The Chemistry Carnival Is Now Closed
Sep27

The Chemistry Carnival Is Now Closed

A quick update to thank all of you who participated in CENtral Science's first blog carnival. So far, I've tallied at least 20 entries! David and I will work to get a roundup post together in the next couple of days. And stay tuned to see which ones will be published in an upcoming issue of C&EN (that will take a little longer to figure...

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My Favorite Reaction’s Not A Reaction
Sep26

My Favorite Reaction’s Not A Reaction

As 7-Up was once called the “Un-Cola,” I am going to call my favorite reaction for CENtral Science’s Chemistry Blog Carnival the “Un-reaction.” When I was a graduate student and then postdoc, I wasn’t a synthesizer of things—I was a studier of molecular interactions: drugs sticking to DNA, proteins sticking to surfaces, lipids assembling into cell membrane mimics.   Some in the field might think this makes me an “un-chemist,” but I was indeed trained as a legitimate one. I was a physical chemist, which means that I still have books on my shelf with fun titles such as “Introduction to Electrodynamics,” “Symmetry and Spectroscopy,” and “Lasers in Chemistry.” It also means that I spent a lot of time in the dark and used physics-based tools in my work. Lasers, for instance. Spectroscopists in particular couldn’t survive without ‘em. My favorite laser would have to be the “HeNe” (pronounced hee-nee). That’s “helium neon” to all you synthesizers of compounds out there. In the lab, HeNe lasers are indispensible for their ability to help spectroscopists align optical tables. For instance, when you’re working with a high-repetition Nd:YAG laser, which puts out not-visible-to-the-naked-eye near-infrared light that can burn things (hair, especially, if you don’t tie it up in a ponytail while leaning over the optics), you want a visible, non-dangerous stand-in to put all the mirrors and lenses you’re using in place. Only then can you safely send the high-powered beam bouncing along down the optical pathway toward your sample. HeNe lasers are great stand-ins. And they work by electronic excitation and collisional energy transfer. That might not be a reaction in the purest sense of making and breaking bonds, but you’ll have to forgive this un-chemist for bending the rules of the Carnival a little bit. The first HeNe ever constructed was also the first available commercially—in 1962. It was then, and is still, composed of a small glass tube filled with, you guessed it, helium and neon atoms. An electrical discharge excites the electrons of the low-pressure helium atoms, which then collide with the neon atoms and their electrons, passing along the “excitement.” This energy transfer is possible because helium’s excited state is close in energy to neon’s. Excited-state neon atoms accumulate, creating what’s called a population inversion, and eventually, with nowhere left to go but down, they emit light and drop to an intermediate energy level before bumping up against the tube walls, releasing further energy in collision and reaching ground state. The burst of light the neon atoms emit is a red shade—632.8 nm—based on the difference in energy levels of their excited and intermediate states. Other...

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Amides: Humble But Useful
Sep15

Amides: Humble But Useful

A heartfelt thank-you to Chemjobber and See Arr Oh for helpful discussions! CENtral Science’s benevolent overlord, Rachel Pepling, has organized a blog carnival around the theme of "your favorite chemical reaction". For the Haystack's contribution, I thought it would be appropriate to write about a reaction medicinal chemists might find familiar. So I re-read See Arr Oh's post about which types of reactions were really the most common in the med-chem toolkit. I decided on amide formation, which sits just about at the top of the list. I’m not sure it’s my favorite chemical reaction; I’ve got a special place in my heart for the Heck reaction (or Mizoroki-Heck reaction), though I’ve already blogged extensively about it. But every amide bond formation I ran in grad school worked. That’s justification enough for me! Amides are the chemical ties that bind amino acids together to form peptides and proteins. Amides also turn up in a variety of other small molecules that nature makes. So it's not surprising that amides are frequently found in drugs. Take a look at University of Arizona chemist Jón T. Njarðarson's poster of top brand name drugs and marvel at the amide-y goodness. Amide bond formation isn't accomplished by a single, archetypical chemical reaction-- far from it. I thought I'd provide a brief overview of some classic chemistry in this area and then move into a selection of modern-day additions to the amide-construction toolkit. At first glance, it looks like all that’s needed to make an amide is to combine a carboxylic acid and an amine. But to make those two components come together, chemists have had to grease the wheels a bit by activating the carboxylic acid. Converting the carboxylic acid into an acid chloride or acid anhydride are among the oldest of the old-school methods for this. In 1955, MIT chemist John C. Sheehan reported a different idea—use of a coupling reagent, dicyclohexylcarbodiimide (DCC). Classics in Total Synthesis notes that in its time, DCC was "an important advance in the state of the art for forming amide bonds." In fact, Sheehan used it, along with the base potassium hydroxide, in the critical final step of the first total synthesis of penicillin-- construction of the beta-lactam ring of the molecule. However, separation of byproducts from the desired amide can be a limitation of DCC, according to the Haystack's intrepid guest blogger See Arr Oh. Today, "O-chemists have newer, sexier reagents," See Arr Oh adds. Those reagents include N-Ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDAC), a next-generation version of DCC that's water soluble, and other classes of activating reagents including uronium and phosphonium reagents. John Pokorsi, a student in Karl...

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