of data.

Salary information (for a few years back) is available for all Ohio's higher ed institutions through the Buckeye Institute. I grabbed the 2010 info for the university and present below the averages for four standard academic ranks (lecturer/instructor, assistant professor, associate professor, and full professor) across 14 broad but somewhat arbitrarily chosen disciplines. Standard deviations aren't included and sample sizes were small in some cases, so caveat emptor and all that. (NB: click any chart for a larger view)

First, a graph of the disciplines ranked by associate professor salaries. It's quite interesting to me that chemistry is near the top--ahead of biology but also physics and geology. Moreover, associate professor salaries in chemistry rank a little short of computer science (by about $7,000) but above economics (by about $8,000). As would probably be expected, two business disciplines (management and accounting/M&IS) are way ahead. I don't know if that's endemic to the particular school or a general trend. Regardless (and probably again to no one's surprise), it looks like chemistry and the other sciences are pretty far ahead of the humanities by as much as business-related fields are ahead of science.

Ranking by full professor puts chemistry more in the middle of the pack:

Quite interestingly, though, are the salaries for assistant professor positions (typically the first 3-6 years of an academic appointment). Here the distribution is almost bimodal, with chemistry falling in a group ranging from  about $50,000 to $66,000. Then there's a $24,000 jump to the business disciplines and computer science, which compensate assistant professors on average from $89,000 up to a whopping $119,000! (For the math-challenged organic chemists, that's about double the chemistry salary for the first five years).

Why the giant divide? Market demand certainly plays a large role. Folks with graduate-level business and computer science skills are very, very employable, and generally aren't in markets plagued by the oversupply that science (and especially the humanities) face.

Lastly, check out the ranked salaries for instructors/lecturers. These are the teaching-only positions; for some disciplines this doesn't require a PhD. (For chemistry, I've seen very few lecturers without PhDs; many have postdoc or industrial experience).

Management here has the highest salary by far, but that's incidentally an n = 1 type scenario (there's only one lecturer in the management department, and they appear have an 'executive' position). Here the business gap disappears; average salaries range from $38,000 to $52,000. Interestingly, computer science ranks in at $61,000, which is probably indicative of its very high employability--you have to pay someone a lot to draw them away from an attractive industry job.

For fans of seeing-it-all, here's a ranked-by-associate graph including all four ranks.

Lastly, here's the average salaries for most of the public university chemistry departments in that particular state (Ohio) [note--data was not easily harvestable for Ohio University, Shawnee State, Central State, or Youngstown State].

This itself is somewhat interesting, as there's a wide distribution (assistant ranges from an average of $55,000 to $78,000; associate from $70,000 to $97,000; full professor from $101,000 to $131,000). Moreover, salary averages don't appear to correlate to institutional prestige (cf. Ohio State and University of Akron, for instance) nor to cost-of-living.

The ordering of schools even changes by faculty rank--Cleveland State tops out the assistant professor category, but Bowling Green wins for associate professor and University of Toledo for full professor. The only consistent element, it seems, is that Kent State pays the lowest for chemistry professors, across the board, of all the state schools shown.

Again, take all this data with a grain of salt; I just think it's interesting stuff.