Favorite Reaction – SN2

My all-time favorite chemical reaction has to be the SN2. This may sound like a cop-out answer to Rachel Pepling’s question, since the SN2 is arguably the second* simplest organic reaction ever, almost more a mechanistic step than a reaction per se.

sn2 nucleophilic substitution bimolecularHowever, its simplicity is deceiving. Our old familiar SN2 reaction is an absolute treasure trove of organic chemistry principles. The details of this reaction exquisitely illustrate nucleophilicity/electrophilicity, stereochemistry, sterics, kinetics, solvent effects, and so very much more. There are ritzy versions of the SN2 (e.g., Mitsunobu) for those of us that want a little extra sophistication. The SN2 can even cure – or cause – cancer (DNA alkylation).

An Overview of SN2
For anyone stumbling across this that hasn’t brushed up on organic chemistry in a while, an SN2 reaction is a bimolecular nucleophilic substitution reaction. (The “S” and the “N” come from two of those words – I’ll let you guess which ones – and the “2” represents bimolecular). In general, a substitution reaction is one in which a little piece of a molecule falls off and gets replaced by another new piece. The piece that falls off is called a “leaving group” (shown in red below), and the new piece that will get added on is given the less self-explanatory name “nucleophile” (shown in blue below). This reaction is bimolecular because it involves two molecules coming together at the same time – Molecule A and Molecule B.

bimolecular nucleophilic substitution reaction

I would argue that an entire organic chemistry course could be taught based on the SN2 reaction**, but here I’ll try to just touch on some of the important principles. Hopefully I can make my case that the SN2 is basically awesome.***

Fundamental Principle #1 – Nucleophilicity/Electrophilicity
nucleophilic substitution bimolecularA nucleophile – the blue thing in the scheme above – is something that “loves nuclei” or “loves things that have a positive charge” (the nucleus of an atom is positively charged because that’s where the protons hang out). Unsurprisingly, really good nucleophiles are often themselves negatively charged, because nothing loves a positive like a negative. Conversely, the object of the nucleophile’s attraction (in this case a carbon attached to a leaving group) is called an electrophile – it loves electrons (or things with negative or partial negative charges). This carbon has a partially positive charge… but I won’t get into that here.

Fundamental Principle #2 – Stereochemistry
In an SN2, the nucleophile attacks a tetrahedral (sp3 hybridized) carbon atom that is bound to a leaving group (red). Simultaneously, that leaving group takes off. Because the leaving group is still in the process of leaving while the nucleophile is coming in, they can’t both be in the same place at the same time. In fact, the nucleophile attacks the tetrahedral carbon from the exact opposite side of where the leaving group is located. As a result, the stereochemistry of the tetrahedral carbon in the product is inverted from the original. (What the heck is stereochemistry? See here.)

nucleophilic substitution bimolecular

Fundamental Principle #3 – Sterics
Some carbons that are attached to splendid leaving groups might never be attacked by a nucleophile for an SN2 reaction. The likely cause of this lack of reactivity is sterics, or the presence of nearby molecular clutter that gets in the way of a nucleophile weasling its way in to attack the carbon. At the extremes, a carbon that has three other carbon atoms attached to it is too hindered for SN2 (below right). In an opposite scenario, a carbon with three hydrogens attached (below left) is a prime target for a nucleophile, since those tiny hydrogens don’t get in the way at all.

nucleophilic substitution bimolecular

Fundamental Principle #4 – Kinetics
Because two different molecules must come together at the same time for an SN2 to occur, the rate of the reaction depends on the presence of both molecules. The reaction should go quite fast if there is a lot of both molecules A and B around, because they’re pretty likely to run into each other. If there is a lot of one molecule but not the other, the reaction will be slower. And the reaction will be slowest if there isn’t much of either molecule around. If the rate of a substitution reaction only seems to be affected by the starting concentration of one molecule but not the other, then you know you’re dealing with something other than an SN2.

A Fancy Version – Mitsunobu

mitsunobu SN2

Yup, fancy.

The First Chemotherapy Ever – SN2 in Action
nucleophilic substitution bimolecular dna alkylationThe prototype chemical treatment for cancer was a nitrogen mustard (HN2). Like most chemotherapy agents, it works by killing cells. That sounds like a bad thing, but it turns out to be a good thing if the victims are cancerous cells. HN2’s cytotoxicity is due to its ability to alkylate DNA (attach a carbon atom/carbon chain onto a place where it doesn’t belong on a DNA strand). It alkylates DNA by a sequence of SN2 reactions, resulting in cross-linkages between portions of DNA.

HN2 nitrogen mustard SN2 dna alkylation

That’s SN2 in a nutshell. Thanks Rachel for the writing prompt!

*the simplest would have to be proton transfer
**yes it can even segue into reactions of aromatics
***it’s also my initials …except the “2″ of course
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FDA Warning to Brazilian Blowout. Also, Fume Hood for Hair?

I interrupt this blog from its regularly-scheduled hiatus* to comment on a new tidbit of information about Brazilian Blowout that has recently come to light. The FDA has issued an official warning letter to Mike Brady, the CEO of GIB, LLC (aka Brazilian Blowout), citing two major violations of their original BB product. Namely, the FDA declares Brazilian Blowout to be (1) an adulterated cosmetic and (2) a misbranded cosmetic.

brazilian blowout fda warning methylene glycolThe warning letter is fairly straightforward. The original BB hair straightening formula is described as “adulterated” because it contains an ingredient that is potentially harmful when the product is used as prescribed. This ingredient, of course, is formaldehyde (aka methylene glycol). Secondly, the product is misbranded because it claims to be formaldehyde-free when… it isn’t.

Clearly BB needs to cease the “formaldehyde-free” branding, but should they pull the product from the market? A lot of people really like the results of the original formula, and are willing to pay large sums of money to get their hair straightened this way. Notably, the newer Brazilian Blowout Zero product, which truly doesn’t contain formaldehyde, doesn’t seem to work like the original, at least according to numerous comments on this earlier post.

The way I see it, there are two questions that need to be answered:

(1) Is there a ventilation technique that will enable use of this product without hazard to the stylist or the customer during the application? (2) After the customer leaves the salon, do formaldehyde fumes continue to be expelled from the hair over the course of hours, days, or weeks? If so, are the fumes in levels high enough that there should be a health concern? If the answers to these questions are (1) yes and (2) no, then Brazilian Blowout’s problems with the FDA should be reconcilable in a way that all parties can be happy.

Here is my suggestion for how to ensure safety for the stylist, customer, and other nearby persons during application of Brazilian Blowout. I think it’s pretty self-explanatory, especially if you’ve ever used a glovebox. Make it pink or something, so maybe it won’t scare the customers away:

brazilian blowout safe application methylene glycol formaldehyde

*I have now begun the last year of my PhD program, so spare time has become very scarce (i.e., nonexistent) over the last few months. As a result, unfortunately, this blog has gotten pushed to the wayside. I miss it dearly, and hope to be able to get back to it when things settle down. I’ve never gotten a PhD before, so I’m a little unclear on when exactly things “settle down”, but they’ve got to sometime (right?).
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A Deuterated Mouse: Isotopes and Phys. Org.

heavy mouse deuterium isotopeWhat would happen, hypothetically, if a baby mouse could grow up eating only deuterated food and water? Could you make an unusually heavy mouse? Continue reading

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What I Want to Be When I Grow Up

I began this blog last September as an experiment. Like any good experiment, this particular one was designed to answer a question. Over the past few weeks, I’ve been mulling over the “data” I’ve acquired through this experiment, and realized I have sufficient data to draw a conclusion. Since this blog is about science (and because I’m kind of a nerd), it seems appropriate to share my results in the format of a scientific paper. What follows comes complete with an abstract, so feel free to just read that or skip to the conclusions (like one normally does with scientific papers) if you just want to get the gist of it. There’s also supporting information at the end, with gratuitous pie charts. Here goes: Continue reading

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Sour Patch Kids are Full of Protons

Sour Candy ChemistryTake a look at the ingredient list on the back of a Sour Patch Kids bag the next time you go to the movie theater, and you probably won’t be surprised to discover that this gummy candy contains a lot of chemicals. With such a complex ingredient list, you might be surprised to learn that the key feature of these snacks – their sourness – is actually quite simple. The sourness comes not from one chemical, not even one element, but from just one tiny little fraction of an atom. Continue reading

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You know you spend too much time in the lab when…

friedrich august kekule von stradonitz benzeneI hope I’m not the only chemist who frequently wakes up in the morning to realize I’d just been wasting my sleep time by dreaming about chemistry. Kekule famously dreamt a useful dreamprobably a daydream, but it was about the structure of benzene being analogous to a snake chasing its tail, but mine – so far – have been just silliness. Here are a couple from the past week: Continue reading

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Low Hanging Fruit

This past week, I met with a visiting professor who commented that chemistry research is harder and more complex than it used to be. Most of the “low-hanging fruit” has already been picked, and the major problems facing chemistry today require relatively massive amounts of time and resources to solve. Continue reading

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Chemistry of Morphine, Heroin, and Lemon Poppy Seed Cake

poppy seeds heroin morphine drug testYou’ve heard the warnings – don’t eat poppy seeds before taking a drug test. The seeds can trigger a false positive reading for opioids, making your potential employer think you could be a heroin addict. A few years back, Mythbusters reproduced the anecdotes, showing that just two poppy seed bagels was enough to make Jamie test positive for drugs. (Other studies have shown the same thing.) Continue reading

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A Lexicon of Chemistry Terms to Review Before Attending Your Kid’s Thesis Defense

Hypothetically, let’s say that (1) I graduate someday and (2) my parents come out for my thesis defense. Since I am, in fact, not curing cancer, I fear that my defense will be a snoozer for any non-chemists such as said parents. Thus, I’ve decided to begin preparing them for the occasion. (I have not yet informed them of this.) In addition to abundant coffee and perhaps a “Where’s Waldo” hidden in my PowerPoint slides, it seems beneficial to provide them with a glossary of terms they might hear.where's waldo thesis defense

Continue reading

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This Just In: Grow a Bigger Brain Without Getting Off the Couch!

A couple of months ago, PNASProceedings of the National Academy of Sciences published an article demonstrating that aerobic exercise can increase the size of your hippocampus. Well, for those of you interested in growing your gray matter without breaking a sweat, this latest (unrelated) study is for you! Continue reading

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A Proposed Modification to the English Language

A Question
I begin this post with a serious question, particularly for non-chemists. If I say the following to you, does it make sense?

I would love to be done with my taxes by now, but there’s such a high activation barrier to getting starting that I keep putting them off.

Is “activation barrier” something people say?! I mean, is that a thing? Continue reading

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Sunny Days (and the chemistry they cause)

Winter is finally commencing its retreat in my part of the country, which means we’re actually getting a little sunshine! Clear blue skies usually inspire thoughts of barbecues or pool parties, but they could just as relevantly inspire thoughts about chemistry. (Especially because it’s still too cold for much outdoor funand since I am a graduate student who has no time for barbecues and pool parties.) Continue reading

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Seriously Dude… Where’s My Car?

Fidelity of neural reactivation reveals competition between memoriesSometimes it seems like all the junk accumulated in our memories makes it harder to remember new things. For example, if you drive in to work every morning and have to hunt for parking, it may be difficult at the end of each day to remember where exactly you left your car. Your memory of parking that morning is clouded by all the competing memories of mornings past. Continue reading

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Animals and Aminals (and two kinds of metathesis)

unless you've been living under a rock earthwormUnless Even if you’ve been living under a rock, you know what an animal is. But do you know what an aminal is? Well, it’s two things:

(1) A metathesis of the word “animal”
(2) A chemistry term for a particular arrangement of atoms (functional group).

And do you know what a metathesis is? Well, it’s two things: Continue reading

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Those Devilish CO2 Bubbles

co2 bubbles in beerIf you’ve ever stared pensively into a mug of beerunless it was Guinness, then you might be picturing N2 bubbles, then you probably have a good mental picture of what CO2 bubbles look like. Tiny little things that wiggle their way up or cling to the sides of the glass… nothing terribly exciting, right? Continue reading

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Reliable Information is Written Respectfully

This is part 3 of a 3ish part series on navigating the language of chemicals. Read an introduction, part 1, part 2, and part 2.5 if you wish.

When researching the chemicals in a product, the curious consumer will most likely encounter information presented in several different styles and with varying degrees of usefulness. The goal of this post is to look at how a reader can begin to evaluate the reliability of an information source. Continue reading

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In Defense of Aldehydes

Consider this an unscheduled footnote to part 2 of the ongoing 3 part series on navigating the language of chemicals. Read an introduction, Part 1, and Part 2 if you wish; Part 3 should appear on Monday.

dr jekyll and mr hyde aldehydesWhile reading about the presence of formaldehyde in hair products, I’ve stumbled across descriptions of a few products that proudly claim to be not only formaldehyde free, but free of any “hyde” or any chemical in the “hyde” family. Though this phrase is relatively harmless, I do find the wording a teensy bit unfair to some of the friendly aldehydes out there. So just to set the record straight, here is why you shouldn’t hate hydes just because they’re hydes. Continue reading

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Myths, Hyperboles, and Buzzwords about Chemicals

This is part 2 of a 3 ± 1 part series on navigating the language of chemicals. Read an introduction and part 1 if you wish.

Efforts to make sense of the health and safety information for any given product can be complicated by pervasive buzzwords, hyperboles, and myths relating to chemicals. In order for the reader/viewer to stay calm and think scientifically, it’s important to be aware of the presence of these attitude-modifiers. Continue reading

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What Is – And What Isn’t – A Chemical

This is Part 1 of a 3 ± 2 part series on navigating the language of chemicals. Please see this earlier post for an introduction.

suave shampoo what is a chemicalIf you try to look up the ingredients in Suave shampoo – Google search Suave shampoo ingredients – the number one hit is a site that condemns the Suave shampoo brand, and instead directs you to read a review of their favorite “herbal shampoo.” In said review, the writer makes the following statement: Continue reading

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The Chemistry of Our Pets

guinea pigs scurvy vitamin c ascorbic acid tortoises uric acid chinchillas cedar plicatic acidMy proposed mini series on navigating the language of chemicals shall begin on Monday. For now, please enjoy some cute furry and/or reptilian animals (and their chemistry!) on the C&EN Newscripts blog HERE. They very kindly offered to let me write a guest post, and I’m quite grateful for the opportunity to contribute something. The Newscripts blog, by the way, regularly puts up fun chemistry tidbits, so you should check it out if you’re not yet familiar!

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