WEBVTT

00:00:00.000 --> 00:00:01.750


00:00:01.750 --> 00:00:05.020
Today, we'll be talking about
how to separate enantiomers

00:00:05.020 --> 00:00:05.780
from each other.

00:00:05.780 --> 00:00:08.920
Enantiomers are like your
left and right hands.

00:00:08.920 --> 00:00:10.610
They are mirror
images of each other,

00:00:10.610 --> 00:00:12.880
but they look almost identical.

00:00:12.880 --> 00:00:16.630
Remember that much like we
use right and left to describe

00:00:16.630 --> 00:00:20.760
which hand is which, scientists
use the letters S and R

00:00:20.760 --> 00:00:23.360
to designate which
enantiomer is which,

00:00:23.360 --> 00:00:26.270
when you only have
one chiral center.

00:00:26.270 --> 00:00:29.260
However, when you have
multiple chiral centers,

00:00:29.260 --> 00:00:32.310
there are other ways of
designating enantiomers.

00:00:32.310 --> 00:00:34.130
But we won't be getting
into that today,

00:00:34.130 --> 00:00:36.920
because that's much
more complicated.

00:00:36.920 --> 00:00:39.900
Here we have a set
of enantiomers.

00:00:39.900 --> 00:00:43.380
This is the S confirmation
of thalidomide,

00:00:43.380 --> 00:00:46.320
and here on the right
is the R confirmation.

00:00:46.320 --> 00:00:50.120
Why does it matter that we have
two different confirmations?

00:00:50.120 --> 00:00:53.170
Well, you can see the
difference quite clearly

00:00:53.170 --> 00:00:55.930
at the chiral center,
where one of the groups

00:00:55.930 --> 00:01:00.100
points into the screen and the
other points out of the screen.

00:01:00.100 --> 00:01:04.319
And just because of the
simple change in confirmation,

00:01:04.319 --> 00:01:08.120
that S version was found to
lead to terrible birth defects

00:01:08.120 --> 00:01:09.730
when consumed by mothers.

00:01:09.730 --> 00:01:12.660
And because of
this, drug companies

00:01:12.660 --> 00:01:16.750
now try to make sure that the
active ingredient in their drug

00:01:16.750 --> 00:01:19.900
is only one
particular enantiomer.

00:01:19.900 --> 00:01:22.740
So how would we go about
separating these two?

00:01:22.740 --> 00:01:25.430
One technique that you
could use is chiral column

00:01:25.430 --> 00:01:26.770
chromatography.

00:01:26.770 --> 00:01:30.190
You would need a stationary
phase that is chiral,

00:01:30.190 --> 00:01:32.990
meaning something that
will only bind either

00:01:32.990 --> 00:01:37.660
to the R confirmation or the
S confirmation of your desired

00:01:37.660 --> 00:01:38.970
enantiomer.

00:01:38.970 --> 00:01:41.980
So how does the chiral
stationary phase only

00:01:41.980 --> 00:01:44.820
bind to one of the enantiomers?

00:01:44.820 --> 00:01:48.450
Picture the two enantiomers
as your right and left hand.

00:01:48.450 --> 00:01:51.090
If your right hand tries
to shake another person's

00:01:51.090 --> 00:01:55.230
right hand it seems normal,
the two fit together properly.

00:01:55.230 --> 00:01:58.910
But if your right hand tries
to shake your own left hand,

00:01:58.910 --> 00:02:01.660
it doesn't seem like
they line up quite right.

00:02:01.660 --> 00:02:03.900
That's the exact same
thing that happens

00:02:03.900 --> 00:02:08.280
with the chiral stationary
phase and the wrong enantiomer.

00:02:08.280 --> 00:02:11.410
Next, what you do is you'd load
that mixture of enantiomers.

00:02:11.410 --> 00:02:15.430
So on top here, you
might see that you

00:02:15.430 --> 00:02:19.240
have some kind of
band of your mixture.

00:02:19.240 --> 00:02:21.460
This is racemic,
meaning that it has

00:02:21.460 --> 00:02:24.180
a 50/50 mixture of enantiomers.

00:02:24.180 --> 00:02:26.730
So that's what you're
seeing here in the yellow.

00:02:26.730 --> 00:02:28.580
If we take a closer
look, you'll see

00:02:28.580 --> 00:02:34.600
that this has some
of the S confirmation

00:02:34.600 --> 00:02:36.995
and some of the R
confirmation too thrown in.

00:02:36.995 --> 00:02:40.300


00:02:40.300 --> 00:02:44.080
And as this moves through
the stationary phase,

00:02:44.080 --> 00:02:48.220
so once you open up the
stop cock, what you'll see

00:02:48.220 --> 00:02:52.570
is that if the R
enantiomer was the one that

00:02:52.570 --> 00:02:55.390
binds tightly to the
stationary phase,

00:02:55.390 --> 00:02:57.950
it won't move very quickly.

00:02:57.950 --> 00:03:02.050
But with the S enantiomer,
it might be racing through

00:03:02.050 --> 00:03:03.780
since it's not
really interacting

00:03:03.780 --> 00:03:06.130
that much with the
stationary phase,

00:03:06.130 --> 00:03:09.310
and prefers to interact
with the mobile phase.

00:03:09.310 --> 00:03:14.110
Once you've collected all of
the S enantiomers in your flask,

00:03:14.110 --> 00:03:16.250
all you'll have
left in the column

00:03:16.250 --> 00:03:19.430
is the R enantiomer, which
is pretty tightly bound

00:03:19.430 --> 00:03:21.690
to the chiral stationary phase.

00:03:21.690 --> 00:03:24.410
Next, what you'd do is
when you have this column,

00:03:24.410 --> 00:03:26.660
you'd want to pour
in lots of solvent

00:03:26.660 --> 00:03:29.540
so that you can get the
R enantiomer to come out.

00:03:29.540 --> 00:03:32.570
Because as this pushes
down through the column,

00:03:32.570 --> 00:03:35.480
it will take the R
enantiomer with it,

00:03:35.480 --> 00:03:40.300
giving you just the R
enantiomer in your flask.

00:03:40.300 --> 00:03:44.270
And there you've done a
successful chiral resolution.

00:03:44.270 --> 00:03:48.650
The same principle can also be
applied to gas chromatography.

00:03:48.650 --> 00:03:52.220
Let's quickly review how
gas chromatography works.

00:03:52.220 --> 00:03:57.710
You insert your sample in
here, a gas flows through,

00:03:57.710 --> 00:04:01.070
and then it goes into
this long to that

00:04:01.070 --> 00:04:03.910
contains the stationary
phase and mobile phase,

00:04:03.910 --> 00:04:06.240
and goes to the detector.

00:04:06.240 --> 00:04:09.430
And if we were to
zoom in on this--

00:04:09.430 --> 00:04:12.510
and draw this just
kind of a long tube--

00:04:12.510 --> 00:04:17.740
again what you'd see is that if
this time the stationary phase

00:04:17.740 --> 00:04:21.970
was attracted to the
S enantiomer instead,

00:04:21.970 --> 00:04:25.700
you'd see that the S enantiomer
is sticking to the sides,

00:04:25.700 --> 00:04:27.690
sticking to the
stationary phase,

00:04:27.690 --> 00:04:32.600
while the R enantiomer races
through with the mobile phase.

00:04:32.600 --> 00:04:34.830
So there are actually
a number of other ways

00:04:34.830 --> 00:04:37.400
you can separate
enantiomers, but those

00:04:37.400 --> 00:04:39.700
tend to be much
more complicated.

00:04:39.700 --> 00:04:42.590
These are just two of the
common ways you can do it.

00:04:42.590 --> 00:04:44.460
And in both of
them, whether you're

00:04:44.460 --> 00:04:49.050
doing column chromatography with
a solid stationary phase or gas

00:04:49.050 --> 00:04:52.290
chromatography was a
liquid stationary phase,

00:04:52.290 --> 00:04:56.490
the important thing to remember
is that your stationary phase

00:04:56.490 --> 00:05:01.020
should be chiral and bind to
the enantiomer that you want.

00:05:01.020 --> 00:05:01.556