Cutting-Edge, Nobel-Worthy Chemistry

After all the early fuss about the merits of the 2012 Chemistry Nobel Prize, I noticed this challenge, couched in an earlier Chemjobber comment thread:

"The organic chemists seem to get their hides chapped most easily when a Nobel gets awarded to a 'biologist'. It's worth asking 'what are the fundamental unanswered questions in organic chemistry?'" (Emphasis mine)

Here are three areas, broadly defined, that I believe could win the Chemistry prize next year.

Synthetic trachea
University College London, 2011

1. Whither Polymers?  Darlings of early 20th-century industry, yet they've taken a back burner lately, winning their most recent Nobel in 2000. But, what a decade! Self-healing polymers. Fluoroelastomers you can print into any shape. Synthetic organs, even, grown from biodegradable polymer scaffolds. Trouble with this prize? Picking only three winners...

2. Biochemical Assembly Lines. Yes, cue the "it's not chemistry!" complaints, but I really like work which elucidates the cellular mechanisms plants, animals, and microbes use to assemble huge, medicinally-relevant natural products. Researchers can prompt E. coli to make an antifungal compound, for instance, or yeast to make a cancer therapy. Directed evolution of these assembly proteins, or the DNA which encodes them, can lead to products with wild substitutions and unexpected properties.  Bonus: All the 'big wheels' tend to be card-carrying chemists, and work in chemistry departments. The overarching goal tends to be chemical - utilization of Nature's machinery to produce new compounds.

Usual suspects: Christopher Walsh, Chaitan Khosla, David Liu, Ben Shen.

Walsh Group, JACS 2012

3. Fundamental Catalysis. Technically, there have been a few Nobels for this fairly recently (2001, 2005, 2011). But, what a decade! Here's some currently-exploding fields:

Organocatalysis
Chiral Anion Catalysis
Gold Catalysis
New carbene ligands
Frustrated Lewis pairs
Catalytic C-H activation

Any discipline on this short list could take home a Nobel within 10 years. Admittedly, some of these are rather young, but, as Ash has pointed out, the committee has rewarded ever-shorter publication-to-prize gaps, so it's not without precedent.

Usual Suspects: Dean Toste, Melanie Sanford, Anthony Arduengo, Graham Hutchings, Douglas Stephan, David MacMillan, Benjamin List

Readers, who would you award a Chemistry Nobel?

Chemistry Bumper Cars - Bertrand Edition

A little birdie has written to tell me of another fairly high-profile move - Prof. Guy Bertrand, formerly of UC-Riverside, seems to have moved to UC-San Diego* as early as June 2012.

Not familiar? His research covers main group complexes of phosphorus and boron, metathesis, gold catalysis, and some really neat takes on the N-heterocyclic carbene ligand framework (P.S. It certainly doesn't hurt when you're averaging a Science paper every other year!)

No word on whether the move was precipitated in order to fill a "Nicolaou-sized" hole in the UCSD faculty...

Congrats, Prof. Bertrand! We'll add you to the new map next year.

*I may be the only one entertained by this, but Prof. Bertrand is listed in the UC-San Diego "new faculty" page as "Professor, Above Scale (Distinguished)." Which begs the question, UCSD - show me that scale!

Redox Champ: NHC Ipso, Facto

Bond density difference between electron-rich and -poor NHCs
Source: Cavallo, JACS  ASAP

On the surface, N-heterocyclic carbenes (NHCs) seem like dream ligands. They have strong, neutral dative electron pairs, steric bulk, and enough variants now exist that chemists can "dial in" chirality, control R-group rotation, or add them as salts.
Could we possibly improve them any further?

A new JACS ASAP answers: of course! Professor Luigi Cavallo, and KAUST / U. de Salerno coworkers, like to examine NHC ligands computationally. Using Gaussian '09 molecular modeling software, the authors toss in a variety of electron-donating (ex: NMe2, Me) or withdrawing (ex: Br, NO2) substituents on the aryl rings of mock NHC ligands. They then virtually "staple" them onto Grubbs, Grela, and Ir-COD catalysts, and calculate the redox potentials of the Ru and Ir metal centers.

These data trend like you might expect: electron-withdrawing groups on the NHC increase the redox potential, while donating groups reduce it. Well, what's driving these effects? The authors initially suspect σ/π donicity (that's a $5.00 word, right there), the ability of the NHC-M bond to directly influence metal properties. However, they note something odd: there's precious little change in the bond lengths between complexes, only 0.005-0.05Å; by contrast, in carbon-carbon bonding, moving from alkane to alkene shaves off 0.2Å! Thus, they suspect that the NHCs' influence isn't coming through their main bond.

Well, if it's not electronics, then what's changing these redox properties? Enter the 'ipso effect,' a long-observed, yet little-invoked, mechanism for ligand-to-metal charge transfer. The arene carbon directly connected to the heteroatom rubs up against the metal d orbitals, and charge can move through space. Perhaps the best known non-NHC systems to exhibit this effect are the highly-active Buchwald biaryl phosphines, which show ipso interactions with palladium and gold, among other metals. Cavallo and coworkers compare electron density maps (the trippy blue-and-red models, above R) between cationic and neutral metal states, and note a huge red splotch of π-to-d donation (see d) from the NHC orbitals to the metal.

NHC electronics lower intermediate energies
Source: Cavallo, JACS ASAP

But wait, there's more! The authors apply this model to previous observations in Ru metathesis chemistry, then extend the metaphor and tackle Pd biaryl coupling. As shown in the graphic (left), they calculate a ~3 kcal / mol difference for the first catalytic intermediate, depending on the electronic environment of the NHC used. For a throwaway closing line, they let us in on a final trade secret: this effect could be used to stabilize lots of high-valent metal species...do I hear any calls for nickel (IV) chemistry???