Chemistry

There's a new paper out today in Nature on a very unusual way to determine the chirality of organic molecules. It uses an exotic effect of microwave spectroscopy, and I will immediately confess that the physics is (as of this morning, anyway) outside my range. This is going to be one of those posts that comes across as gibberish to the non-chemists in the audience. Chirality seems to be a concept that confuses people pretty rapidly, even though the examples of right and left shoes or gloves (or right and left-handed screw threads) are familiar from everyday objects, and exactly the same principles apply to molecules. But the further you dig into the concept, the trickier it gets, and when you start dragging the physics of it in, you start shedding your audience quickly. Get a dozen chemists together and ask them how, exactly, chiral compounds rotate plane-polarized light and see how that goes. (I wouldn't distinguish myself by the clarity of my explanation, either). But this paper is something else again. Here, see how you do: Here we extend this class of approaches by carrying out nonlinear resonant phase-sensitive microwave spectroscopy of gas phase samples in the presence of an adiabatically switched non-resonant orthogonal electric field; we use this technique to map the enantiomer-dependent sign of an electric dipole Rabi frequency onto the phase of emitted microwave radiation. The best I can do with this is that the two enantiomers have the same dipole moment, but that the electric field interacts with them in a manner that gives different signs. This shows up in the phase of the emitted microwaves, and (as long as the sample is cooled down, to cut back on the possible rotational states), it seems to give a very clear signal. This is a completely different way to determine chirality from the existing polarized-light ones, or the use of anomalous dispersion in X-ray data (although that one can be tricky). Here's a rundown on this new paper from Chemistry World. My guess is that this is going to be one of those techniques that will be used rarely, but when it comes up it'll be because nothing else will work at all. I also wonder if, possibly, the effect might be noticed on molecules in interstellar space under the right conditions, giving us a read on chirality from a distance?

In the previous three posts on alkynes we've introduced some new reactions that are specific to alkynes (versus alkenes): deprotonation (and subsequent substitution), partial reduction to alkenes, and the formation of aldehydes and ketones through net “hydration”. With all the focus on the ways in which alkyne chemistry can differ from alkene chemistry, it's helpful to be reminded of all the ways in which they are similar. In this post we'll go back to a key reaction mechanism pattern we observed with alkenes: the so-called, “carbocation pathway” – and explore how many of the reactions of alkenes we're familiar with can also be used with alkynes. The three major examples in this category are the reaction of hydrohalic acids (H-Cl, H-Br, and H-I) with alkynes. If you recall, when added to alkenes these reagents were attacked by the ? bond of the alkene to give a carbocation (on the most substituted carbon, giving “Markovnikov” regioselectivity) followed by attack of halide ion on the carbocation. Since alkynes merely differ from alkenes in the addition of a second ? bond, we would expect that these reactions would also work for alkynes as well – and they do! If we treat an alkyne with a single equivalent of H–Cl [note - we'll just use H-Cl in all of these examples, but HBr and HI work in exactly the same way] we end up forming an alkenyl chloride. Note that the chlorine atom ends up attached to the most substituted carbon of the alkene ["Markovnikov" regioselectivity]. Note that the product here still has a ? bond. You might be wondering if it's possible to for this ? bond to react with a second equivalent of H-Cl. The answer is yes. [Note - it is possible to just "stop" the reaction at this stage if we use just one equivalent, because the product (alkenyl chloride) is less reactive towards HCl than the starting alkyne]. Indeed, if we add a second equivalent of H-Cl, it adds to either side of the C-C ? bond, giving us the product where two chlorine atoms are on the same carbon. By the way, we call this a “geminal” dichloride (think Latin – “gemini” = twins). We can also get this product if we simply add two equivalents of H-Cl to the starting alkyne. So how might this reaction work? In a very similar fashion to how H-Cl adds to alkenes. The first step is protonation of the alkyne with H-Cl in such a manner as to give the most stable carbocation intermediate. Since carbocations are stabilized to a greater extent by electron releasing alkyl substituents than by hydrogen, the new carbocation will form at the end of the alkyne bearing the carbon substituent. In the next step, the carbocation is attacked by the chloride ion to give the alkenyl chloride. What about the second equivalent of H-Cl ? Given the fact that the geminal dichloride is the product here, the most reasonable mechanism for its formation is merely a repeat of the steps from the first reaction (as shown). However it's worth pointing out one interesting feature. Note that the carbocation in this case bears a chloride ion. Since carbocations are electron poor, and chlorine is quite an electronegative element, it's interesting to point out that the electron releasing ability of the alkyl group [and the ability of chlorine to donate a lone pair to the carbocation] “win out” here over the electron-withdrawing character of chloride ion. As mentioned above, the reactions of alkynes with HBr and HI (as well as HF, just in case you're curious) follow the exact same pathway. It's probably worth tying back this post to the post on alkenes and the carbocation pathway, noting the similarities and differences between the chemistry of alkenes and alkynes. Hopefully this table will prove useful: As with alkenes, reactions that follow this pathway proceed through a carbocation intermediate and provide the “Markovnikov” products as major. The key difference in this pathway is that hydration of alkenes gives alcohols, whereas hydration of alkynes gives carbonyl de

Scholarly literature has been virtually untouched by the digital revolution in this century. The primary communication is by digital copies of paper (PDFs) and there is little sign that it has brought any change in social structures either in Universities/Research_Establishments or in the publishing industry. The bulk of this industry comprises two sectors, commercial publishing and learned societies. The innovations have been largely restricted to Open Access publishing (pioneered by BMC and then by PLoS) and the megajournal (PLoSOne). I shall generalise, and exempt a few players from criticism: The Open Access publishers above with smaller ones such as eLife, PeerJ, MDPI, Ubiquity, etc. And a few learned societies (the International Union of Crystallography and the European Geosciences Union, and please let me have more). But in general the traditional publishers (all those not exempted) are a serious part of the problem and cannot now be part of the solution. That’s a strong statement. But over the last ten years it has been clear that publishing should change, and it hasn’t. The mainstream publishers have put energy into stopping information being disseminated and creating restrictions on how it can be used. Elsevier (documented on this list) has prevented me extracting semantic information from “their” content. The market is broken because the primary impetus to publish is increasingly driven by academic recognition rather than a desire to communicate. And this makes it impossible for publishers to act as partners in the process of creating semantics. I hear that one large publisher has now built a walled garden for content mining – you have to pay to access it and undoubtedly there are stringent conditions on its re-use. This isn’t semantic progress, it’s digital neo-colonialism. I believe that semantics arises out of community practice of the discipline. On Saturday the OKFN is having an economics hackathon (Metametrik) in London where we are taking five papers and aiming to build a semantic model. It might be in RDF, it might be in XML; the overriding principle is that it must be Open, developed in a community process. And in most disciplines this is actively resisted by the publishing community. When Wikipedia started to use Chemical Abstracts (ACS) identifiers the ACS threated Wikipedia with legal action. They backed down under community pressure. But this is no way for semantic development. It can only lead to centralised control of information. Sometimes top-down semantic development is valuable (probably essential in heavily regulated fields) but it is slow , often arbitrary and often badly engineered. We need the freedom to use the current literature and current data as our guide to creating semantics. What authors write is, in part, what they want to communicate (although the restrictions of “10 pages” is often absurd and destroys clarity and innovation). The human language contains implicit semantics, which are often much more complex that. So Metametrik will formalize the semantics of (a subset of) economic models, many of which are based on OLS (ordinary least squares). Here’s part of a typical table reporting results. It’s data so I am not asking permission to reproduce it. [It's an appalling reflection on the publication process that I should even have to, though many people are more frightened of copyright that of doing incomplete science.]   And the legend: How do we represent this table semantically? We have to identify its structure, and the individual components. The components are, for the most part well annotated in a large metadata table. (And BTW metadata is essential for reporting facts so I hope no one argues that it’s copyrightable. If they do, then scientific data in C21 is effectively paralysed.) That’s good metadata for 2001 when the paper was published. Today, however , we immediately feel the frustration o

Photoresponsive supramolecular gels that incorporate an azobenzene unit into peptide side chains are reported

The research talk and proposal talk are arguably the most important parts of the on-site interview. This post, part seven in the “Get a job, Ken! series” delves into both, as well as the final meeting with the department chair. My first piece of advice for those preparing for an on-site interview is to purchase and practice with a slide-advancing remote (a.k.a. a laser pointer or ‘clicker’). I find it tragic when a great scientist appears incompetent because they don't know how to use a borrowed clicker. It’s worthwhile owning a clicker that you know like the back of your hand. In fact, for young graduate students, I recommend investing in a clicker and practicing with it as soon as possible. I am partial to the Logitech Wireless Presenter (The author declares no competing financial interests). The Research Talk Standard seminar talks have one primary goal, to share science. Research talks during an interview have two additional goals. The first is to briefly introduce your area of research and lay a foundation for the concepts and techniques relevant to your proposal talk. This groundwork will allow for extra time during the proposal talk (vida infra) to discuss your ideas. Of course, it's important to seek a balance since not everyone who attends your proposal talk will be at the research talk, and vice versa. The second goal of the research talk is to demonstrate your teaching skills. The presentation will be open to all faculty and students—basically any involved in the hiring decision—and they’ll be asking themselves: How engaging and eloquent is this applicant? How well does he or she explain new concepts? What kind of teaching methods do they use (analogies, examples, images, etc.)? How good is she or he at answering questions? I have seen way too many talks that care more about demonstrating “I’m smart!” than actually communicating ideas. In these “I am so smart” presentations only two or three audience members have the expertise necessary to follow along past the first few slides. Please be assured that the audience already knows you’re smart, competent, and can publish complex ideas in top-tier, peer reviewed journals. They want to know if you’re also able to share your ideas with non-experts (i.e. students). The research talk will generally be scheduled for one hour, which will include a short introduction and a ten minute question and answer session at the end. I made sure to avoid 1) going over the allotted time because it can imply time management issues or 2) finishing the presentation in under 30 minutes, which might  suggest a lack of content/results. I did my best to aim for a 40-50 minute presentation. Most audience members will not mind if they get to leave a little early. Also, presenters usually have about 15 minutes to prepare before the talk. But be forewarned that when earlier meetings run long, you’ll have to jump into the presentation without any prep time. Proposal Talk The job interview proposal talk is a lot like a graduate student proposal talk (also sometimes known as a qualifying exam) but with a slightly different focus. The primary focus of a qualifying exam is to defend your ideas.  In addition to defending your ideas during the job proposal talk, you’re expected to provide tangible ways of pursuing the ideas and mentoring young researchers along the way. Similar to the written proposal, the general outline for most proposal talks is 1) introduce a problem that needs to be solved, 2) mention how others are trying to solve it, 3) introduce how you are trying to solve it, and 4) discuss why your method is better and 5) mention the possible implications of your work. I started my proposal talk with an outline slide. While everyone was getting situated they were able to view the slide and familiarize themselves with my flavor of research. Below is an outline slide example: Not all audience members will have read your proposals or attended the previous research talk, so you’ll also w

Structural Biology: Sulfonamide drugs may harm nervous systems by inhibiting an enzyme

Interesting way to depict micelles.

CAUTION! BAD TOC GRAPHIC DO NOT READ!

Environment: Under current U.S. environmental and health regulations, federal agencies could miss identifying risks associated with new nanomaterials