Tuesday, July 31, 2012

New Rainbow of Synthetic Firefly 'Fire'

I love deep answers to seemingly simple questions, like why grass looks green (emission spectra), or what causes "metal" smell (hand oils). I also enjoy rational drug design, the process where a hit becomes a lead through a series of well-thought and "why not?" changes. Finally, everyone likes flashy colors, especially natural ones.

Well, what if a recent paper met all three criteria? And had a catchy abstract graphic, to boot?

Look no further than the latest Angewandte Highlight, out now in the Early View section. Prof. Wei Guo and his students sum up progress towards synthetic luciferins, which are capable of bioluminescence just like the yellow-green D-luciferin many of us remember from childhood firefly collections (I'm hardly the first blogger to mention synthetic luciferins, btw. See Scheme 1 in the paper for a general luciferase reaction).

Credit: Guo et. al., ACIEE Early View
Regarding design, the chemical ground rules have been known since the late '60s:

1. Don't mess around too much with the phenol group. It prefers to be -OH or -NHR.
2. Heteroatom swaps in the two heterocyclic rings are mostly OK.
3. Don't cleave the carboxylate, or you'll turn out the light!

With these simple statements in mind, chemists have brought forth a slew of new luciferins over the past decade. The take-home message? Depending on the substitution pattern, luciferase lights up over a broad range, from deep in the red (>600 nm) up to bright blue (around 460 nm). Researchers use the new luminescers as probes, guest-starring in cellular assays sometimes reserved for the mighty GFP.

A few things caught me by surprise. First, how such tiny structural manipulations could produce such large changes to the observed bioluminescence - an S-for-Se swap gains 50 nm (red shift) whereas an S-for-N-Me buys you 100 nm...in the opposite direction! (blue shift) Second, I had no idea that there was a mutant version of luciferase - ULTRA-GLO - that not only permits high-throughput analysis, but also increases the observed light 3- to 6-fold, like a wild molecular highlighter.

Monday, July 30, 2012

"Pure Goodness" - Whirlpool's Chemophobic Water Ad

Last night, courtesy of Chemjobber, came this ridiculous sham ad interesting tidbit:
Here's the Whirlpool pop-up ad I saw that started it all: "Don't drink from the periodic table."  http://t.co/M5MBCiKf
Done chuckling yet? I hope not, because you haven't seen the accompanying video, with cloying tagline "Pure Goodness." Apparently, for Whirlpool's target market - wealthy American moms with stupendously huge kitchens - the issue of anything in drinking water scares them silly. And that's the right word, because that pop-up ad above literally reads "don't Drink from the periodic table." Did I somehow miss the memo?

News Flash! Dateline: July 30, 2012 - Water officially no longer derived from hydrogen, oxygen; sources say it exists in new 'drink dimension,' far removed from natural world!

OK, I get it: filtering water removes certain trace metals and organic products you might not want to ordinarily consume - for the moment, we'll overlook fluoride, sodium salts, or relatively innocuous trace metals like iron and copper. If you believe the ad, every poured cup of tap water contains the following (~ 0:09 in the video): mercury, chlorine, lead, ethylbenzene, ortho-dichlorobenzene, lindane, atrazine, para-dichlorobenzene, endrin, MTBE, and benzene. Nevermind that two of the listed pesticides (lindane, endrin) are long-since banned from food crops, or that local water authorities test for most of the other potential contaminants.

What about those scary-looking chemical structures at 0:05? (see left). I checked 'em out: from left, moving clockwise, you have carbofuran, dinoseb, and alachlor (Picky pedagogical note: I've never seen a gem-dimethyl group drawn that way before...should I expect some sort of agostic bond?). Dinoseb and carbofuran are both banned pesticides, and alachlor, though common, lists as only a Class III (slightly toxic) toxin.

As with all chemophobic ads, realize that Whirlpool exaggerates the situation to sell more fancy refrigerators. The same effect can be achieved with any carbon filter: remember Pur, or Brita? Perhaps then you wouldn't have to worry about the other pressing concern (0:58)...

...deadly fridge fungus!
"Everyone run, it's got Timmy!"
Credit: whirlpool YouTube

Wednesday, July 25, 2012

Great Expectations for 'Metal-Free' Reactions

Reading through some recent "metal-free" coupling literature, I came across a fantastic footnote. Check out the lengths chemists Carsten Bolm and Isabelle Thomé have to go to in order to certify their latest reaction:
"(16) Great care was taken to avoid the presence of transition metal impurities. All starting materials were synthesized without using any transition metal...reagent transfers were performed with one-way plastic spatulas, and new glassware and stirbars were used for the cyclization reactions. The starting materials and reagents were analyzed to the detection limit of 4 ppb by atomic absorption spectroscopy (AAS) or inductively coupled mass spectrometry (ICP-MS).
Data [for a representative intermediate] - Cu < 4ppb, Pd <4 ppb; Kcarb - Cu < 4 ppb, Pd < 4 ppb; DMEDA [ligand] - Cu 2.4 ppm, Pd < 4 ppb." [Emphasis mine]
Sand - Probably > 4ppb "active" metals!
Source: 123RF

I'll be honest with you, I've never tested for metals in my starting materials below ~1 ppm (Food for thought: here's an EMA document detailing allowable catalyst residue in human medicines).  I'd wager that 99.9% of workaday bench chemists haven't, either. 

Bolm's group endures this rigor because, well, they literally wrote the book on trace metal catalysis. Quite honestly, I'd bet that they felt a bit uneasy when they measured the DMEDA copper concentration; more than a few of these "metal-free" reactions proceed with vanishingly small amounts of catalyst.

Tuesday, July 24, 2012

Now Where Have I Heard This Before?

Yesterday morning, I heard an NPR report that detailed more strife in a typically white-collar profession. Whose field do you suppose we're discussing?
"...schools routinely said that 90 percent or more of their graduates had jobs nine months after graduation. It turns out they were including barista positions, low-level marketing gigs, or just about anything else you could call a job." [Emphasis mine]
"At some schools, less than a third of their graduating class were obtaining long-term, full-time jobs" 
"A new study reveals that since 2009, the median starting salary...has fallen 35 percent." 
Any more of these posts, and I might
have to rename the blog!
Credit: Arrested Development
Give up? It's not chemists, it's lawyers (This story does seem to spring eternal, given earlier posts by Chemjobber and myself). The comparison's just too apt to pass up: young grads consider financial security, invest their time towards an advanced degree, and later awaken to an economy facing a glut of overeducated professionals.

To their credit, at least the American Bar Association (ABA) seems aware of the risk, and wants to inform newly-admitted legal students of the economic dangers. Their Nero, unlike ours, isn't fiddling while Rome burns. So, what lessons could Ph.D.-granting chemistry departments learn from the legal profession? 

Honesty - Brian Vastag's Washington Post article from two weeks ago really struck a chord, amassing nearly 3700 comments and prompting discussion up and down the blogosphere. Although it's a political talking point (STEM STEM STEM!), chemical graduate departments must take a page from the ABA and inform new recruits that the salad days of secure scientific employment have passed.

Transparency - As Janet Stemwedel recently mused: What does a chemistry Ph.D. get you? Are alternative careers really playing out? How are pharma salaries adjusting to the recession? Are stock options, benefits, or retirement plans really going away? Where will the jobs be in 10 years?

CJ's correct to call for career tracking; after all, we have the technology! Through a combination of email surveys, social network mining, digital IDs, online CVs, and employer reporting, we should be able to paint a more complete picture of the sci-employment landscape. Using data from past students, new grads could adequately prepare themselves, and younger students could better assess their decision to attend grad school.

Tuesday, July 17, 2012

Curious Collaborations

Tried telecommuting? It's tough when you're bench-bound, since you can't really catalyze by cell phone, or take HPLC by HTTP. Of course, research takes strange twists and turns all the time: witness the schism between compound "designers" and "makers" in Pfizer's geographically divided new organization

Long-distance scientific collaboration crops up in all sorts of interesting places. Creative minds always find a way, albeit leaning heavily on technology to help smooth things out. Here's a few interesting examples:

Physics by Ham Radio (1950) - While on sabbatical in Brazil, Richard Feynman continued his Caltech research by hooking up with a pirate ham radio operator.
"I found an amateur radio operator in Brazil, [but] because there was something slightly illegal about it, he'd give me some call letters...So I'd say 'This is WKWX. Could you please tell me the spacing between the certain levels in boron we talked about last week?"
Source:Brian Dettmer, 2008
Thanks to Chemjobber for pointing this out!
Manuscript Writing by Phone, Post, and Boat (1969) -  Writing in How the Hippies Saved Physics (p. 47), author David Kaiser describes how two authors - Abner Shimony and John Clauser - tackled paper submissions from afar. While writing their first quantum mechanics manuscript, Clauser decided to sail down the East coast, towards an eventual postdoc at Berkeley. Here's how it went:
" ...each time Clauser sailed into a port along the East Coast, he would find a telephone and check in with Shimony...then Shimony would mail copies of the edited draft to every marina in the next city on Clauser's itinerary, 'some of which I picked up,' Clauser explained, "and some of which are probably still waiting there for all I know.'"
SPARC (1992) - The Space Physics and Aeronomy Research Collaboratory, first established at the University of Michigan, grew over the next 6 years to include several worldwide radio telescopes. The project now incorporates behavioral scientists, computer programmers, physicists, and astronomers, who "...sit down to their computers in the comfort of their offices and call up a screen that allows them to control and gather data from more than a dozen instruments located around--and above--the globe." Online collaborative tools developed by this consortium include Java programs, chat rooms, and a digital whiteboard.

Instant Messaging, Liveblogging, Wikis (mid-2000s) - Regular readers recall the recent uptick in live-blogging, that is, conducting a live experiment while posting data, observations, and commentary. Paul at Tot Syn famously debunked NaH oxidation, and Azmanam proved that LemiShine cleaner contains citric acid. The open science movement brings together scientists from around the globe to live-edit papers on electronic documents called wikis. My biggest surprise? Digging up an IEEE abstract on eChemIM. Apparently, it's a real-time application that allows exchange of structures and protein sequences through a simple pop-up window. Sounds like a cool new way to collaborate!

Readers, have I left out your favorite way to connect? Let me know in the comments.

Sunday, July 15, 2012

JLC Turns One!

Alitta virens (sandworm)
Credit: A. Semenov, White Sea Biological Station
Heartfelt thanks go out to each and every person who clicked over here in the past 366 days (leap year!).

No new post today; I'm going to take the day off to celebrate. How does one celebrate a blog's birthday? Maybe an ice cream cone with a candle stuck in the top, or a cupcake with a sparkler?

Here's a few salient factoids from my first year "full-time."

Year One Stats:
Total Pageviews: 74,000+
Total Posts: 125
Tweets: 3,414
Blog Carnivals: 2

Total Time Blogging: 500 h, ~6% of the last year.

Posts Elsewhere*: The Haystack (26), Chemistry Blog (4),  Chemjobber (3), Totally Synthetic (2), Sci Am (2), Newscripts (2). 
(*May 2011 - July 2012. Want a guest post, or want to guest post? Email me at seearroh_AT_gmail_DOT_com)

Recurring Themes: Chemophobia, Skepticism, Cartoons, Space Dinos, Arsenic Life, Structure Mishaps, Food Chemistry, Catalysis, Pop Culture Chemistry, Blog Philosophy, Arts & Crafts

Thursday, July 12, 2012

Friday Fun - WWWTP, Cartoons!

Anyone out there watch Adventure Time? The animated show, currently airing on Cartoon Network, follows the adventures of a boy and his talking dog in the magical Land of Ooo.

(Bear with me, I've only seen this episode)
Source: Cartoon Network
While flipping through the channels, I happened to land on a rather new episode, called "Goliad." It involves one of the main characters - a synthetic biologist? - spawning a giant pink Sphinx from a mixture of DNA, 'chemicals,' chalk dust, and an old tooth. But that's not what caught my eye: check out the prop chalkboards set up in the "lab" - those are resonance structures on there!

(Ironically, though the characters understand electron movement for the carbonate anion, and can apparently clone life forms, the resonance structure for benzene escapes them. But, hey, this adventure occurs in a castle shaped like a wedding cake, so...caveat lector)

Everything's bigger in Texas.
One tiny problem: this chemistry know-how seems to disappear between takes. Here's another clip from the same episode, where the previously-correct carbonate has mysteriously grown another bond.

Most kids watching this will just gloss over it, assuming some mad-scientist gobbledygook. But, those of us in the WWWTP camp just can't help ourselves.

Happy Friday! Go watch some (scientifically accurate) cartoons!

BPA-Affected Mating? Something's Fishy...

The hot scientific story this week comes courtesy of the University of Minnesota: fish exposed to bisphenol-A (BPA) exhibit diminished sex traits, which leads to aberrant mating behaviors (Check out the original paper by Ward and Blum, or for a more plain-English rundown, try Science Sushi over at SciAm Blogs).

Blacktail shiner, C. venusta
Source: Futurity.org
I've held off on writing about BPA for a long time; it's like a science journalism black hole, dense with conflicting data, politics, and social issues. But I had to weigh in here, because no other outlet seems to have shown proper skepticism, or asked the right questions.

1. Dose - The authors of a 2012 Endocrine Reviews article on low-dose endocrine disruptors point out (p. 18) that the EPA extrapolated reference dose for BPA in humans = 50 ug / kg body weight (Update, 7/12/12 - Check the comments for a more applicable animal toxicity value). That means, according to them, that you could eat a few specks of it with dinner every day for the rest of your life, and suffer no ill effects.

So what does this have to do with the fish paper? Note the dose (p.3): 1280 ug / L. Do the math: 1L of water = 1000 mL, density of water (room temp) = 1 g / mL, thus 1L = 1 kg. How much does a fish weigh, a few grams at most? This study overdoses them by at least a few orders of magnitude. Pardon the pun, but these little guys are literally swimming in BPA. Furthermore, the scientists change out the tank water every 24 hours, so the fish are certainly overexposed relative to their control brethren.

2. Cosolvent Effects - BPA has relatively low water solubility, so the authors dissolve it into their mixture with a cosolvent, triethylene glycol. Well, that's fine, as long as they run the control - water with triethylene glycol and no BPA - which they have. So, what happened? The female fish studied show no appreciable difference (Table 1) between straight H2O and cosolvent-H2O mixtures. Pity the poor blacktail shiner (C. venusta) males, though: they show marked dropoffs in all courtship metrics from cosolvent control water alone! (No BPA added). This data point does not merit discussion in the paper, however.

3. Standard Environment - Coloration and mating behavior definitely both suffer when we lock fish in tanks bombarded with BPA. But what about in the wild? How much BPA do these fish encounter in their native river habitats? Anywhere near these concentrations? Do wild fish caught on-site exhibit these same color losses? Is BPA exposure the sole factor influencing interspecies hybridization?

Readers, I'm no evolutionary biologist, so please set me straight on a few of these points. To clarify, I don't deny that xenobiotics (atrazine, estradiol) can affect marine life, but this particular study seems somewhat subject to interpretation - a scientific 'fish story.'

Tuesday, July 10, 2012

MacMillan's Latest - Almost Autocatalysis?

There's been a veritable treasure trove of interesting reactions in JACS over the past month. One particular ASAP caught my eye today: the latest SOMO-organocatalysis reaction from the MacMillan group at Princeton University.

Back up a second, SOMO? Organocatalysis? For those readers normally not nose-first in organic journals, I'll explain a little. SOMO stands for singly-occupied molecular orbital, which means there's radical chemistry afoot! The initial intermediate in many of these reactions, an enamine, reacts with a single-electron oxidant to form a radical cation, which functions as a sort of chiral radical nucleophile...a rare duck.

Future Organocatalyst?
Pyrrolidine Power!
Organocatalysis utilizes small molecules - amines, urea derivatives, hydrogen-bond donors, or small peptides - to accelerate chemical reactions. MacMillan himself gives a good short course on the topic. Organocatalysis bridges the synthetic and biochemical worlds, adapting Nature's enzymatic tricks into new reactivity.

So, why highlight this reaction? Ever since the Soai reaction, a zinc-catalyzed alkylation first reported in 1995, chemists have been enthralled with autocatalysis, the idea that the product of a given reaction could serve as its own catalyst. In theory, you could start with a tiny bit of an (almost) racemic catalyst, and wind up with a fast, highly selective reaction.

Note the similarity between the catalyst (a pyrrolidinone) and the product (a pyrrolidine). Clip off the nosyl protecting group, and I'd believe that product capable of catalyzing its own formation. Now, I'm not usually a betting person, but I like to look skeptically for what's not mentioned. In this case, only two of the products exhibit the same 2,5 substitution as the catalysts, and the authors mention catalyst development only indirectly. 

I'll offer anyone 3:1 odds that, in the next year, an autocatalytic version of this reaction pops up.

Monday, July 9, 2012

Chemophobia, Vacation Style

While eating at a neighborhood breakfast nook this weekend, the owner came out to inquire about our food. Tasty, hot enough? The normal grunts and nods of approval followed. The owner then took great pains to mention my better half's egg-white omelette. A direct quote:
"All freshly-made egg whites. I never let Egg Beaters in my kitchen. Too many chemicals."
The 'chemical-free' egg, made
entirely from unicorn horn,
 thought energy, and pixie wings
I sat on my hands, pursed my lips, and fought back the urge to autocorrect. Ahh, the well-worn 'chemicals-in-food' trope, rearing its ugly head over Sunday breakfast.

Later on, I did what any chemist would, and found the Egg Beaters ingredients list online. Surprisingly difficult! The E.B. corporate site dodges and darts, so I went to a "healthy-kitchen" blog instead...bingo! Suffice to say, you know the outcome already: there's chemicals in there, by golly! Just like in flowers, dirt, engine oil, coral, or a humble glass of water. Actually, I was surprised that the ingredients were so innocuous:

Egg Whites, Less than 1%: Natural Flavor, Color (Includes Beta Carotene), Spices, Salt, Onion Powder, Vegetable Gums (Xanthan Gum, Guar Gum), Maltodextrin. Vitamins and Minerals: Calcium Sulfate, Iron (Ferric Phosphate), Vitamin E (Alpha Tocopherol Acetate), Zinc Sulfate, Calcium Pantothenate, Vitamin B12, Vitamin B2 (Riboflavin), Vitamin B1 (Thiamine Mononitrate), Vitamin B6 (Pyridoxine Hydrochloride), Folic Acid, Biotin, Vitamin D3   [credit: Erin Coates, The Healthy Apron]

So, that's two naturally-derived gums, a natural dye, a starch, and a bunch of vitamins and minerals you'd've encountered in the Minute Maid juices the restaurant also served (Nevermind the CoffeeMate creamers, or the artificial sweetener!).

Ignorance is bliss.

Wednesday, July 4, 2012

Head-Scratching "Sanros" Structures

It's like a crossword puzzle...
Source: Chemistry World
Over at Chemistry World, Duncan Browne posted a review of a new applet version of the Kurti / Czako book Strategic Applications of Named Reactions in Organic Synthesis (for the hip iPhone crowd, the title has been condensed to simply "Sanros"). The trial version allows access to 25 out of the 250 reactions included in paid access. I'm all for chemistry-enabled free software making its way out into the public.

Just one tiny problem: what the heck is that structure? Maybe the atoms were inadverently deleted in transit, or perhaps it's meant as an artistic statement? I can't imagine this molecular graphic falls under Elsevier copyright protection.

In a way, it's like a detective mystery: can you infer what's missing? I took a crack at it myself (see below). I figured the structure on the right was either a dithiane (S,S) or ketal (O,O). The bottom ring could have any combination of N,O,S, so we'll swap in a morpholine. The aromatic? Gotta be a pyridine. Uh-oh, there could be anything terminating those 'short' bonds on the cyclopentane, or on the alpha bonds stemming below the cyclopropane. I'll just infer methyl groups, for now.

Of course, without knowing the actual natural product, and without access to database software due to the holiday, I have no way to know if I'm barking up the right tree. Anyone care to help?

Happy Fourth of July, everyone!

Update, 7/4/12 - Commenter @azmanam wins the platinum coin for his search efforts, locating the correct intermediate from a Boger total synthesis (see below). So, in the end, I went 4 for 9 on "mystery atoms!"

Higgs Mania - Any Chem Headlines Worth 'Camping Out' For?

In case you've been traveling - or living in the woods with limited 'net access - you may have heard that a massive press conference will be staged in Switzerland in just a few hours already happened. Speculation runs rampant, but many believe that CERN researchers may finally announce their "5-sigma-certified" confirmation of the Higgs boson, the mysterious missing link in the physics Standard Model. The whole thing's taken on a rather rock-concert feel, as evidenced by this tweet, from particle physics blogger Jester:
"Higgs seminar kicks off 9am but people queuing to auditorium from midnight. Now it's about 100 people waiting in front of closed door"
"Dude, artificial photosynthesis?!? We have to be there!"
Source: Patrik Giardino | evolve
(The author even runs a New Year's Eve-style counter on the site, reading Higgs Discovery in...)

So, I thought back to Philip Ball's prescient 2011 "Chemistry Grand Challenges" list for inspiration. What kind of chemistry headline would be so amazing that you'd be willing to camp outside the building for 9 hours?

"Human Brain Chemically Mapped; New,  Targeted Drug Cures Blindness, Alzheimer's, Dementia in Single Easy-to-Swallow Gelcap."

"Artificial Photosynthesis Shatters Expectations: Up to 10% Efficiency...and Guess What? It's Iron-Based!"

"SETI Detects Space Dinos in Faraway Galaxy; Opposite Life Chirality Confirmed. Defense Dept. Consults with Preeminent Paleontologists."

"Cosmochemistry Made Easy: Harness the Power of Cold Fusion for your Fireplace!"

"Quantum Computer Outraces Google PageRank for Search Speeds....and Guess What? It's Iron-Based!"

Update, 7/4/12 - Looks like 5-sigma results are in, according to multiple news sites. Houston, we (probably) have Higgs!

Tuesday, July 3, 2012

Plant Papers, Springing Up in Science

"Filter flower"
If you look around the literature lately, biosynthesis and plant metabolism reviews seem to be cropping up everywhere. The latest batch, out in Science just last week, explore several key concepts for those not yet tangled up in Vinca's vines, or dreaming of Papaver's poppies. Ten different papers discuss topics as diverse as alkaloid gene clusters, soil nutrient incorporation, metabolic diversity, medicinal compound mining, and how tomato color impacts taste.

Spend a few minutes reading through, and hopefully come away with a greater appreciation for plants - the original medicinal chemists!

Cyclophanes Fall Apart for Rhodium

When chemists design syntheses, they usually think in terms of building up, not tearing down. We alkylate, we esterify, we cyclize, adding always more molecular weight, joining synthons together. Occasionally, bonds must be broken. Considering most protecting groups, severing C-N, C-O, and C-X bonds keeps chemists of all stripes pretty busy. What about C-C scission? Not so much.

Sure, there's your decarboxylations, your ozonolyses, your samarium iodide reductions. Long ago, natural enzymes figured out how to push electron density around to slice up substrates: think about gramine fragmentation, Poitier oxidation, or the (now-defunct) Pictet-Spengler spiro mechanism. But you don't often see fully saturated sp3 carbon-carbon bonds falling apart; after all, we'd be dealing biology a mortal blow with such precarious engineering. 

Wouldn't it be cool, though, if we could just add a specific catalyst, a dash of water, and selectively crack a hydrocarbon?
I don't recall seeing this graphic in the SI...but I can hope.
Turns out you can...if the system's just right. Chinese University of Hong Kong chemistry professor Kin Shing Chan, with coworkers Ching Tat To and Kwong Shing Choi, reported just such a reaction in JACS ASAP yesterday. The scientists mix some Rh(III) porphyrin, some base, and a 100-fold excess of water, heating everything in the dark for 2-3 days. Out pops the "bibenzyl" compound (83%), which initially causes a bit of head-scratching: why don't they see C-H activation products? And where's the hydrogen coming from? 


There's quite a bit of C-H activation, actually - it just doesn't go anywhere under the conditions. Swapping in deuterium oxide leads, unsurprisingly, to "D" incorporation on all the methylene groups and at the two newly-formed methyl groups. So the water indeed provides hydrogen, but not the way we'd usually think about it. No water splitting, no hydride formation, no "M-H." Instead, it's simply a radical quench: each metal-carbon bond, formed from C-C bond homolysis, grabs an "H-dot" from a neighboring water, and the remaining OH radicals shuffle away to produce hydrogen peroxide. And the rate looks pretty screwy, with second-order kinetics in metal, which the authors think means that two separate Rh(II) radical species - from Rh(III) reduction in situ - cooperate to cleave each side of the C-C bond simultaneously.
Source: Chan et. al., JACS ASAP 2012
Well, enough hype: only a few substrates (cyclooctane, cyclophane, strained substrates) have been shown to reliably react with these rhodium porphyrins, and the conditions (200 degrees Celsius, 3-4 days, in the dark?!?) aren't winning any immediate med chem converts. Hey, these things take a little time to become practical, so maybe one day you'll reach for your C-C "knife" of choice, and dial-in your molecular dissection.