What the chlorite-iodide reaction taught me.

Posted on September 26, 2011September 26, 2011 by jstemwedel

Since 2011 is the International Year of Chemistry, the good folks at CENtral Science are organizing a blog carnival on the theme, “Your favorite chemical reaction”.

My favorite chemical reaction is the chlorite-iodide reaction, and it’s my favorite because of the life lessons it has taught me.

The reaction has overall stoichiometry:
ClO₂^– + 4 I^– + 4 H⁺ = 2 I₂ + Cl^– + H₂O
Written out that way, as a simple set of reactants and products, it doesn’t look that exciting, but when the reaction is run in a continuous flow stirred tank reactor (CSTR), where reactions are flowed in and products are removed, it can exhibit oscillatory behavior. The oscillations in the concentrations of iodine (I₂) and iodide (I^–) can be tracked experimentally, the former by measuring UV absorbance at 460 nm, the latter by measuring the potential of an ion-specific electrode.

An early study of the kinetics of this reaction determined that it “is catalyzed by the iodine product, and the autocatalysis is inhibited by iodide ion.” (Kern and Kim 1965, 5309) In 1985, Epstein and Kustin proposed the first mechanism for this reaction to account for the oscillatory behavior, one that includes 13 elementary steps and 12 chemical species. Two years later, Citri and Epstein proposed an improved model mechanism with 8 elementary mechanistic steps and 10 chemical species. The Citri-Epstein model proposes a different set of elementary steps to describe the oxidation of iodide by chlorite. In addition, it eliminates the intermediate IClO₂^–, “whose existence has been called into question elsewhere.” (Citri and Epstein 1987, 6035) The resulting model mechanism seemed to produce better agreement between predicted and measured concentrations of iodide and iodine than that given by the earlier model.

The chlorite-iodide reaction also happens to have been the reaction at the center of most of my research for my Ph.D. in chemistry.

Here are some of the lessons I learned working with the chlorite-iodide reaction:

Experimental tractability matters, at least when you’re doing experiments. The general thrust of my research was to work out clever ways to perform empirical tests of proposed mechanisms for oscillating chemical reactions, but the chlorite-iodide reaction was not the first reaction I worked with. I started out trying to make some clever measurements on another reaction, the minimal bromate oscillator (MBO). However, after maybe six months of fighting to set up the conditions where the MBO would give me oscillations, I had to make my peace with the idea that its “small” region in phase-space with oscillatory behavior was really, really small. Luckily, in my reading of the relevant literature on the experimental and theoretical approaches we were taking, I had come across a similar inorganic chemical oscillator with an “ample” oscillatory region, one which promised to make my time in the lab exponentially less frustrating. That’s right, the chlorite-iodide reaction was my rebound system, but we stayed together and made it work.
When your original research project gets stuck, it’s good to have a detailed plan for how to move forward when you talk to the boss. My advisor was really keen for that minimal bromate oscillator that was making my life in the lab a nightmare. So, when I met with him to tell him I wanted to break up with the MBO and take up with the chlorite-iodide reaction, I had to make the case for the new system. I came armed with the articles that described its substantial oscillatory region, and the articles that described the MBO’s tiny one. I prepared some calculations describing how much more precise our pump-rates would need to be to find MBO oscillations, and catalogues that listed the prices of the new equipment we would need. I brought the articles proposing mechanisms for the chlorite-iodide reaction so I could display the virtues of their elementary mechanistic steps from the point of view of the kind of experimental probing we had in mind. Because I did my homework and was able to make a persuasive case, the boss was happy to let me start working with the chlorite-iodide system right away, and to kiss the minimal bromate oscillator goodbye forever.
Experimental tractability is relative, not absolute (and Materials and Methods often leave stuff out). The chlorite-iodide reaction was certainly easier to work with — within a week, I found oscillations where the literature said I would — but it was not completely smooth sailing. There were pumps that didn’t perform as they should, which meant I was taking them apart and swapping out components. There were days when I couldn’t get any reliable measurements because the pH meter I used with my iodide-specific electrode had been left on for too many hours in a row. And, there were little details I discovered in setting up experimental runs day in and day out that were not fully discussed in the “materials and methods” section of the published papers describing the chlorite-iodide reaction. Reproducibility is hard
Reactions happen in three-dimensional space, not just in reaction space. One of the experimental challenges of the chlorite-iodide reaction is that, to find the dynamical behavior you’re looking for, you have to stir the reactants in the tank reactor at the right speed. Stirring much faster or much slower will change the dynamics of the reaction, as will using a reactor with significantly different internal geometry. (“Dimples” protruding into the cylindrical space inside the reactor are supposed to help you mix the reactants more effectively, rather than giving them the opportunity to hang out unmixed by the walls.) Appropriate stirring speed was not one of the parameters spelled out by the papers whose descriptions of the reaction I was using to get started, nor was reactor geometry. I had to do experiments to work out the stirring speed that (with the geometry of the reaction vessel we had on hand) produced the same behavior as these other papers were reporting. Once I found that stir-speed, I kept that constant for my experimental runs. Also, I made detailed measurements of the reactor we were using, which turned out to be a really good thing when that reactor broke. I was able to take those measurements to the glass-blower’s shop and get replacements (plural) made.
Time well spent in setting things up is frequently rewarded with good data. It was absolutely worth it to spend a couple hours at the beginning of each run calibrating pump flow-rates and checking out the iodide-selective electrode performance with standard solutions, since this let me apply the experimental conditions I wanted to and make accurate measurements. Did I mention that reproducibility is hard?
Qualitative measurements require patience, too. Among other things, I was interested in mapping the edges of regions in phase-space where the chlorite-iodide reaction displayed different kinds of behavior. On one edge, there was a bifurcation where you would find steady state behavior (i.e., stable concentrations of reaction species) that, coming up on the bifurcation point, became tiny-amplitude oscillations that grew. On the other edge, the oscillations had attained their maximum amplitude, but their period (that is, the lag between oscillatory peaks) grew longer and longer until there weren’t any more peaks and the reaction settled into another steady state. The thing was, it was hard to know when you were set up with conditions where the period of oscillation was just really, really long (sometimes around 20 minutes between peaks, if memory serves) or when you had found the steady state. You had to be patient. While I was exploring that edge of the reaction in phase-space, I started thinking maybe that was a good metaphor for certain aspects of graduate school.
You probably can’t measure everything you’d want to measure, but sometimes measuring one more thing can help a lot. As I mentioned above, the Citri-Epstein mechanism for the chlorite-iodide reaction posited ten chemical species in the various steps of the reaction. In a perfect world, you’d want to be able to measure each of those species simultaneously over time as the reaction proceeded. But, as one learns pretty quickly in grad school, this is not a perfect world. When I started with this reaction, published papers were reporting simultaneous dynamical measurements of only two of those species (iodide and iodine). Chloride is one of the hypothesized intermediates, and there are chloride-specific electrodes on the market. However, the membrane in a chloride-specific electrode also reacts with … iodide. Other intermediate species might be measured by various chemical assays if the progress of the reaction could be halted in the samples being assayed. By the end of my graduate research, I had figured out a way to use a flow-through cuvette and a seat-of-the-pants spectral deconvolution technique to measure the time-series of one additional species in the reaction, the chlorite ion (ClO₂^–). This was enough to do some evaluation of the proposed mechanism that was not possible without it.

Later on, when I became a philosopher of science, this work gave me some insights into the circumstances in which chemists are happy to be instrumentalists (e.g., recognizing that the fact that a proposed reaction mechanism was consistent with the observed kinetics of the reaction was no guarantee that this was the actual mechanism by which the reaction proceeded) and the circumstances in which they lean towards being realists (by finding ways to distinguish better proposed mechanisms from worse ones). But back when I was actually getting glassware dirty running the chlorite-iodide reaction, this reaction helped me learn how to be a scientist.

_____

Works cited:
Citri, Ofra, and Irving R. Epstein (1987) “Dynamical Behavior in the Chlorite-Iodide Reaction: A Simplified Mechanism”, Journal of Physical Chemistry 91: 6034-6040.

Epstein, Irving R., and Kenneth Kustin (1985) “A Mechanism for Dynamical Behavior in the Oscillatory Chlorite-Iodide Reaction”, Journal of Physical Chemistry 89: 2275-2282.

Kern, David M., and Chang-Hwan Kim (1965) “Iodine Catalysis in the Chlorite-Iodide Reaction”, Journal of the American Chemical Society 87(23): 5309-5313.

What about Dalibor Sames? The Bengü Sezen fraud and the responsibilities of the PI in the training of new scientists.

Posted on August 29, 2011August 29, 2011 by jstemwedel

Unless you are a chemist or a habitual follower of scientific misconduct stories, it’s possible that you missed the saga of Bengü Sezen.

From 2000 to 2005, Sezen was a graduate student in chemistry at Columbia University, working in the laboratory of then-Assistant Professor Dalibor Sames. She appeared to be a talented scientist in training, and during her graduate studies was lead author on three papers published in the Journal of the American Chemical Society. Columbia University conferred upon her a Ph.D. in chemistry (with distinction).

But, as it turns out, her published results were not reproducible, an issue raised by chemists at Columbia and elsewhere as early as 2002. Further, the results were irreproducible for very good reason: as reported by Chemical & Engineering News, investigations by Columbia University and by the U.S. Department of Health & Human Services (which is home to the Office of Research Integrity) revealed

a massive and sustained effort by Sezen over the course of more than a decade to dope experiments, manipulate and falsify NMR and elemental analysis research data, and create fictitious people and organizations to vouch for the reproducibility of her results.

In the wake of the investigations, Sames has retracted the papers coauthored with Sezen (Sezen refused to retract them on the grounds that she stood by the work), and Columbia has revoked the Ph.D. it granted Sezen.

The evidence from the investigations supports the hypothesis that Bengü Sezen was a liar masquerading as a chemist, that she claimed to have done experiments that she hadn’t, to have obtained NMR spectra that she created (in part) with correction fluid, to have built molecules that she didn’t build. She committed fraud that introduced not just mistakes but lies into the scientific literature.

But she didn’t — she couldn’t — do this alone. She didn’t commit her fraud as a principal investigator (PI). Rather she did it as a scientific trainee, a graduate student working under the supervision of Dalibor Sames (who is currently an Associate Professor at Columbia). It’s worth examining what responsibility Sames bears for what happened here.
Continue reading→

Doing fun chemistry.

Posted on August 2, 2011August 2, 2011 by jstemwedel

You may have noticed by now that the Scientific American Blog Network is having something of a Chemistry Day.

Reading about chemistry is fun, but I reckon it’s even more fun to do some chemistry. So, if you find yourself with a few moments and the need to fill them with chemical fun, here are a few ideas:

Make your own acid-base indicator:

With red cabbage and hot water, you can make a solution that will let you tell acids, bases, and neutral-pH substances apart.

Spend the afternoon classifying the substances in your refrigerator or pantry! Audition alternatives to vinegar and baking soda for your papier mache volcano!

Dye some eggs:

Gather up some plant matter and see what colors you can develop on eggshells.

One interesting thing you might observe is that empty eggshells and eggshells with eggs in them interact differently with the plant pigments. Ponder the chemistry behind this difference … perhaps with the aid of some cabbage-water indicator.

Play around with paper chromatography:

Grab some markers (black and brown markers work especially well), lay down some filter paper (or a paper towel or a piece of a coffee filter), and just add water to observe the pretty effects created when some components of ink preferentially interact with water while others preferentially interact with the paper.

If you like, play around with other solvents (like alcohol, or oil) and see what happens.

Make some mayonnaise:

Even just making canonical mayonnaise is a matter of getting oil and water to play well together, making use of an emulsifier.

But things get interesting when you change up the components, substituting non-traditional sources of oil or of emulsifier. What happens, for example, when an avocado gets in on the action?

Try your hand at spherifying a potable:

Molecular gastronomy isn’t just for TV chefs anymore. If you have a decent kitchen scale and food-grade chemicals (which you can find from a number of online sources), you can turn potables into edibles by way of reactions that create a “shell” of a membrane.

Sometimes you can control the mixture well enough to create little spherical coffee caviar or berry-juice beads. Sometimes you end up with V-8 vermicelli. Either way, it’s chemistry that you can eat.

Building knowledge (and stuff) ethically: the principles of “Green Chemistry”.

Posted on August 2, 2011August 2, 2011 by jstemwedel

Like other scientific disciplines, chemistry is in the business of building knowledge. In addition to knowledge, chemistry sometimes also builds stuff — molecules which didn’t exist until people figured out ways to make them.

Scientists (among others) tend to assume that knowledge is a good thing. There are instances where you might question this assumption — maybe when the knowledge is being used for some evil purpose, or when the knowledge has been built on your dime without giving you much practical benefit, or when the knowledge could give you practical benefit except that it’s priced out of your reach.

Even setting these worries aside, we should recognize that there are real costs involved in building knowledge. These costs mean that it’s not a sure thing that more knowledge is always better. Rather, we may want to evaluate whether building a particular piece of knowledge (or a particular new compound) is worth the cost.

In chemistry, these costs aren’t just a matter of the chemist’s time, or of the costs of the lab facilities and equipment. Some of these costs are directly connected to the chemical reagents being brought together in reactions that transform the starting materials into something new. These chemical reagents (in solid, liquid, or gas phase, pure or in mixtures or in solutions) all come from somewhere. The “somewhere” could be a source in nature, or a reaction conducted in the laboratory, or a reaction process conducted on a large scale in a factory.

Getting a reasonably pure chemical substance in the jar means sorting out the other stuff hanging around with that substance — impurities, leftover reactants from the reaction that makes the desired substance, “side-products” of the reaction that makes the desired substance. (A side-product is a lot like a side-effect, in that it’s produced by the reaction but it’s not the thing you’re actually trying to produce.) When you’re isolating the substance you’re after, that other stuff has to go somewhere. If there’s not a particular way to collect the other stuff and put it to some other use, that other stuff becomes chemical waste.

There’s a sense in which all waste is chemical waste, since everything in our world is made up of chemicals. The thing to watch with waste products from chemical reactions is whether these waste products will engage in further chemical reactions wherever you end up storing them. Or, if you’re not careful about how you store them, they might get into our air or water, or into plants and animals, where they might have undesired or unforeseen effects.

In recent years, chemists have been working harder to recognize that the chemicals they work with come from someplace, that the ones they generate in the course of their experiments need to end up someplace, and to think about more sustainable ways to build chemical compounds and chemical knowledge. A good place to see this thinking is in The Twelve Principles of Green Chemistry (here as set out by Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice, Oxford University Press: New York, 1998, p.30.):

Prevention
It is better to prevent waste than to treat or clean up waste after it has been created.

Atom Economy Synthetic methods should be designed to maximize the incorporation of all materials used in the process into the final product.

Less Hazardous Chemical Syntheses Wherever practicable, synthetic methods should be designed to use and generate substances that possess little or no toxicity to human health and the environment.

Designing Safer Chemicals Chemical products should be designed to effect their desired function while minimizing their toxicity.

Safer Solvents and Auxiliaries The use of auxiliary substances (e.g., solvents, separation agents, etc.) should be made unnecessary wherever possible and innocuous when used.

Design for Energy Efficiency Energy requirements of chemical processes should be recognized for their environmental and economic impacts and should be minimized. If possible, synthetic methods should be conducted at ambient temperature and pressure.

Use of Renewable Feedstocks A raw material or feedstock should be renewable rather than depleting whenever technically and economically practicable.

Reduce Derivatives Unnecessary derivatization (use of blocking groups, protection/ deprotection, temporary modification of physical/chemical processes) should be minimized or avoided if possible, because such steps require additional reagents and can generate waste.

Catalysis Catalytic reagents (as selective as possible) are superior to stoichiometric reagents.

Design for Degradation Chemical products should be designed so that at the end of their function they break down into innocuous degradation products and do not persist in the environment.

Real-time analysis for Pollution Prevention Analytical methodologies need to be further developed to allow for real-time, in-process monitoring and control prior to the formation of hazardous substances.

Inherently Safer Chemistry for Accident Prevention Substances and the form of a substance used in a chemical process should be chosen to minimize the potential for chemical accidents, including releases, explosions, and fires.

At first blush, these might look like principles developed by a group of chemists who just returned from an Earth Day celebration, what with their focus on avoiding hazardous waste and toxicity, favoring renewable resources over non-renewable ones, and striving for energy efficiency. Certainly, thoroughgoing embrace of “Green Chemistry” principles might result in less environmental impact due to extraction of starting materials, storage (or escape) of wastes, and so forth.

But these principles can also do a lot to serve the interests of chemists themselves.

For example, a reaction that can be conducted at ambient temperature and pressure requires less fancy equipment (i.e., equipment to maintain temperature and/or pressure at non-ambient conditions). It’s not just more energy efficient, it’s less of a hassle for the experimenter. Safer solvents are better for the environment and the public at large, but it’s usually the chemists working with the solvents who are at immediate risk when solvents are extremely flammable or corrosive or carcinogenic. And generating less hazardous waste means paying for the disposal of less hazardous waste — which means that there’s also an economic benefit to being more environmentally friendly.

What I find really striking about these principles of “Green Chemistry” is the optimism they convey that chemists are smart enough to figure out new and better ways to produce the compounds they want to produce. The challenge is to rethink the old strategies for making the compound of interest, strategies that might have relied on large amounts of non-renewable starting materials and generated lots of waste products at each intermediate step. Chemistry is a science that focuses on transformations, but part of its beauty is that there are multiple paths that might get us from staring materials to a particular product. “Green Chemistry” challenges its practitioners to use the existing knowledge base to find out what is possible, and to build new knowledge about these possibilities as chemists build new molecules.

And, to the extent that chemistry is in the business of finding new knowledge (rather than relying on established chemical knowledge as a master cook book), these twelve principles seem almost obvious. Given the choice, would you ever want to make a new compound for an application that had the desired function but maximized toxicity? Would you choose a synthetic strategy that generated more waste rather than less (and whose waste was less likely to break down into innocuous compounds rather than more)? Would you opt to perform the separation with a solvent that was more likely to explode if a less explosive solvent would do the trick? Probably not. Of course, you’d be on the lookout for a better way to solve the chemical problem — where “better” takes into account things like cost, experimental tractability, risks to the experimenter, and risks to the broader public (including our shared environment).

This is not to say that adhering to the principles of “Green Chemistry” would be sufficient to be an ethical chemist. Conceivable, one could follow all these principles and still fabricate, falsify, or plagiarize, for example. But in explicitly recognizing some of the costs associated with building chemical knowledge, and pushing chemists to minimize those costs, the principles of “Green Chemistry” do seem to honor chemists’ obligations to the welfare of the people with whom they are sharing a world.