2015 JLC New Year's Resolutions

And so we close another year on the chemblogosphere. Instead of recounting the highs and lows of 2014, I've decided this year to focus on what lies ahead for Just Like Cooking.

A goofy, fitting send-off to 2014,
courtesy of the San Fran ACS Meeting

Three areas I'll try to focus on for 2015:

1. Photocatalysis. It's exploding in all areas of chemistry, with new complexes and new (old) dyes appearing daily. Hopefully 2015 will show more light-promoted reactions as key steps in total syntheses.

2. Antibiotic Development. Dire predictions swirl around our readiness, as a species, to defend ourselves against the ever-evolving horde of microorganisms surrounding us. Hopefully 2015 - whether by luck or skill - finds new molecules to address this challenge.

3. Alternative Careers / Leaving the Lab. (Refer to my apologia from a few weeks ago...)



Wishing you and yours a happy, healthy start to 2015!
See Arr Oh

Two New Knights of the Periodic Table

Sir Martyn Poliakoff (RSC)

Hearty congratulations to two chemists receiving 2015 Honours as Knights Bachelor "for services to Chemistry."

Sir Martyn Poliakoff, Professor of Chemistry at the University of Nottingham, and star of the Periodic Table of Videos.

Sir Simon Fraser Campbell, former senior VP at Pfizer, who helped to discover drugs Viagra, Norvasc, and Cardura.

Scientists recognized with OBEs "for services to Chemistry" included Prof. Ian Mark Mills (Reading) and Prof. Kenneth Richard Seddon (QU Belfast).

Sir Simon Fraser Campbell (Nature)

"Gatekeeping" in Intro Chem Lab

Over at Chemjobber, there's an interesting discussion around "gatekeeping" - intentionally using introductory science courses as weed-outs to restrict access to higher-level material - and whether anyone actually does this in practice. Although I don't think of my experience in these terms, I'll relate my recollections and let readers judge for themselves.

Stone walkway, 2014

At Big State University, I was part of a teaching assistant (TA) team tackling Chemistry 101 lab. These were classic experiments: density, dilutions, diffracting light, quantitative analysis, titrations, measuring exotherms. TAs not only ran labs, but lectured beforehand, graded reports, filled out student evaluations, and tallied final grades. 

While the content wasn't enough to weed out dedicated students, the lab policies certainly may have been. The implied ideology went: "if you can't follow these rules now, you'll never cut the higher-level labs." 

Pass in a report 1 minute past the start of lecture? Zero. 

Handwritten report? Zero.

Blatant disregard for lab equipment? Zero.

Show up to lab without proper PPE? Go home. 

If a student had not replaced broken glassware by semester's end? Fail.

Evidence of plagiarism from the lab manual or suspected from others' reports? Fail. 

Miss the final exam? (Yes, a final lab exam...) Fail.

Though the TAs tried valiantly to corral teach the ~400 students who came through our section each semester, my honest memory was that we usually kept fewer than 250 by term's end.

Merry Christmas | Happy Thursday

Merry Christmas to my wonderful, interactive, patient readers. It's been a great year over here.
(If Christmas isn't something you celebrate, happy Thursday!)

If you're looking for something holiday-themed - and don't feel like resorting to Google - try these:

Look, I made the tree this year!

Chemistry of Tinsel

Chemistry of Snowflakes

Chemical Aroma of Christmas Trees

Holiday Organic Synthesis

A Chemjobber Tradition - The Letter Home

ScienceGeist's Chemistree

I have a long week coming up, and a merry backlog of topics to write about.

More posts forthcoming!

Dona nobis pacem,
See Arr Oh

Greener Nylon Synth? Just Add UV and Ozone!

"Any sufficiently-developed technology is indistinguishable from magic" - Arthur C. Clarke

Looks like we'll soon have a more straightforward way to make stockings, zip-ties, and tire belts. 

Adipic acid, a six-carbon diacid representing one of the "sixes" in Nylon 6-6, apparently takes quite a bit of industrial "elbow grease" to make. The current process, starting from cyclohexane, requires cobalt, manganese, copper, and vanadate salts, high pressures of oxygen gas, and hot nitric acid. Out the other side, its responsible for 5-8% of the nitrous oxide we humans spew into the atmosphere each year.

From Science 2014, Hwang and Sagadevan

Now, researchers Hwang and Sagadevan (National Tsing Hua University, Taiwan) believe they have a better method. Reporting in this week's Science, the two disclose a method that sounds so much simpler: flush a sample of cyclohexane with ozone and UV light, and, presto! Solid adipic acid at the bottom of your reactor. No metal salts, no nitrous oxide, no high pressures or temperatures.

Wow, that looks a lot simpler.

The researchers note that zapping ozone produces both singlet oxygen, ¹O₂, and a single singlet oxygen atom O(¹D). The highly reactive single singlet (say that three times fast!) can easily insert into C-H bonds, and, since it seems to prefer insertion next to an already-oxidized carbon, the diol, diketone, and finally diacid products are formed preferentially.

Applause, please: Look at this beautiful pictorial SI!
Twice, in two days.

Just for fun, Hwang and Sagadevan crack open some larger hydrocarbons, and check the selectivity of alkyl-functionalized rings and aromatics. There are tantalizing possibilities here that I'm sure, given the ease of this reaction setup, most organic chemists will already be trying: how do complex natural products* react under these conditions? If anyone tries it this weekend, please drop me a line.

--

*For that matter, I wonder if this pathway is operative in human tissues under physiological conditions? Sunlight does have some 300 nm band, and we certainly come into contact with ozone out in the wide world. Hmm.

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? : )

...and now for Something Completely Different

I've been mulling over a version of this post for far too long, so here goes:

It's time to make some changes around here.

As I've quipped before, all careers in chemistry eventually leave the lab. Nearly gone are the days of the frizzy white-haired scientist holding aloft the shimmering vial and shouting "Eureka!"

Today, we often find ourselves in transition: Post-docs become professors, who write papers and manage a group. Bench chemists move into operations or regulatory roles. Technicians re-train and become patent clerks. Even med-chem project leaders eventually hire enough people that they think project strategy and logistics far more than they shake sep funnels or run TLCs.

Adapting to change can be ruff.

And so it is with me -- I find myself at a career inflection point. My Twitter handle reads: one foot in, one foot out. Ever wondered what I meant? It means I'm no longer your friendly "workaday synthetic chemist." I'm still in a role where I think about chemistry daily, and I apply my skills to solve problems. . . I just don't run reactions with my own two (gloved) hands.

At this juncture, one feels a complex mixture of emotions, to be sure:

Excitement, to learn new things and travel more frequently.
Embarrassment, that I've been blogging about chemistry and yet haven't touched a rinse bottle of acetone in months!
Fear, that I won't be as good at this new venture as (I thought) I was at synthesis.
Resolve, that I'm going to buck up and do my best, despite my nerves.

So, gentle readers, please bear with me. I'm going to probably shift away from lab stories and synthetic methods, and try to return to the theme of my very first post:

"This blog will reach out to the wider world about science, and especially chemistry."

I may write more stream-of-consciousness posts about navigating complex organizations, managing expectations and people, and thinking strategically. I may say "vision" or "collaborative."
[Oh great, thinks half my audience, he's really drinking the corporate Kool-Aid now!]

Fine - I'll also still write about chemistry. When something really awesome catches my eye : )

Thanks again, as always,
See Arr Oh

--
I admire and applaud all who made it to the end of this short chautauqua. If you'd like to leave any kind advice on steering one's blog in a new direction, comments are open!

Fond Farewells

Today marked endings* (of sorts) for two prominent members of the chem-blogging community.

First up, Carmen Drahl - intrepid Chemical and Engineering News reporter - announced she was stepping down:

Folks- I'm leaving @cenmag 1/2/15, to travel and explore. I can't thank you enough for making this gig an adventure. 1/3
— Carmen Drahl (@carmendrahl) December 9, 2014

Just a few hours later, Paul Docherty of Totally Synthetic, arguably the blog that gave rise to post-peer-review in synthetic chemistry, called it quits to focus on a burgeoning informatics career.

I'd like to wish both Carmen and Paul a teary, heartfelt good-bye. After all, they both got me into blogging; see my Haystack and TotSyn guest posts. Moreover, they built the bridge from the Tenderbutton / In the Pipeline / The Chem Blog era into the rich and diverse bloggy landscape we enjoy today (see just a fraction of them, in my blogroll, at right).

Best wishes to both Carmen and Paul as they ride into the Internet sunset.

It's a road, off in the distance. Like a metaphor, or something.

--

*But not for me. Sorry, chemblogosphere, you're stuck with the pup for yet another year.

Confusing 'Chemistry' Image of the Day

This image appeared in an NPR Shots blog post outlining the CDC's recent recommendations on male circumcision:

Source: NPR News / Corbis Images

Please help me understand - What on earth do the floating molecules have to do with this story? 

I grok that the image suggests two men deep in conversation. The article doesn't mention any drugs. Nor bodily substances. No pheremones, hormones, biomarkers, or viral particles enter the conversation. Just another case of stock images gone wrong?

'Magic Berries' Pack Phorbol Punch

Could plant extracts still surprise us? "Magical rainforest berry kills tumors with single injection" read last month's FiercePharma headline. The Guardian reinforced the hype, narrowing down the berry's source (Queensland, Australia) and the compound: EBC-46*, promoted by local biotech QBiotics and tested by colleagues at the QIMR Berghofer Medical Research Institute.

Digging down to the PLoS One article behind the research, I uncovered the drug's structure and proposed mode of action. Now, where have I seen a compound like that before? Oh, right! Ingenol. Both compounds belong to the phorbol ester family, and both appear to activate protein kinase C, spurring tissue necrosis and tumor shrinkage when directly injected into mouse skin cancer lesions.

The authors indicate that they're preparing GMP product for Phase I human trials; whether that's derived from magical rainforest berries - or just plain process chemistry - hasn't been disclosed.
Stay tuned.

--
*The published structure doesn't match the molecular weight (562.25 g/mol) the PLoS authors suggest, and no stereochemistry is specified. I'm guessing it's structurally similar to phorbol, and I've gently highlighted in red a hydrogen that's probably supposed to be a methyl group.

WWWTP? "Always Sunny" Edition

Charlie, Mac, Dee, and Dennis, the self-involved social group of FXX's It's Always Sunny in Philadelphia, would never advocate cautious, logical behavior as the best way to approach a situation. The dark humor that inevitably follows their ill-advised actions propels the show.

With nine seasons on the books, nothing's really changed. In the recent episode "Flowers for Charlie" - likely an homage to the late Daniel Keyes* - two scientists approach slightly-below-average Charlie with a pill ("a cerebral enhancement formula") to increase his IQ. Look at the chemical structures on those chalkboards!** Would you take medicine from these men?

Texas carbons, Wyoming nitrogens, and...a propeller?
Source: Fox Entertainment

Perhaps these "scientists" should win a Nobel for the first-ever aromatic spirocycle.
Source: Fox Entertainment

Spoiler Alert! After faking his way through French, philosophy, Beethoven, Tolstoy, chemistry, chess, Mandarin Chinese (not to mention a terribly put-on English accent), it turns out Charlie remains slightly-below-average, as reinforced by several chuckle-worthy graphs.

Colored fluids in condensers...sigh.
Source: Fox Entertainment

---
*If you've never read "Flowers for Algernon," don't walk - RUN - to your local library and grab a copy.
**They're like prehistoric whiteboards.

"Unknown Unknowns" in Synthetic Biology

Update: Ash (@curiouswavefn) found a similarly structured article, this one in J. Med. Chem.

Somehow, I don't recall seeing this gem anywhere on the chemblogosphere...

Famed natural products chemist Jon Clardy wrote a 2014 perspective article in ACS Synthetic Biology. Interestingly he structured the content after former U.S. Secretary of Defense* Donald H. Rumsfeld's 2002 "There are known knowns" testimony. Remember it?

"...as we know, there are known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns -- the ones we don't know we don't know."

Per the Clardy review, artemisinin (antimalarial) represents one of synthetic biology's well-researched "known knowns." Moving synthetic gene clusters for cryptic metabolites into more easily-cultivated host organisms meets the "known unknowns" criteria, whilst uncovering novel natural products with novel gene clusters and unidentified biological roles captures syn-bio's "unknown unknowns."

--
*And, lest we forget, former CEO of Searle Pharmaceuticals - poetically apt, here?

Chemistry Bumper Cars - Chris Walsh to Stanford?

Earlier tonight, while combing through the ASAPs, I came across an interesting situation:

This paper (http://t.co/VHLzS2HbOO) seems to suggest that Chris Walsh (http://t.co/JfvajzKoyH) is now at Stanford. Can anyone confirm? #move
— See Arr Oh (@SeeArrOh) November 11, 2014

Usually. the chemblogosphere catches major moves fairly fast, but have we missed this one? Perhaps this is a "courtesy appointment," though I can't find any mention on Stanford's site.

Anyone know anything?

Candid Chemistry - 2014 Edition

Occasionally, readers will send me funny pictures that somehow capture the chemistry cultural zeitgeist. Here's some from the last few months:

At MIT, you can apparently chain your bike to a caffeine molecule!

Seen at UC-Berkeley: the ultimate chemical Doom tribute
(...to this guy)

Still frame from LeVar Burton's charity read of Go the #*&@ to Sleep
Does anyone recognize the (fake) elemental symbol poster? Geordi would never approve.

Attn, Chemjobber: from Austria, a promotional poster extolling the virtues of chemical employment!
(and a hip song to go with it!)

Heartfelt thanks to everyone who sent one in. Keep 'em coming!

(seearroh_AT_gmail)

Invisibly Important

Who does more important work: The scene-stealing front man, or the patient show-runner backstage?

Sumac in Fall, 2014

Writing at the New York Times "Motherlode" blog, author David Zweig posits that, in an era of attention-grabbing occupations - Internet whiz-kids, Wall Street financiers, American Idols - the real winners may be those who select the quiet, thoughtful "enabler" roles behind the scenes. He claims that, though they may not get the glory, such "Invisibles" end up better paid and more highly satisfied with their chosen stations.

Though Zweig volunteers occupations like structural engineers or quantitative analysts, I'd offer that most important roles in scientific research belong equally on his list: Spectroscopists. Molecular modelers. Patent examiners. Grant writers. Purification staff. Procurement. Health and Safety. Administrative assistants. Graduate students.

If you get a chance today, think about the Invisibles that help your science to succeed.
And buy that mass-spec guy a beer, already!

Friday Fun - Maitotoxin Watch

For those keeping tabs on K.C. Nicolaou's potential career capstone, the group has published another fragment (QRSTUVWXYZA') of the ladder polyether maitotoxin. By my count (and thanks to their handy graphic, below), they've now formed 30 of the 32 requisite rings, meaning we'll likely see a completed total synthesis in the next few years.*

Top: Maitotoxin
Bottom: Previously disclosed fragments
Source: Nicolaou et.al. | JACS 2014 ASAP

When Nicolaou's group announced the move to Rice, one of my first thoughts was "who gets to personally chaperone the maitotoxin fragments to their new home?" I'm picturing combination-locked black suitcases handcuffed to postdocs' wrists, but perhaps the samples just went in the back of a U-Haul truck with all the other lab equipment.

Happy Friday,

See Arr Oh

--
*Assuming they can work out the ring fusion and selective sulfate chemistry - not trivial tasks by any means!

Strange Cover Art

A small part of me remembers a time before journal articles could all be accessed online. Back then, the cover art -- a creative expression of some of the newly-reported research between the covers -- could swing you towards one journal over another as you milled around the musty library stacks.

Source: Wiley-VCH, c. 2014 / ACIEdoi: 10.1002/anie.201409223

Nowadays, we've lost some of that artistic tradition, save for notable standouts Nature Chemistry and Angewandte Chemie. Hence, my confusion when looking at this week's Angewandte cover art - does anyone understand what's going on here? 

Best I can tell, this graphic is a nod to Prof. Younan Xia's excellent overview of the benefits and risks inherent to nano-scale research. But the graphic appears (to me, anyway) to resemble two angry Pokemon fighting over the sword from Legend of Zelda. About the only chemistry I see? Blink, and you'll miss it: along the blade are five tiny emblems meant to represent common nanostructures such as carbon nanotubes or micelles. 

Readers, am I missing something obvious here, or does this not really communicate the depth of Prof. Xia's review issue?

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.

C'mon, Let's Twist Again, Like We Did (This) Summer

Dirk Trauner: natural products chemist, vision researcher, neuropharmacologist,
. . . carbon nano-tube enthusiast?

Apparently, it's "crazy saturated hydrocarbons" month here at JLC. An astute observer clued me in to the Trauner group's latest pursuit - polytwistane. Studied for five decades by organic chemistry pioneers such as Whitlock, Deslongchamps, Oka, and von Rague Schleyer, twistanes have been tricky to coax into existence, owing to their propensity to rearrange into more stable adamantane.

In a 'gedanken' (thought) experiment, Allen, Schreiner, and Trauner mentally "add" bridging ethane units to twistane, stretching it out into a pseudo-helical oligomer (Chem. Eur. J.):

Chem. Eur. J. 2014, 1638.

Some fascinating molecular motifs fall out of their modeling studies. For example, unlike adamantane, polytwistane has three distinctly different C-C bond lengths, a factor chalked up to strain energy. However, it's in no danger of falling apart - the researchers calculate a "very modest" strain energy (~1.6 kcal / mol CH). All the hydrogens occupy positions on the outside (convex) surface of the tube. Finally, note that polytwistane is formally a polymerized version of acetylene, which we'll come back to later.

Emboldened by these in silico  results, Trauner and team take to synthesizing a basic unit of polytwistane, so-called "tritwistane" (Org. Biomol. Chem.). Starting from laticyclic polyenes -- think bicyclo[2.2.2]octene, connected end-to-end -- the researchers try a variety of electrophilic conditions to form the bond in question. Eventually, a combination of bromination / radical reduction produces the simple tritwistane oligomer:

Org. Biomol. Chem., 2014, 108.

At the close of this paper, Trauner deadpans that "attempts to synthesize polytwistane . . .from acetylene itself are ongoing in our laboratory..." Sounds like a tough nut to crack, but if he succeeds, he and his collaborators will have access to a rather rigid, narrow, twisted new material certain to possess interesting properties.

----
*Don't know the song in the title? Say hello to Chubby Checker!

Help Wanted: "Working Hours" Survey

Ofer Kedem, a postdoctoral researcher in the Weiss lab at Northwestern, has posted a survey to try and get a handle on the daily grind for academic chemists. He and his colleagues hope to garner enough data to publish their results in an open-source journal.

In the interest of statistical significance, won't you help them out?

HERE'S THE LINK.

(Thanks!)

Remember When?

Remember how we used to generate research reports?

"The scientist in a pharmaceutical company prepares his compound documents, using a variety of text and graphics systems, in a laborious cut-and-paste procedure, and transmits a hard copy to a records center, where photocopies and microforms are made and indexing takes place. When the end-user wants to retrieve his report, he asks an intermediary to do a search. The result will be a report number or access address. The hard-copy report then has to be manually retrieved, perhaps copied or printed, and delivered by mailman to the end-user. . . it is also evident that research end-users are not accessing full-text online databases to any large extent."

 - From J. Chem. Inf. Comput. Sci., 1991

It's truly amazing how quickly technology has accelerated online publication in the intervening two decades.

Public library lintel, USA

Update (Aug 3) - Derek Lowe weighs in:

@SeeArrOh Yep, that's how my continuation exam in grad school was done. Typewriter, plastic template, rub-on letters. Just before @Chemdraw.
— Derek Lowe (@Dereklowe) August 4, 2014

Honoring Carlos Barbas

Carlos F. Barbas III, a synthetic chemistry professor at Scripps, passed away just over a month ago. I remember first reading about his proline-catalyzed aldol reactions early in my graduate career; I assumed he'd one day share a Nobel Prize for organocatalysis.

In Angewandte Chemie, Phil Baran eulogizes Prof. Barbas well. I hadn't known, for example, that he had earned almost 60 patents (!), had founded three companies (Prolifaron, CovX, Zyngenia), and had mentored hundreds of students, all before the age of 50. Unbelievable.

To close, I'll use Prof. Baran's words:

"He had so much to live for and lived life to the fullest when he could.  

He would want all of you to do the same."

Takei's Target Audience

George Takei, an American actor / activist perhaps most famous as "Sulu" from Star Trek, inadvertently let slip a fantastic bit of advice to Terry Gross on Fresh Air (emphasis mine):

Takei: outreach specialist, helmsman

"I've been on speaking tours advocating for equality for the LGBT community. But what we noticed was I was already talking to the converted — either LGBT people or allies — and what we needed to do was reach what I maintain is the decent, fair-minded, vast middle — people who are busy pursuing their lives and don't stop to think about other issues."

Just replace "equality for the LGBT community" with "chemistry for the general public," and you stumble on a very familiar problem in the blogosphere; communication to that "vast middle" is something we ponder every day.

Cubanes! Get Your Cubanes, Here!

A cube of med-chem cubanes**

It's not often you see drug candidates advanced with cubane substructures.* A collaborative group from the UK branch of AstraZeneca and Oxford University aims to change that: a report in Organic Letters indicates they've produced gram-scale quantities of cubane derivatives with common med-chem handles already "baked in."

Starting from a 1,4-cubane diester, Burton, Davies, and Wlochal take turns elaborating each side into thiazoles, beta-diketones, nitriles, amine salts, and ynones. Though more cautious readers might expect the cubed synthons to go up in smoke, they actually seem to survive fairly rigorous conditions - boiling water, phosphoryl and oxalyl chloride, TMS triflate, LDA.

I'd be most interested to hear from any readers who integrate these new building blocks (sorry, couldn't resist!) into their research. It's hip to be...cubic.

* On Twitter, CJ (rightly) points out that the authors could have done some DSC (stability) and solubility assays, just to put minds at ease that these synthons really could be integrated into a drug campaign.

**Not a real substance (but wouldn't that be something???)

So, what's new?

A few days ago, one of my coworkers at the new job asked me to tell them what the newest, coolest trends in synthetic organic chemistry were. And, I readily confessed, even though I write this blog, I'm still in the dark about exactly what folks find exciting, even week to week!

New ligands for palladium? Been there.

Protecting group-free synthesis? Done that.

SF5? CF3? Polyfluorination? Old news, now.

Even cobalt, which seems to be the new darling of the catalysis community, feels like it's taking a comfy chair in all my favorite journals.

So, tell me, Internet: What's the newest, coolest stuff you've heard about?

Déjà vu, LPU

Remember when I posted about the highly-similar cyclobutane insertion chemistry coming out of the Cramer group? Well, a new contestant has just been published in ACIEE:

Source: Cramer, ACIEE 2014

I jumped down the rabbit-hole of the Supporting Information, and returned with these two "general" procedures - blink, and you'll miss the differences!

Source: Cramer et. al., ACIEE 2014, February

Source: Cramer et. al., ACIEE, 2014, July

Same catalyst precursor. Same ligand (well, different enantiomer). Same solvent. Same time. Similar reaction temps and purification conditions. Now, I'm not saying that the Cramer group shouldn't have published this paper, but in the same journal? With essentially the same substrates?

Does anyone else believe that these could have been published together, in a single high-impact paper?

"Cantrill-ing" Hits the NY Times

Apparently, U.S. Senator John Walsh has been accused of plagiarising a final assignment for his Master's degree. And how did the New York Times cover this story? Why, by literally "cantrilling" the paper!

Source: NY Times

Remember us all when you're famous, Stu.

Review: ChemBioDraw 14.0

Dear ChemBioDraw* Ultra 13.0,

Listen, we had a good run together. But I've fallen for another: ChemBioDraw Ultra 14.

My good friends at PerkinElmer (PKI) were kind enough to grant me trial access to their spiffy new chemistry drawing software. As an avid user since, oh, say, ChemDraw Pro 4.5, I feel confident in stating that this version wins all around for smoother operation, better templates, easier file export, and better shortcut keys.

So, I figured what PKI really wanted me to do most was to try and BREAK ChemBioDraw 14.0
 . . .if I could. Did I succeed? Let's talk a walk through the software and find out.

CBD 14.0 means NEVER seeing this screen again (hooray!)

Starting at the top, I figured I'd check the "What's New?" link in the help menu. One thing I appreciated more than I thought? ChemBioDraw 14.0 directing "Help" queries into the appropriate section of the User Guide. Version 13 still spawned its help window inside Windows help, with the infamous purple booklets leading you down wild goose chases of clunkily-presented information.

Drawing hasn't changed much since 13.0. At least the text direction auto-correct -- which drove me batty in former iterations -- seems to have been tweaked; the system now opens my older drawings the way I typed 'em in originally (hence, below, attaching pasta sauce to a scaffold in place of a sugary placeholder).

I promise this made sense in earlier ChemDraw versions...

The CBD 14.0-to-SciFinder jump works much more smoothly than I had anticipated. For those of us who shuddered through dial-up desktop versions of SciFinder in the late '90s, this version feels like the sleek Lamborghini of the search world. After drawing (or importing) my structures of choice, I lassoed them up and pressed the little "SciFinder diamond" on the top toolbar. Within about 5 seconds, a new window opened with the standard exact / substructure motif. Two clicks later, I'd be deep into the primary literature.

So, my goal was to break the system, right? Here's a logical place to try - I attempted to load each and every complex structure I had drawn since starting my fledgling blogger's career, around 2009 or thereabouts. Again, I was amazed by the speed and accuracy of the SciFinder pop-out, which returned roughly 90% of the correct molecules I'd searched for (below):

From this 2011 post

From this 2013 post

From this 2014 post

However, it's not all bubbles and sunshine. Two of my molecular queries bore no fruit**; perhaps they're too new to have been uploaded into CAS's databases yet. But one thing remains tricky: drawing and searching for metallocenes. Along with their new push into biology clip art, ChemBioDraw has a renewed focus on making sure you've got those sandwich compounds properly aligned.

Sigh. If only I remembered what they were all supposed to be...

Now, even after aligning my query using the proper template, SciFinder makes a mess out of it.

From this 2012 post

So, obviously I went looking for things to break, and found some rather limited examples. Honestly? The rest of the program works pretty well. And writing this review gave me a wonderful opportunity to poke and prod at the product in ways I hadn't in far too long.*** I finally realized you could change the solvent on the NMR predictor! I played around with expanding and collapsing peptide and RNA strings. And the post-drawing mods to more complex peptides, like disulfide and lactam cross-linking? Much better.

Found on p. 126 of the User Guide. (Get it?)
I'd like to shake the hand of the person who slipped this in...

R.I.P., Optimizing Octopus

I will take this final moment to remember a long-lost piece of ChemDraw lore. Once upon a time, to "clean up" one's structures, the icon looked something like this (right). I've heard it referred to as a jellyfish, a squid, a broom (no!), but I always knew it as a friendly little octopus. With CBD 14, any doubt about its brushiness has been cast aside with a full-out icon redesign.


Looks great, guys. Now let me think about more ways to use it for actual work!

Thanks again to Philip Skinner and PerkinElmer for the chance to review the software.

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*For other blog reviews of ChemDraw products, see Jess The Chemist, Andre the Chemist (no relation), or Chemjobber.

**Here's the structures that returned empty SciFinder searches. Both compounds (left, right) were first reported in 2014.

***P.S. I never knew you openly solicited beta testers for these products...gimme a call sometime, PKI!