Monday, September 22, 2014

Honing Halophilicity

Let's say you have a late-stage drug candidate, with an alcohol, an olefin, and a pyridine. Now you toss in one equivalent of a chlorinating reagent.

Which functional group gets halogenated first?

Babak Borhan and colleagues from Michigan State and Dow may have your answer. In a recent JACS full article, they disclose the HalA (halenium affinity) scale, a DFT-calculated delta to describe the relative reactivity of various groups to an incoming halogen source. They back up their calculations with NMR competition studies, showing, for example, that two structurally similar molecules have a rather skewed 7:1 equilibrium, as predicted by a 1.1 kcal / mol difference in HalA:

Borhan et. al., JACS 2014
Using 500 computationally-evaluated functional chlorenium "acceptors" (Lewis bases), Borhan and colleagues create a chart to help answer our initial question: What reacts first?

I'm certain even more detailed versions of this chart are currently underway. I wonder how well it would extend to prediction of methyl or trifluoromethyl group additions?

WWWTP - Lab Signs Edition

From the Sept 2014 issue of Wired magazine:

I understand that magazines require flashy, highly-posed photographs to move copy.
That said, did no one in the Editor's office notice all the warnings on that hood sash?
They read:

"Wear proper PPE (Goggles, Gloves, Protective Clothing)"
"Always properly label your chemicals, including your initials. Any unknowns will be disposed of as Hazardous Waste"

As far as I can tell, the researcher pictured is in violation of all three signs. Ye Gods.

WWWTP? SciAm Epigenetics Edition

From the August 2014 issue of Scientific American:

This illustration hurts on a few levels. "Methyl" and "Acetyl" are functional groups - common clusters of atoms that appear in larger molecules - not themselves chemicals, per se. If the methyl were actually represented by this red ball, it wouldn't be quite so large (it's only four atoms), nor would it be attached at the outside of the sugar backbone (it's on the nucleobases themselves).

Did no one see last year's Discover infographic? At least SciAm's gets the helix right!

Readers - Anyone know who fact-checks scientific illustrations?

Wednesday, September 10, 2014

Bill Gates' Chem Secret

*Update - I see CJ beat me to it!

Buried deep within a recent NY Times Magazine article, a humbling reminder that not all knowledge comes easily to billionaire tech scions:
source: Microsoft
"Without prompting, [Bill Gates] recounted getting a bad grade in an eighth-grade geography course (“They paired me up with a moron, and I realized these people thought I was stupid, and it really pissed me off!”) and the only C-plus he ever received, in organic chemistry, at Harvard (“I’m pretty sure. I’d have to double-check my transcript. I think I never ever got a B ever at Harvard. I got a C-plus, and I got A’s!”)."
I can't help but draw a connecting line to one of my fictional heroes, as ChemBark noted.

O-Chem is hard. I guess I'm lucky it made sense to me.

Monday, September 1, 2014

Resistant Dialogue

Street garden flowers, likely Allium sp.
Overheard at a '50s-style diner, in Big City, USA, between two waiters:

"I've been feeling really stuffy and sick lately"
"Well, you know what I do? I just get a Z-pak"
"Does it work?"
"Oh yeah. You only take 6 pills, and you feel great in a few days. Though, sometimes I end up taking two packs"

And that, dear readers, explains some of the nagging reasons we now have azithromycin-resistant bacteria.

To those in the U.S. - Happy Labor Day
To those in the rest of the world - Happy Monday*

*Inspired by a classic Chemjobber bit.

Sunday, August 3, 2014

C'mon, Let's Twist Again, Like We Did (This) Summer

Dirk Trauner: natural products chemist, vision researcher, neuropharmacologist,
. . . carbon nano-tube enthusiast?

Apparently, it's "crazy saturated hydrocarbons" month here at JLC. An astute observer clued me in to the Trauner group's latest pursuit - polytwistane. Studied for five decades by organic chemistry pioneers such as Whitlock, Deslongchamps, Oka, and von Rague Schleyer, twistanes have been tricky to coax into existence, owing to their propensity to rearrange into more stable adamantane.

In a 'gedanken' (thought) experiment, Allen, Schreiner, and Trauner mentally "add" bridging ethane units to twistane, stretching it out into a pseudo-helical oligomer (Chem. Eur. J.):

Chem. Eur. J. 2014, 1638.

Some fascinating molecular motifs fall out of their modeling studies. For example, unlike adamantane, polytwistane has three distinctly different C-C bond lengths, a factor chalked up to strain energy. However, it's in no danger of falling apart - the researchers calculate a "very modest" strain energy (~1.6 kcal / mol CH). All the hydrogens occupy positions on the outside (convex) surface of the tube. Finally, note that polytwistane is formally a polymerized version of acetylene, which we'll come back to later.

Emboldened by these in silico  results, Trauner and team take to synthesizing a basic unit of polytwistane, so-called "tritwistane" (Org. Biomol. Chem.). Starting from laticyclic polyenes -- think bicyclo[2.2.2]octene, connected end-to-end -- the researchers try a variety of electrophilic conditions to form the bond in question. Eventually, a combination of bromination / radical reduction produces the simple tritwistane oligomer:
Org. Biomol. Chem., 2014, 108.

At the close of this paper, Trauner deadpans that "attempts to synthesize polytwistane . . .from acetylene itself are ongoing in our laboratory..." Sounds like a tough nut to crack, but if he succeeds, he and his collaborators will have access to a rather rigid, narrow, twisted new material certain to possess interesting properties.

*Don't know the song in the title? Say hello to Chubby Checker!

Help Wanted: "Working Hours" Survey

Ofer Kedem, a postdoctoral researcher in the Weiss lab at Northwestern, has posted a survey to try and get a handle on the daily grind for academic chemists. He and his colleagues hope to garner enough data to publish their results in an open-source journal.

In the interest of statistical significance, won't you help them out?