Resolution of Enantiomers - Chemical Engineering Video Lecture

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.