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Resolution of enantiomers

Understand how enantiomers can be isolated from a racemic mixture using chromatography with a chiral stationary phase. By Angela Guerrero. . Created by Angela Guerrero.

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  • male robot donald style avatar for user Trevør Hylånd
    Should the absolute configuration of the stationary phase match the absolute configuration of the particular enantiomer you want to have elute last? So if you want the R-enantiomer to elute last, you'd use an R-enantiomer stationary phase so that the S-enantiomer would elute first?
    (17 votes)
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    • duskpin ultimate style avatar for user Becca
      It most likely depends on other factors besides the enantiomer configurations alone. Regardless, you would have to identify the absolute configuration with plane polarized light experiments. So why would you have a preference for which enantiomer elutes first anyhow?
      (3 votes)
  • leaf green style avatar for user Quynh Tram
    At , why would the stationary phase in general should be chiral? In chromatography generally, mustn't the stationary phase only be polar?
    (1 vote)
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    • blobby green style avatar for user sonictif2
      As explained in , I think the idea is that the chirality of the stationary phase will help ensure that only one of the enantiomers would be particularly attracted to it, like the idea of "shaking hands" your right hand should shake someone else's right hand - it would be harder for you to shake someone's left hand.

      If the stationary phase was only polar, both enantiomers would be equally attracted to it (since the polarity would probably be the same between the two enantiomers), and thus no separation would be achieved, and the whole point of the exercise is to SEPARATE the two. So, we also need the stationary phase to be chiral and thus, attractive to only one of the enantiomers.
      (11 votes)
  • piceratops ultimate style avatar for user Darmon
    The speaker repeatedly refers to the two enantiomers as different CONFORMATIONS; this is incorrect! Chirality centers differ in the fixed spatial arrangement of atoms around those centers, leading to two different CONFIGURATIONS. The term CONFORMATION is used to describe a particular spatial arrangement of atoms that arises due to rotation about single bonds, and is therefore subject to interconversion with other such states. The distinction between these two terms is extremely important and highly emphasized by many organic chemistry instructors and professors; this mistake should be corrected. The first instance of this error occurs at in the video.
    (7 votes)
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  • piceratops tree style avatar for user seanthebomb
    How would separating enantiomers via gas chromatography work? Don't enantiomers have the same physical properties? (i.e. same boiling points)
    (4 votes)
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    • duskpin ultimate style avatar for user Becca
      Yes, they do have the same physical properties. And with interactions with achiral molecules, this would be the case. However, if a racemic compound interacts with a chirally pure molecule, they can have completely different reactions.

      An example of this would be the drug thalidomide. Thalidomide was a drug used in the 60's to combat morning sickness in pregnant women. However, it also caused severe birth defects. This is because one of the enantiomers did indeed help reduce morning sickness. However, the other one interacted differently and induced birth defects. This can happen because amino acids and other building blocks of life are chiral.

      Similarly, different interactions occur between the different enantiomers and the chirally pure stationary face. Usually, one enantiomer has a high affinity to bind the stationary phase, so one enantiomer will separate out sooner than the other.

      Enantiomer interactions only are the same when the other compounds interacting with it are achiral. When interacting with a chirally pure compound, there can be notable differences.
      (5 votes)
  • blobby green style avatar for user Dania Drewing
    I can't stop imagining April Kepner when she talks. :-)
    (2 votes)
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  • blobby green style avatar for user esnartmupeta500
    What are some industrial applications of chromatography?
    (1 vote)
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  • blobby green style avatar for user Kara Reinheimer
    How can you tell when one enantiomer has completely come through the apparatus?
    (1 vote)
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Video transcript

Today, we'll be talking about how to separate enantiomers from each other. Enantiomers are like your left and right hands. They are mirror images of each other, but they look almost identical. Remember that much like we use right and left to describe which hand is which, scientists use the letters S and R to designate which enantiomer is which, when you only have one chiral center. However, when you have multiple chiral centers, there are other ways of designating enantiomers. But we won't be getting into that today, because that's much more complicated. Here we have a set of enantiomers. This is the S confirmation of thalidomide, and here on the right is the R confirmation. Why does it matter that we have two different confirmations? Well, you can see the difference quite clearly at the chiral center, where one of the groups points into the screen and the other points out of the screen. And just because of the simple change in confirmation, that S version was found to lead to terrible birth defects when consumed by mothers. And because of this, drug companies now try to make sure that the active ingredient in their drug is only one particular enantiomer. So how would we go about separating these two? One technique that you could use is chiral column chromatography. You would need a stationary phase that is chiral, meaning something that will only bind either to the R confirmation or the S confirmation of your desired enantiomer. So how does the chiral stationary phase only bind to one of the enantiomers? Picture the two enantiomers as your right and left hand. If your right hand tries to shake another person's right hand it seems normal, the two fit together properly. But if your right hand tries to shake your own left hand, it doesn't seem like they line up quite right. That's the exact same thing that happens with the chiral stationary phase and the wrong enantiomer. Next, what you do is you'd load that mixture of enantiomers. So on top here, you might see that you have some kind of band of your mixture. This is racemic, meaning that it has a 50/50 mixture of enantiomers. So that's what you're seeing here in the yellow. If we take a closer look, you'll see that this has some of the S confirmation and some of the R confirmation too thrown in. And as this moves through the stationary phase, so once you open up the stop cock, what you'll see is that if the R enantiomer was the one that binds tightly to the stationary phase, it won't move very quickly. But with the S enantiomer, it might be racing through since it's not really interacting that much with the stationary phase, and prefers to interact with the mobile phase. Once you've collected all of the S enantiomers in your flask, all you'll have left in the column is the R enantiomer, which is pretty tightly bound to the chiral stationary phase. Next, what you'd do is when you have this column, you'd want to pour in lots of solvent so that you can get the R enantiomer to come out. Because as this pushes down through the column, it will take the R enantiomer with it, giving you just the R enantiomer in your flask. And there you've done a successful chiral resolution. The same principle can also be applied to gas chromatography. Let's quickly review how gas chromatography works. You insert your sample in here, a gas flows through, and then it goes into this long to that contains the stationary phase and mobile phase, and goes to the detector. And if we were to zoom in on this-- and draw this just kind of a long tube-- again what you'd see is that if this time the stationary phase was attracted to the S enantiomer instead, you'd see that the S enantiomer is sticking to the sides, sticking to the stationary phase, while the R enantiomer races through with the mobile phase. So there are actually a number of other ways you can separate enantiomers, but those tend to be much more complicated. These are just two of the common ways you can do it. And in both of them, whether you're doing column chromatography with a solid stationary phase or gas chromatography was a liquid stationary phase, the important thing to remember is that your stationary phase should be chiral and bind to the enantiomer that you want.