Catching Copper's Ghosts

Copper, copper, everywhere (and much more than you'd think). It's found in coins, wiring, statues, paints, and even as part of a balanced diet. Chemists, in particular, have long loved copper for its ready availability, well-defined redox states, and its wealth of reactions; just last week, Prof. Sherry Chemler (SUNY-Buffalo) recounted nearly 100 years of copper's catalytic successes* in a Science perspective.

Source: Ogle / Bertz group | Angew. Chem.

Though scientists have long studied copper-catalyzed reaction, several short-lived, unstable intermediates
have defied characterization. Now, Profs. Craig Ogle and Steven Bertz (UNC-Charlotte) may have caught one of these ghosts: an elusive C=O copper pi complex. Using rapid-injection techniques at -100 degrees C, the team "freezes out" the complex, which they study by 2D NMR (which shows relative positions of various atoms) and cryoloop X-ray crystallography (shows absolute position in a fixed crystal lattice).

When the team warms the compound much above -10 degrees C, it immediately falls apart.

Isolating otherwise reactive intermediates lets us peer inside** the "black box" of catalysis. In this structure, the lithium atom tugs at the oxygen's lone pair, allowing the copper to slip into pi-coordination in a "side-on" fashion. Though it's tough to see from this picture (left), the authors point out that five atoms (O, C, Cu, Me-a, Me-b) all sit together in one plane, which validates earlier NMR models. Finally, there's some hints of reactive fate here, as the "bottom" methyl group shortens up, preparing to jump off the copper atom and onto the central carbon, while at the same time, the copper atom cozies up to the oxygen. Remarkable stuff.

* And that was just on one class of reactions!
**The deeper we look, the more crazy, head-scratching stuff we find. Ask your local organometallic enthusiast for more info...

Tracking Reactions? AFM FTW

Thanks to @slugnads at Wired for pointing out this story!
Update 5/31/13 - Derek's also got a great review going at Pipeline.

Remember 2009, when you gasped for a moment at the beautiful IBM structure of pentacene? 

Credit: BBC News | IBM | Science

In 2012, just in time for the 2012 London Olympics, the same team helped to image "olympicene."

Credit: BBC | IBM

And now, just 5 months into 2013, a team of researchers from UC-Berkeley / LBNL and several physics institutes in Spain have watched cyclizations occur on silver surfaces, using AFM tips to detect the ghostly products in stunning resolution:

Credit: Science | LBNL | UC-Berkeley | Wired

HOLY. COW.

As if this couldn't sound any more amazing, the researchers were able to predict and visualize several products previously predicted by theory, but never directly observed (stabilized diradicals, anyone?). 

So, will this be a standard technique for the practicing chemist? I'm guessing not for quite a few years, since the hardware involved still isn't commonplace, and the technique probably works best at prohibitively high dilutions with flat molecules. Med chem? Sure, you could watch a Suzuki coupling occur, or watch a Cope rearrangement, but for "3D" molecules (read: alkaloids, vitamins, sugars, etc...) I think NMR and X-ray crystallography will still be your best bets. 

But to paraphrase the futurists, predictions ironically suffer from poor foresight - after all, just over a month ago, a Japanese group disclosed how to take on-demand crystal structures of just about anything. So, I'm sure someone will invent a "rugged" surface capable of guiding the AFM tip around points and curves to monitor, say, real-time Pictet-Spengler reactions. Can't wait!

Precious Serendipity

Serendipity often drives scientific inquiry.

Ask a famous scientist - Feynman, Archimedes, Fleming, to name a few beneficiaries - they'd tell you it's better to be lucky than good. But Pasteur's paraphrased "Fortune favors the prepared mind" spells things out more clearly; diving into the nitty-gritty of chemical transformations often brings up a chance pearl of wisdom.

Such is the case for a recent JACS ASAP, out of the Wang group at Xiamen University in China. Let's set the stage: the scientists attempt to create a stabilized bimetallic cluster compound from gold, silver, and hemilabile P-N ligands. When the starting Ag-Au complex meets acetonitrile and methanol, something interesting occurs: a dimeric crystalline compound forms, bridged by two fully deprotonated acetonitriles!

Those golden pyramids are pretty schnazzy.
Source: JACS | Wang group

So, why am I so excited?

1. That's a CCN (3-) anion stuck in there! What if you could, say, build a tetra-substituted carbon center just by adding electrophiles in sequence?

2. C-H activation of sp3 bonds = hard. Especially at room temp.
Well, there's (technically) 6 sp3 C-H bonds missing in that complex!

3. The authors note that water forms as the reaction progresses. Most nitriles, in the presence of Au/Ag catalysts and water, will hydrate to form amides. Not so here.

4. The authors point out that a gold oxo intermediate must be present for the cluster to form. They also point out that similar gold oxo catalysts (and silver oxide bases) pop up in the literature. Perhaps crazy intermediates like this commonly arise in gold-catalyzed reactions?

The best part? Studies like this always leave you with more questions than answers.
Perfect fodder for future projects.

Pictures of the Month - Turbines and Beams

I don't know what it is about late March. Spring has sprung, flowers are blooming, grass growing green...and researchers are releasing killer images and wild papers at breakneck speed. This week, two images really caught my eye - a heart turbine, and a molecular beam generator. 

Artificial dual-turbine heart | Credit: New Scientist / Jeremiah Zagar

First up, a still from the short film Heart Stop Beating, shown courtesy of New Scientist TV. You're not imagining things - that's a dual-turbine pump, in a man's chest cavity! What's more, the man in question, Craig Lewis, lived for 5 weeks with this device in his chest, apparently no worse for wear, and died of an unrelated condition. 


In a Popular Science article from last month, one of the doctors behind the tech, Billy Cohn, described the materials used to construct the heart turbine:

"The materials needed to be blood-friendly. The structure needed to be resilient to deformation. It had to be formable in a limited space. We needed to be able to sew it, but the needle holes couldn’t let blood leak. And we had to be able to customize it in the OR by cutting it. I bought some ordinary Dacron from the fabric store and RTV silicone from Home Depot to impregnate the outside. I did all this in my garage."

Here's my question: What other materials could we construct replacement hearts out of? Perusing the stent literature, it seems like medical device makers try two different tactics: either a non-allergenic metal alloy, like nitinol (Ni-Ti) or cobalt chromium; or a biodegradable polymer, like a polyamide or poly-lactic acid (PLA). I'm hoping one of my materials-leaning readers could help me work through this in the comments.

Bumper Sticker: "My other car is a Molecular Beam Generator"
Credit: G. Meijer, Chem. Rev.

Next, in keeping with the "unbelievable machines" motif, here's the abstract picture for a recent Chem. Rev. on molecular beam generation. I'll admit, I'm not a physical chemist, but I would offer to learn if I got to play with a device like this! 


Molecular beams are formed, in the words of Prof. Gerard Meijer (Fritz Haber Institute | Max Planck), through a "controlled leak" from a pressurized cavity into a vacuum. Electromagnetic fields can be used to "shape" the beam, which chemists direct at targets, or smash into another beam to simulate basic binding events. My second question: What else could we do with these beams? Brief explorations into physics texts mention roles in quantum dots and nanocrystals, but I'd like to learn more. Readers?