Review: ChemDraw on the iPad

Note: For the purposes of this review, PerkinElmer provided me with a copy of ChemDraw for iPad (SL). I already owned a copy of the standard version, but many of the features that are most relevant to my chemistry are currently in the site license version. These features will eventually be in the version on the App Store. That said, I received no financial recompense, nor has PerkinElmer had any input in this review, other than Philip Skinner responding to my pestering questions via Flick-to-Share.

Chemdraw for iPad ($10 in the App Store, available for free via many departmental site licenses):

Pros: Easy to use, versatile, fast; sharing options are robust and easy to use; interfaces well with the desktop app

Cons: Sometimes crashes on older iPads; missing the tools that would be needed to make polished figures for a paper; interfacing with desktop app requires intermediacy of email app, creating some redundancies

Recommendation: Will be of varying utility from person to person, but definitely recommended, even if just to be able to receive documents from other people. The “living documents” feature that arises from frequent use of the Flick2Share function is very useful and clever, particularly for collaborators who are geographically isolated. Luckily, the app is available free through most site licenses for the desktop app, but if you don’t have access that way, the $10 is likely well-spent.


Welcome to the future, folks. ChemDraw, the desktop computing program that took us from stencils to mouse-clicks nearly thirty years ago, is now available on iPad. I’ve had the app since it came out, but hadn’t been able to make particularly good use of it before some of the new features available on the Site License version of the app. Philip Skinner from PerkinElmer offered to give me a trial version of that version, and so a perfect opportunity for a review presented itself.

Before going further, I think it’s important to identify what this app is meant to do, as what your expectations are will dramatically affect whether you find this app to be a good investment. From the PerkinElmer website,

ChemDraw® for iPad® provides all the tools scientists need to capture and share chemical inspiration and innovation whenever they want and wherever they are. [snip] [R]esearchers can quickly sketch them with ChemDraw® for iPad® as ideas take shape and share them with colleagues and save them for later elaboration and processing.

I point all this out because I think this app is doing a phenomenal job of being ChemDraw on-the-go, despite being an imperfect figure-generator on the iPad. You are not going to make manuscript-quality figures with this app, but what you will be able to do is start them in pretty fantastic detail, share that start, and touch it up at your desk with the desktop ChemDraw.

So, to test this premise, I did exactly that–for the past month or so, whenever I knew I had a document that was going to be needed later in the day, I tried to start it on my bus ride to work and transfer it to my desk for final touch-ups. In addition, I tried to use it as an idea repository, something that I normally do in a notebook, or in digital form like this:

IMG_0268

While that is useful to me, it isn’t necessarily inherently obvious to the intended recipient. However, CD for iPad let me send this instead:

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Much better, right? Moreover, that “share” button in the top left lets you peg it to your intended recipient in PDF, PNG, or CDXML format, even if that recipient is your own email. Obviously, the “export via email to CDXML” function is the single most useful thing about this, though I wish there was some integration with the desktop app so that you might be able to send it over directly, similar to the manner in how the Papers app by Mekentosj syncs PDFs once you get onto the same WiFi network as your computer with the desktop app. For now, though, this is orders of magnitude better than scrawling in a notebook, or even using a stylus-based app on an iPad.

That is, of course, assuming that drawing structures is fast and easy. While I can’t draw structures as quickly on the iPad as I can on the desktop (there are a lot of shortcuts that just aren’t possible on the touch interface, sadly), I will say that it’s as fast, often faster, and infinitely more legible than on a pad of paper or drawing app, particularly on bumpy Illinois roads. Rather than simply describe it, I went ahead and recreated a figure from one of my recent papers in the iPad app to show you what it looks like.

IMG_0258

Upon opening the app, you’re greeted with the above screen. On the right you have your drawing and manipulation tools, and the top you have your document creation, sharing, and manipulation tools. It’s all very clean and the buttons are easy to hit, even with big fingers like mine. Drawing is a breeze, and manipulating the resulting structures just takes a bit of playing with the selection tools. Pro-tip: for the selection, you can’t just touch a nucleus and start dragging; you have to deliberately select, move, then deselect each nucleus. It takes a little getting used to, but it actually ends up preventing more annoyance via fat-fingers than anything else.

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Once you’ve put down a few structures and typed out some captions, you might not notice that the “chemical formula” mode is not the default, and so enabling it just requires you to select the text and use the little palette tool to enable it, as shown in the image above. Here you can also change the color of a caption; sadly, it changes the entire caption’s color, not letting me get my advisor’s trademark color-coding of various nuclei. After a little bit of tweaking, I arrived at this:

IMG_0261

Which I then used the share pane to send to myself, yielding this in CD14:

on desktop

It’s strange that it put the structures there on the page, but if this is what I had in hand upon arriving to work, I could have a workable figure in 30 seconds. What’s notably missing from the app (as far as I can tell) are alignment tools, distribution tools, and selective coloring. Again, as a tool for on-the-go, that’s totally fine, but it won’t replace your computer when the time comes to put the manuscript together.

So, what else is of note? Well, for one, organometallics, particularly metallocenes, are enormously easier to draw.

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IMG_0264 IMG_0263

Stamping down a ferrocene is easy, then adding on nuclei takes just a few taps of the very colorful and fun periodic table picker. Yes, those are phosphorous-34 nuclei, because why not–tapping the P repeatedly cycles through its various isotopes, even the crazy ones, which I love. One complaint: you can’t pick the heaviest elements. C’mon, guys, how hard would it have been to let me sketch an imaginary Uut complex? ;-) These metallocenes are pretty easy to decorate, but if you want their eclipsed orientations (I may well be the only one) you’re out of luck. Again, save it for the desktop tweaks.

Making metal complexes from these is pretty straightforward, but you would do well to turn off “valence errors” and “misc. errors,” as shown below, because these show up all the time in metal complex drawings, but here they make it difficult to see the nuclei in question. While they’re just annoying in the desktop version, they’re detrimental here, so just turn them off if you’re an inorganicker.

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I went ahead and sketched the laughable molecule shown here, and discovered that there isn’t a way to control the point of attachment of templates added to existing structures, so if you want them to connect anywhere but at the default, draw them separately, add the bond, then use “clean up” at the top to make it look nice again.

All told, it took maybe a minute and a half to make this picture, so I figured it was time to send it:

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You see some of the standard options there, but worth mentioning here, specifically, are:

Flick2Share: This feature is awesome; using your PerkinElmer account, you can tap through your contacts and literally just swipe up to send them the file. It arrives on their end fully editable, savable, etc. I had a great time with this, pegging questions to Philip, who could show me what to do right in the file (thanks, Philip!) and swapping notes with collaborators, wherein we tracked the progress of a synthesis by passing the file back and forth with annotations. Smooth as can be, and potentially very useful in the classroom. I’ll try to update with some pictures of this in action soon.

Moxtra Meet: This is a feature that is really nice, but doesn’t play well with my older iPad. It’s essentially a Google Hangout that lets you all share a cast Chemdraw screen. I didn’t get a lot of time to play with it before it crashed on my original iPad Mini, but it’s a great idea at least, given that Go2Meeting and such restrict you just to Safari for web meetings.

So, there you have it. As a brainstorming app, ChemDraw for iPad is phenomenal. As a way to scribble down and idea and use it to then make a figure, send it to a colleague, and collaborate is something that I am very much in favor of. It isn’t a replacement for the desktop app, but I don’t think it was meant to be. The app is user-friendly and stable (a few crashes on my iPad Mini, but the app reloaded my work-in-progress perfectly every time), and definitely worth $10 if you’re the type to get ideas at any time and need ways to make sure they get down and would like to see them then get out to other people in your group.

What’s with aminoquinoline directing groups all of a sudden?

Seriously, did someone start giving 8-aminoquinoline away for free?

 aminoquinoline

I started noticing a particular trend in the ASAPs of some of the organic journals I follow, all involving various uses of the aminoquinoline amide as a directing group. The number of papers to come out in the past month or so is absolutely staggering, and why not–the results are some really cool reactions! The one that first caught my attention was actually published back-to-back by both Silas Cook1 (Indiana) and Nakamura2 (U. Tokyo):

 aminoquinoline 1

As far as alkylation reactions go, this one hits a lot of the points on the “want” list—highly selective, uses a non-precious metal, doesn’t require ludicrous temperatures, and is done very, very quickly. But again, two groups simultaneously discovered nearly identical reactions—something must have been going on to make this happen, especially since these directed reactions have continued to inspire new variants even in the month following their publication. Assuming that these folks took longer than a week or two to put together their reactions, all of these groups must have been working on this at the same time! What started this trend? 

Well, there has definitely been plenty of literature on the use of aminoquinoline directing groups. In recent years, it has been used to direct copper-catalyzed alkynylation,3 etherification,4 fluorination,5 arylation,6 and sulfenylation7; iron-catalyzed alkylation,1,2,8 allylation,9 and amination10; nickel-catalyzed alkylation11; and a whole slew of palladium-catalyzed functionalization reactions12-17. This, of course, only covers the aryl amides in the literature, and all of them are perfectly ortho-selective.

 aminoquinoline 2

Daugulis and coworkers first showed this directing effect in 2005,12 where the appropriate size of the N^N chelate was demonstrated with picolinamides and aminoquinoline amides. It turns out that a two sp2 carbon bridge is a sweet spot for these complexes, especially for Pd(II), which is stabilized by the anionic amide ligand.

 aminoquinoline 3

It’s worth noting that in the large majority of these cases, the reactions in hand are reactions that don’t rely on the quinoline to work; instead, they merely take advantage of the arrangement of the substrate being bound in a bidentate fashion to lower the barrier to activating the ortho proton specifically. Some of these reactions proceed through single electron mechanisms, others via two-electron processes, but in all cases the ortho proton stares the metal in the face and is activated preferentially over the others simply as a result of proximity. More than that, however, it also appears to cut down on bimetallic processes—because the ligand is the substrate (or the other way around, depending on your perspective), each reactive metal center is always entropically poised to engage in the monometallic mechanism, which may otherwise may not be true, particularly of iron chemistry, where homodimerization is a common side reaction.

In fact, it might be just this last point that inspired the most recent deluge of chemistry on the subject. It’s worth noting that nearly every aminoquinoline-directed reaction published this summer featured iron catalysis, and I doubt that’s a coincidence. Earlier this year, Chatani and co-workers published a paper that described an unusually strong electronic effect in the ruthenium-catalyzed arylation of these compounds18 (see the paper for some beautiful Hammett studies). Between the entropic sequestration of the substrate coupled with enhanced substituent effects, it makes perfect sense to use these substrates to “tame” iron catalysts, which are notorious for having non-selective or off-target reactivity, especially in alkylation reactions. Indeed, despite being pigeon-holed into benzoic acid derivatives, these are by far some of the most selective iron-mediated alkylations in the literature, and I fully expect this principle to be expanded upon in great detail in future applications of first-row metals in catalysis.

Is there anything else that is particularly cool here, though? I think so—it turns out that these aminoquinoline amides are remarkable in field strength and coordination environment to the iron-containing active site of nitrile hydratase, and some of the better models for it actually use ligands that have exactly this motif.19 Especially with respect to Chatani’s electronic effects, I wonder if the electronic parameters of these reactions and their selectivity toward small molecule substrates have any implications for the mechanism of the metalloenzyme or related biomolecules. That would certainly be a different take on things, with catalysis informing biochemistry, rather than the reverse!

  1. Fruchey, E. R., Monks, B. M. & Cook, S. P. A Unified Strategy for Iron-Catalyzed ortho-Alkylation of Carboxamides. J. Am. Chem. Soc. (2014). doi:10.1021/ja506823u
  2. Ilies, L., Matsubara, T., Ichikawa, S., Asako, S. & Nakamura, E. Iron-Catalyzed Directed Alkylation of Aromatic and Olefinic Carboxamides with Primary and Secondary Alkyl Tosylates, Mesylates, and Halides. J. Am. Chem. Soc. (2014). doi:10.1021/ja5066015
  3. Dong, J., Wang, F. & You, J. Copper-mediated tandem oxidative C(sp2)-H/C(sp)-H alkynylation and annulation of arenes with terminal alkynes. Org. Lett. 16, 2884–2887 (2014).
  4. Roane, J. & Daugulis, O. Copper-catalyzed etherification of arene C-H bonds. Org. Lett. 15, 5842–5845 (2013).
  5. Truong, T., Klimovica, K. & Daugulis, O. Copper-catalyzed, directing group-assisted fluorination of arene and heteroarene C-H bonds. J. Am. Chem. Soc. 135, 9342–9345 (2013).
  6. Nishino, M., Hirano, K., Satoh, T. & Miura, M. Copper-mediated C-H/C-H biaryl coupling of benzoic acid derivatives and 1,3-azoles. Angew. Chem. Int. Ed. Engl. 52, 4457–4461 (2013).
  7. Tran, L. D., Popov, I. & Daugulis, O. Copper-promoted sulfenylation of sp2 C-H bonds. J. Am. Chem. Soc. 134, 18237–18240 (2012).
  8. Monks, B. M., Fruchey, E. R. & Cook, S. P. Iron-Catalyzed C(sp(2) )-H Alkylation of Carboxamides with Primary Electrophiles. Angew. Chem. Int. Ed. Engl. (2014). doi:10.1002/anie.201406594
  9. Asako, S., Ilies, L. & Nakamura, E. Iron-catalyzed ortho-allylation of aromatic carboxamides with allyl ethers. J. Am. Chem. Soc. 135, 17755–17757 (2013).
  10. Matsubara, T., Asako, S., Ilies, L. & Nakamura, E. Synthesis of anthranilic acid derivatives through iron-catalyzed ortho amination of aromatic carboxamides with N-chloroamines. J. Am. Chem. Soc. 136, 646–649 (2014).
  11. Aihara, Y. & Chatani, N. Nickel-catalyzed direct alkylation of C-H bonds in benzamides and acrylamides with functionalized alkyl halides via bidentate-chelation assistance. J. Am. Chem. Soc. 135, 5308–5311 (2013).
  12. Zaitsev, V. G., Shabashov, D. & Daugulis, O. Highly regioselective arylation of sp3 C-H bonds catalyzed by palladium acetate. J. Am. Chem. Soc. 127, 13154–13155 (2005).
  13. Gou, F.-R. et al. Palladium-catalyzed aryl C-H bonds activation/acetoxylation utilizing a bidentate system. Org. Lett. 11, 5726–5729 (2009).
  14. Shabashov, D. & Daugulis, O. Auxiliary-assisted palladium-catalyzed arylation and alkylation of sp2 and sp3 carbon-hydrogen bonds. J. Am. Chem. Soc. 132, 3965–3972 (2010).
  15. Ano, Y., Tobisu, M. & Chatani, N. Palladium-catalyzed direct ortho-alkynylation of aromatic carboxylic acid derivatives. Org. Lett. 14, 354–357 (2012).
  16. Nadres, E. T., Santos, G. I. F., Shabashov, D. & Daugulis, O. Scope and limitations of auxiliary-assisted, palladium-catalyzed arylation and alkylation of sp2 and sp3 C-H bonds. J. Org. Chem. 78, 9689–9714 (2013).
  17. Kanyiva, K. S., Kuninobu, Y. & Kanai, M. Palladium-catalyzed direct C-H silylation and germanylation of benzamides and carboxamides. Org. Lett. 16, 1968–1971 (2014).
  18. Aihara, Y. & Chatani, N. Ruthenium-catalyzed direct arylation of C–H bonds in aromatic amides containing a bidentate directing group: significant electronic effects on arylation. Chemical Science 4, 664–670 (2013).
  19. Harrop, T. C., Olmstead, M. M. & Mascharak, P. K. Modeling the active site of nitrile hydratase: synthetic strategies to ensure simultaneous coordination of carboxamido-N and thiolato-S to Fe(III) centers. Inorg. Chem. 44, 9527–9533 (2005).

EDIT: Yet another one, a day later in JOC: http://pubs.acs.org/doi/abs/10.1021/jo501691f

Yoghurt vs Scientists

Note: This article originally appeared in Nature Chemistry as part of their Blogroll section. You can see the original post here, though nothing was changed in its republication here, save for the postscript.


 

Recent advertising strategies in which ‘anti-science’ is equated with ‘all-natural’ have rubbed some scientists the wrong way.

Yoghurt maker Chobani earned the ire of the scientific community with a slogan that appeared on the lids of their new low-calorie Greek yoghurt. Piper Klemm was the first to tweet about the controversial catchphrase: ‘Nature got us to 100 calories, not scientists. #howmatters’. Hundreds of tweets on the topic soon followed, as well as numerous blog posts by scientists decrying the belittling of science in advertising.

Writing at In the Pipeline, Derek Lowe offered a tongue-in-cheek analysis of the reason for the overwhelming response to the slogan, pointing out that despite Chobani’s desire to advertise an ‘all-natural’ product, mass-produced yoghurt requires a lot of food science. In fact, Chad Jones and John Coupland describe the chemistry involved in detail in a podcast at The Collapsed Wavefunction.

Chobani’s ‘natural vs scientific’ strategy of promoting foodstuffs isn’t new; bloggers have called out Finagle a Bagel on its ‘Bakers, not scientists’ campaign, and Whirlpool on their ‘Don’t drink from the Periodic Table’ adsPaul Bracher‘s ‘chemophobia’ archive at ChemBark offers a compilation of examples where science and chemicals are demonized by advertisers.

These discussions highlight that such marketing strategies not only cater to, but also inform the public’s paranoia surrounding the term ‘chemical’. In his piece on The Blog, Joe Schwarcz addresses the confusion of ‘chemicals’ and ‘dangerous chemicals’. Science education — and communication — at all levels has never been more important than the present, where terms like ‘GMO’, ‘GIF’ and ‘chemical’ are misunderstood and feared as a result. It’s now time for the chemistry community to use these events as learning and teaching opportunities.

 

P.S. Following the publication of this article, Chobani sent me a hand-written card that thanked me for “sticking with [them]” and included a coupon for free yoghurt, which I have not yet collected. While I am not a vehement Chobani-hater (their intentions were misguided, not evil), I’d like to say for the record that I’m not on their side in the matter, either.

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Scrunchers vs Punchers

As many of you may know, I love my glovebox. If you haven’t been able to experience the magic of doing a dump-and-stir Grignard reaction (with quantitatively pure arylmagnesium bromide, weighed out as a lovely crystalline material), you should absolutely consider borrowing your nearest metal-friendly neighbor’s box and having a go. You might never go back to the Schlenck line again.

Intentional hyperbole aside, when I was training my newest undergraduate researcher, we came upon the most intriguing of trends. You see, when I go into the glovebox, I “punch” my way in; that is, I use an uppercutting motion and put my entire arm in at once (barring a glove that is sticking for some reason, usually a result of the gloves having been used by a person with smaller hands earlier in the day). I taught this method to my undergraduate, who agreed that it was an effective way to get into the glove.

Later, though, a coworker took notice and told him, “You know, it’s way easier to just put each arm in a little bit, scrunch it down over the rest of your arm, and then go the rest of the way.” Later, in confidence, the undergraduate confided in me that, though he tried it for our coworker’s sake, it wasn’t an especially comfortable way to get into the box.

I got to thinking about it more and more, and noticed that there was a mix of methods in our lab for entering the glovebox; there were the Scrunchers, who go in a little, adjust the glove, and then continue, and there were the Punchers, who, like me, go in all at once like Heihachi from Tekken. Moreover, there was a distinct correlation with how long one’s arms are and one’s propensity to punch or scrunch. I am on the lower end of the puncher spread, with an arm length of 27.5″ from shoulder to fingertip, and a brief survey of my lab members and some random members of other groups in the department revealed that everyone surveyed with an arm length qualitatively less than that (I didn’t bring a ruler, just my arms) would scrunch instead.

I am interested in whether or not this is a general phenomenon. Readers, are you #TeamScruncher or #TeamPuncher? Share in the comments or on Twitter, and share your arm length if you feel so inclined!