Interlude

It's so refreshing that Spring has finally sprung in Big City, USA.

This one was snapped by an observant reader whilst on a
hunt for a new couch. Cost of each? $30.

More Pictures in Supporting Information? Please!

Just stop what you're doing right now, and look at the gorgeous reaction setups in this Nature SI.

From SI page S16. Source: Nature / Baran lab

My kudos to Phil & co - they sure do capture a good visual chronology of their reactions!

Also prompted one of my more tongue-in-cheek Twitter exchanges in recent memory...

@P212121 - Would you say then (wait for it...) that it was JUST LIKE COOKING? @Dereklowe @Chemjobber

— See Arr Oh (@SeeArrOh) December 18, 2014

Do these pics remind you of anything? : )

Friday Fun - WWWTP? NASA Secret Food Edition

Pretty sure this counts as an epic Google Ads failure...

Happy Friday,
See Arr Oh

Valleytronics? More 'Borrowed' Phrasing...

Update: 8/9/13: Editors respond...

@SeeArrOh Thank you so much for this. We have taken notice, and we will act as soon as possible. @NatureNano
— Nature Materials (@NatureMaterials) August 9, 2013

***

Tonight must be "Twitter tipster" and "authors behaving badly" night!

From the 'News & Views' pages of two vaunted Nature publishing journals come the latest chunks of potentially plagiarized text. Please open your browsers to this 2012 Nature Nanotech article, and then this 2013 Nature Materials piece. Now, I'm not going to pretend I'm a p-chem or 'valleytronics' expert, but I can certainly spot duped text on command:

NN paragraph 2:

"Electrons travel through a crystal as waves, which are described by a momentum (which is a continuous variable) and a spin (which is a discrete index). It is possible for a crystal to have two or more crystal axes that differ in their orientation, but are otherwise identical: such axes can support electron waves that are also identical apart from their direction (or, more precisely, their momentum)."

NM paragraph 2:

"Electrons travel through a crystal as waves, which are described by a momentum (which is a continuous variable) and a spin (which is a discrete index). It is possible for a crystal to have two or more crystal axes that differ in their orientation, but are otherwise identical: such axes can support electron waves that are also identical apart from their direction (or, more precisely, their momentum)."

Missed the changes? There are none; this is lifted word-for-word.

Another, perhaps?

NN graf 3:

"As in spintronics, there are two main challenges facing researchers trying to make valleytronic devices. The first is restricting electrons to one quantum number, which for valleytronics means localizing them to one momentum valley. This is also referred to as achieving valley polarization. The second challenge is to detect the valley-polarized current."

NM graf 3:

"As in spintronics, there are two main challenges facing researchers trying to make valleytronic devices. The first is restricting electrons to one quantum number, which for valleytronics means localizing them to one momentum valley. This is also referred to as achieving valley polarization. The second challenge is to detect the valley-polarized current."

Hope you didn't blink much, 'cause that one's identical, too.

Although I don't excuse it, I can understand the pressure to grab text under a research deadline, or to emulate a master author. But for news write-ups?!? Looks like someone's got some 'splaining to do...

New Tricks for Old Reagents: Oxygen Everywhere!

Passed a time, not too long ago, when if you wanted to oxygenate a selected C-C or C-H bond, you had to jump through several hoops: Over-oxidize (read: DESTROY!) then reduce again. Convert it to another functional group first, then use an expensive catalyst. Use toxic heavy metals (Cr, Hg, Pb, anyone?) in their highest oxidation states...and, oh yeah, heat the heck out of it.

The past decade has seen kinder, gentler oxidations emerge in rapid succession. Cobalt. P-450s. Iron. Now, two recent papers bring new wrinkles to the oxygenation of organic molecules in unexpected ways.

The first, from the Concellon / del Amo group in Org. Lett., relates a neat trick performed by Oxone, usually a reagent reserved to make other oxidants.

The researchers deal with their serendipitous discovery with humility and class:

"This work was not originally intended..[but]...was worth studying. [We] remark that Oxone is a crystalline solid oxidant, easy to handle, non-toxic...and, above all, stable and cheap."

All great reasons to run these reactions, which are formally derivatives of the classic Baeyer-Villiger reaction. They blast through a brief substrate table (26 entries, 33-95% yields), and seem pretty excited about investigating the mechanism.

The second reaction, hot off the Nature presses, involves another legacy reagent: phthaloyl peroxide. I suspect the Siegel group was looking for sp3 C-H activation conditions, but instead discovered a serendipitous site-selective arene activation, reliably producing phenols.

The reaction works across a broad functional group palette - azides, silyl groups, boronate esters, primary halogens - that other oxidants would tear apart. They ultimately do about 50 substrates, including 3 natural product-like scaffolds, with yields ranging from 45-95%.

Deciphering the mechanism requires Ken Houk's computational super-powers. The researchers discover a "reverse-rebound" mechanism operates, meaning an oxygen radical from phthaloyl peroxide adds into the ring, the electron bounces around in the pi cloud, and then ejects the ipso hydrogen in a two-step process. Interestingly, other radical oxygen oxidants (di-benzoyl peroxide) led to primarily sp3 oxidation, showing that the structure of the radical precursor plays a big role here.

Friday Fun: Timing = Everything

Looks like a snowy weekend for those in the Northeastern U.S. Predictions for the New York-to-Boston area, which includes a large swath of the biotech / pharma corridor, expect anywhere from 8 to 24+ inches of snow over the next 2 days. 

Well, to paraphrase one of my Twitter colleagues, Pharma 'laughs at snow the way it laughs at stable jobs.' Thus, many of you will still be venturing out into the Snowpochaosalypsemageddisaster. Hopefully, you're already stocked up on salt, sand, and dry goods. 

If you're one of the 'lucky few' who've already closed up for the day, Nature has you covered: a perfectly-timed Top Ten list for future ice and snow research! Author Thorsten Bartels-Rausch says it best on his research page: "Snow and ice are chemically active." From trapped gases to metal reduction, there's a fascinating molecular interplay within frozen water matrices. Go have a look!

Happy Friday. Stay safe!
-SAO

Molecular Machine, Unadorned

So, chemists, you've probably seen this article over at Nature News, which reports a "molecular robot" capable of traveling down a track to assemble a small peptide. Pretty awesome, right?

Source: Nature News | Leigh Group, University of Manchester

Now, that's a cute cartoon, but what's behind the scenes? Intrigued, I hustled over to Prof. Leigh's Supporting Information, and found the real gizmo, spectra and all. Take a look!

Source: Science | Prof. David Leigh

(Yes, that's a carbon NMR, for a single compound.)

I will never complain about characterizing small-molecule drugs again!

Strange Brews

While leafing through the latest magnum opus by Prof. Phil Baran and his Super Group (Nature, 2012, 492, p.95), I came across this playful graphic* near the bottom of page 4:

Source: Nature 2012 | Baran group, Scripps

Yes, that's right: Phil's "toolkit" chemistry for site-selective radical additions works in buffer, cell lysate, or oolong tea. Sounds like we need a few more entries in B.R.S.M.'s "Conditions You'll Never Try" post!

Mmm, delicious solvent...
Source: forbes.com

Perhaps a story I tossed out in his Comments section bears repeating: I once attended a conference where Profs. Paul Wender and Kazunori Koide spoke on alternate days. Wender went first, and mentioned in passing that one of his group's specialties (I think it was Rh [2+2+2], but correct me if you know otherwise...) could be performed in beer. Not to be outdone, Dr. Koide called his group the following morning, and arranged a hasty trial of his transition-metal detecting fluorescent sensor in Starbucks coffee.

Escalation followed. By the end of the conference, everyone had rung up their labs to try ever more exotic solvents, ranging from wine to paint thinner, then finally to whiskey. As explained in Adam Rogers' fantastic 2011 piece "Mystery of the Canadian Whiskey Fungus," this aged, distilled melange of organic compounds should foil up all but the most robust reactions; I'm fairly certain the reaction - another metal-catalyzed cyclization - still performed around 40%. Not too shabby.

*Just noticed that Bethany Halford beat me to it, at least as far as the tea!

Mushroom Pharmacology...as seen in USA Today!

'Magic' Mushroom G. lucidum
Credit: Wikipedia user Eric Steinert

While peering through the evening's Twitter foliage, I spotted a fungal gem among the fallen, matted links of my "social media ecosystem." Following the trail blazed by Matt Herper and Shrikant Manti, I hiked over to USA Today's ScienceFair blog to read "Chinese 'mushroom of immortality' genome mapped," by Dan Vergano. Great title, but what about the post itself?

Vergano explores the recently-reported genome of the lingzhi / reishi mushroom (G. lucidum), an Asian traditional medicine with a rich pharmacopoeia. The reader gets a brief summary, slightly sparse and unstructured - note the oft-used hook "the study authors note," a sure sign that we're venturing into uneasy territory - and a few throwaway terms, like "Triterpenoids" [sic] and "more than 12,600 genes" (that's a mighty round number for any organism, I'd say...). The piece feels strangely unfinished, like it lost all its momentum after the initial burst from a catchy headline.

Laccase 'lights up' lignins!
Source: Mashed-up from Zeeco and U-Maine

So, it's off to Nature Communications for a more thorough look at the item of interest. Sure enough, looks like the bulk of the USA Today post simply paraphrases the opening paragraph of the manuscript! From mentioning "400 compounds" to a passing remark about biofuel production, it's all there. But where did the strange '12,600' value come from? We'll turn things over to lead authors Chen, Xu, and Liu: Table 1 states that the G. lucidum genome contains 16,113 protein-coding genes, and further down (Fig. 2b), a Venn diagram shows that 12,646 genes are expressed throughout the fungus' life cycle. Now we're getting somewhere! The authors go on to discuss bioactive polysaccharides, mysteriously absent from the post, and then the variety of -ases that contribute to the 'enzymatic combustion' of wood lignins...the best quotes are always buried!

He knows fungal gene mapping
Source: KT5 blog

Instead of heaping on further criticism, let's fill in some blanks here. Triterpenoids aren't so much individual compounds as a family affair - the catch-all term refers to any compound produced by stitching together six isoprenes, a small 5-carbon synthon common to all plant life. Perhaps you've seen lots of triterpenoids without recognizing them: lanosterol, the precursor to human sex hormones testosterone and estrogen, falls into this class. If you're more chemical biology-inclined, check out the Discussion, where the authors use gene sequence and mapping technologies - SMURF, anyone? - to predict zinc-finger nuclease clusters, and then discuss the secondary metabolites arising from a wide variety of expressed cytochrome P450 (CYP) enzymes, the original biochemical bandits behind selective C-H oxidation. 

(P.S. - This mushroom really represents in the primary literature: a search for the term "lucidum" only brought up 140 hits at ACS, but this ballooned to 2,955 at Wiley, and 5,000+ at ScienceDirect!)

Press Release

(08:00, USA; 13:00, London GMT, For Immediate Release)*

 'Just Like Cooking' to Merge with Nature Publishing Group; New Journal 'Nature Cooking'

Just Like Cooking, a somewhat relevant chemistry blog based in the United States, has agreed in principal to merge with Nature Publishing Group (NPG), London. The union will result in a new publication - Nature Cooking - set to premiere in 2013 with blogger See Arr Oh as Editor.


Said Nature Chemistry Chief Editor, Stuart Cantrill: "We were thinking about ways to grow the brand beyond simple chemistry and biology, and hit upon this idea whilst eating LN2 ice cream at Chin Chin Laboratorists. See Arr Oh brings a wealth of kitchen-based knowledge, and we'll try for a real 'molecular gastronomy' flavour with this journal." Added Associate Editor Neil Withers: "Quite so."


Editorial staff will be selected from the finest food scientists and celebrity chefs (Pépin, Lagasse, and Morimoto have already signed on), and each issue will feature a fold-out pictorial of the Editorial staff dining at fine Michelin restaurants. Initial issues will explore the finer intricacies of British cuisine, including GC headspace analysis of haggis, density checks for Cornish pasty manufacture, and isolation of potent anti-cancer molecules from Christmas puddings.

Potential Nature Cooking dress code

Reaction around the blogosphere has been decidedly mixed. C&EN Associate Editor Carmen Drahl fought back tears, saying "We were about to rename Newscripts to Foodscripts, just to get See Arr Oh to stay." Bloggers Paul Docherty and B.R.S.M. both applauded the move, while Chemjobber lamented the loss: "I'm not happy, as this reduces chemical employment stateside, but if he sends me back some jammie dodgers and a Doctor Who poster, we'll call it even."


*Please see here for more information.

A Chiral Conundrum

While browsing on Nature News this afternoon, I came across a puzzling chemical graphic in the article "Frontier Experiments: Tough Science." Under the heading "Seeing through the molecular mirror," came this picture of two hands, showing the chirality around a Re center...

Source: Thomas Porostocky / Nature News

OK, I understand the point of the graphic, but I'd like to tackle a few pedagogical questions. First, has anyone ever seen a real-life compound like this? I searched Reaxys, but couldn't find any examples of a Re center bound to three different chalcogens. Closest I could find were some rhenium selenide clusters. 


Second, what's the valency around that Re center? My good buddy Wikipedia (source of all truthful information on the internet, right?) informs me that Re can have oxidation numbers from -1 to +7. Well, OK, so I'll assume double bonds between all the heteroatoms and Re (which also doesn't come up via Reaxys or our buddy Google), but I'd still question whether, as drawn, we have Re(+4), five, six, or seven!


So let's assume a stable compound...is it actually "chiral?" 


Textbooks on inorganic chemistry indicate that Re(VII) complexes with oxo ligands prefer the square pyramidal geometry. Well, you say, it has two other bivalent chalcogens, so maybe it's tetrahedral after all? My ligand field theory spider sense tells me that Re(VII) is d0, which should have a tetrahedral geometry, but I don't know enough about this peculiar complex to know if it takes on solvent molecules (becoming octahedral?) or undergoes inversion. Maybe in the gas phase (lasers!), in a vacuum, it's just a plain ol' tetrahedron.


I'm not attacking the artist, he's a graphical designer, not a chemist. And I get the message - it's a physical chemistry model experiment to show how chiral molecules show slightly different physical parameters, perhaps ones that can be measured. The designers use a single periodic column to show how molecular number assigns chirality (C-I-P convention) and to enforce a striking enantiomeric disparity. It's just hard for me, as a non-physical chemist, to go this far out on the edge.


Please, to illustrate this concept, let's use known examples (amino acids, anyone?) first, and then transition out to the edge. Then we won't suffer Feynman's cargo cult caveat: "...you should not fool the layman when you're talking as a scientist."


Update (1/5/12, 3:44PM) - I realize that the Darquie experiments referred to in the text involve (potential) formation of such a compound. I simply find "strange bedfellows" for text that leads with biological homochirality, since Re(VII) compounds are unlikely to be something one encounters in cells!


(1/5/12, 4:19) - Cleaned up text in grafs 2-3 to focus the post.