WWWTP? Epigenetics Edition

Dan Hurley's piece in Discover's May 2013 issue really fascinated me. Covering the mouse research of Profs. Meany and Szyf, Hurley explained how tragic events in ancestral lifetimes are passed down to offspring via DNA methylation, altering gene expression for generations.

As my chemist's eyes flitted across the page, I smiled at some familiar friends on p. 51 - line structures of nucleotide base cytosine. Just one* a few small problem(s)...did you catch them???

Source: Discover 5.2013

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See that nitrogen at the bottom? In the language of my sophomore organic professor, it's "very unhappy" that way. Nitrogen usually gets three bonds and a lone pair of electrons; I won't over-critique the missing dots, but there needs to be one of three things on that structure:

1. A generic R-group (meaning a new carbon chain)

2. A proton (indicating the free cytosine base)

3. A "minus" sign (indicating an anion)

Kudos to the graphic artist, though, who actually used standard chemical notation here. Many general science mags would have just used a colored-in hexagon.

*Update, 6/17/13 - As commenters have piled on, we note the empty valences on the two aromatic carbons (carbanions?), as well as questions over whether a methyl group counts as a "compound."

What's Important? Data Analysis

Thanks again to everyone who wrote in with their two (or three) most important job criteria.

We had a final tally of 42 (!) respondents, who gave a total of 94 answers. Here's the much-vaunted pie chart I promised on Friday:

Comments:

1. Many people wanted "meaning" behind their daily work. There're a lot of terms one could use to describe that special feeling of fulfillment - they're all included in the largest pie wedge.

2. Only a tenth of you indicated salary or benefits as part of your criteria. Two percent mentioned promotions or advancement. Shocking, really, especially in a down economy.

3. The "Misc" category included responses such as autonomy, lack of bureaucracy, morality, health, and...free food.

4. Prediction: If I offered a 5-year job working on cures for neglected diseases, starring top-flight, team-oriented colleagues located 10 minutes down the street from your house, most of you would take it.

Right?

So, in the end, have we vindicated Mr. Sturgeon's beliefs about modern science workers? I believe we have. Interesting work and collegiality really do seem to matter most!*

*Limitations: Now, this only surveyed 42 chemists, so I'm missing out on the other 90,858. I'm well aware that the survey only caught 1) chemists reading blogs, 2) chemists on Twitter, and 3) chemists who could comment on blogs during (presumably) working hours. Not exactly perfect conditions for such a study. My 'analysis,' such as it was, had no tests for accuracy, and no way to filter out trolls. C'est la vie.

Challenge: I'd love to see this survey writ large...wouldn't you? Perhaps a larger journal or scientific society could issue the survey to their members (lookin' at you, ACS, Science...).

Readers: Questions, comments? Feel free to contact me (Seearroh_AT_gmail).

What's Important to YOU?

Yesterday's post over at Chemjobber's place really caught my attention. Paul Sturgeon, writing in trade mag Plastics News, opined that employers don't attract top talent due to fundamental misunderstandings in what "next-gen" employees really care about.

Made me wonder, if you asked some current science professionals about their top two workplace criteria, what would you get? Would Mr. Sturgeon be dismissed, or vindicated?

OK, readers, here's the game: Please list your top two workplace criteria in the Comments section. Once I get ~10 entries, I'll start to input them in a super-sciencey gizmo called a pie chart. Hopefully, we'll get a few more entrants, and I can start to pin down what's important (and what's really not).

I'll go first: My top two criteria are 1. interesting / meaningful work, and 2. length of commute.

Can't wait to see your responses!

(N.B. Certainly, a wide demographic visits chem blogs, but I'd argue the results will skew towards slightly younger, highly-educated, potentially job-seeking professionals. Exactly the demographic the above article argues companies wish to hire!)

Friday Fun: Thulium Breaks 'Em Down

Seriously, how often do you see thulium in the chemistry mainstream?

Prof. David Procter and Dr. Michael Szostak, of U. Manchester in England, want you to think of it a lot more often. Their latest ACIEE explores some crazy stunts thulium diiodide can do when mixed with a little alcohol: Blowing apart esters. Reducing arenes. Unwrapping amides (see below):

All thanks to the extra reducing power of this "non-classical" lanthanide salt. At a good 50% more than samarium diiodide, thulium diiodide can inject a single electron into just about any C=O or arene around, and there's evidence that it slips into neighboring C-N bonds to promote fragmentation:

Source: Szostak, ACIEE 2013

Bill Evans (organometallics, not jazz) previously explored this reagent over a decade ago, marketing it as a souped-up SmI2 / HMPA. His study looked at cyclic ketones, which formed adducts with primary iodides in less than a minute with a healthy dose of TmI2(DME). Despite these exciting early results, it appears that thulium took a back burner to the samarium 'craze' of the mid-'00s, and only now gets its chance in the limelight.

Keep an eye out for more TmI2 reactions; after 100 years of new bond-forming reactions, it's nice to see trends to the contrary.

Happy Friday,
SAO

Update (6/14/13) - Added Prof. Procter and group website. 
(6/14/13) - Changed lactam to amide - thanks, Anon!

BuLi: Not Just a Base Anymore

When do you reach for that bottle of n-butyllithium at the back of the fridge? Making anions, sure, but BuLi's also great at ripping off halogens, destroying esters, alkylating imines, or swapping lithium for other metals (see: Sn, Zn, B, Cu, etc...).

What about using BuLi as an off-the-shelf cross-coupling partner? Sure, sounds like a methyl-ethyl-butyl-futile joke gone too far, but there're quite a few of those aryllithiums in catalogs nowadays...

Looks like Ben Feringa's got you covered. In Nature Chemistry, his group reveals that slow addition of a diluted organolithium to an aryl or vinyl bromide mixed with some electron-rich Pd(0) precatalysts provides alkylated products with high selectivity. At room temp. In one hour. In the presence of chlorides, esters, free alcohols, and all sorts of things that usually gum up the works. Zoinks!

I'll admit it - As someone who's spent a decent part of my life trying to glom one carbon onto another (grumbling while I purified yet another organotin or boronate), these initial results look promising. I'm sure they're furiously working on the alkyl-alkyl (sp3) coupling as we speak - good luck, that one's gonna be a lot harder.

P.S. Kudos for a well-thought-out Supporting Info section, too. The authors discuss their optimization process almost "stream-of-consciousness"-like, letting you vicariously learn the chemistry along with them.

Killer Schwag from ACS

I feel like I've seen a snow leopard, a yeti, a dodo bird, Bigfoot, and a giant squid simultaneously.

This piece de resistance arrived by first-class mail today. Behold, the elusive ACS Five Year Mug:

Oh. My. Gosh. 

I am grateful to whomever at ACS / C&EN heard my griping a few weeks ago:

@apgoldst -In that case, I'm holding out for my "Mugnesium" next year #snerk @chemjobber
— See Arr Oh (@SeeArrOh) May 21, 2013

Kudos to ACS for quickly addressing the situation. Now, about those next 8 elements...*

*Seriously, ACS, I would be most willing to build a periodic table of mugs. I promise to stay alive / renew membership at least long enough to get to the transition metals. For an extra goof, you could send me a "tin cup" on my 50th Anniversary (Sn). 

Pyramid Power!

Atop the energy barrier between hardcore synthetic jocks and dyed-in-the-wool physical chemists lives a dedicated group: the molecular architects. A craving for perfect Platonic shapes, combined with the need to push the limits of bond and orbital theory, drive them towards projects like bullvalenes, cubane, or buckyballs. Despite the obvious challenges - bullvalenes shift and change, cubanes feel some strain - the structures' aesthetic appeal keeps us coming back for more.

Well, another class of shapely compounds seems poised to fall. Enter Pyramidanes*:

Source: JACS | Lee, Sekiguchi

Reported a few days back in JACS by a collaboration between Japanese, French, and Russian scientists, the  near-tetrahedral compounds are within shouting distance of an all-carbon version, never synthesized by human hands. I gotta say, they look pretty awesome. Just staring at it brings up so many questions: what's the hybridization of that top atom? How much strain energy? Could you make some schnazzy ligands from it? How labile is that Sn, anyway? Does this thing blow apart in TBAF?

The crew provides an in-depth discussion of frontier MO theory**, bond orders (fractional all around,
from 0.4-0.7), and NMR properties, concluding that there's a decent structural contribution from the ionic resonance form (see below).

The authors even suggest that the "cyclobutadiene" moiety - the pyramid "base" - can be stuck onto other metals; stable pyramidanes might work as strained-ring storage capsules.

Now I'm excited for the all-carbon version, which (theory predicts) has a lone pair at the apex...crazy!
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*For the absurdly technical or IUPAC-minded, the authors offer alternative names such as tetracyclo-[2.1.0.0.0] pentane, or (my favorite) [3.3.3.3]fenestrane

**N.B. I'm no p-chemist, so someone else can go through the nitty-gritty there...