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"

"NO STORAGE"

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?

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.

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.