Who cares about Isomerism?

If you want to learn more about drug design you’ll need to know about it!

Co-authored by Susan from my Innovations in Chemistry class.

This is part of my ongoing experimentation on how to deliver chemistry topics to students in a more engaging and contextually relevant way.

One of my students was interested in learning more about Methamphetamine after seeing the show “ Breaking Bad’, so I grabbed a molecular modeling kit and built out the structure, and left it on a bench in the IDEA LAB.

What is the IDEA LAB?

It’s a room where students create at Marymount School of New York. It’s a sandbox for students to imagine and build, engineer and design, prototype, and make.

The Methamphetamine molecular model sat on the bench for a few days when another student walked in and asked what is that?

I answered Methamphetamine.

She replied: it’s like Adderall, right?

Yes: I replied.

Can we learn more about it she asked.

Yes: I said.

So in class the next day the students looked up the formula and structure of Amphetamine.

Adderall and Mydayis[8] are trade names[note 2] for a combination drug called mixed amphetamine salts containing four salts of amphetamine.

We noticed when the molecule was built out there were two versions. Why is this? What is this phenomenon called? It turns out there are two isomers of Amphetamine. This is a phenomenon called stereoisomerism, the mixing of isomeric chemicals (all the same chemicals) to create different reactions, almost like locks.

For instance, we built out the molecular forms of different Methamphetamines, signifying the differences with a different colored molecule amid the black and white hydrogens and oxygens. We built out the methamphetamine in two different forms, inverting the different colored molecules to provide a different medical effect on the body once ingested.

Adderall is a combination of four amphetamine salts (D-amphetamine saccharate, D- amphetamine sulfate, D,L-amphetamine sulfate, and D,L-amphetamine aspartate), with a 3 : 1 ratio of D-isomer to L-isomer. Adderall is the brand name for Amphetamine was discovered in 1887 and exists as two enantiomers, D and L structures.

Enantiomers are stereoisomers that are non-superimposable mirror images. Enantiomers differ at the configuration of every stereocenter. They can be understood in terms of handedness, like gloves for the right or left hands.

Isomerism is the concept of “flipping the molecule,” or building out a structure nearly identical to another with one minor compositional flaw that completely changes the drug’s effects on the body. A common example are the two types of Lactic Acid. However, everywhere in the pharmaceutical industry there is isomerism depending on where the atoms in each drug tend to move to.

So the student’s interest in Adderall led us to learning more about Isomerism. Right throughout this module there was no problem with student engagement. What I am finding is that if you allow students to choose the content and let them co-design the learning experience with you, everyone wins.

Isomerism is important because it allows for the existence of molecules with the same chemical formula but different properties. This can have a significant impact on the way that these molecules interact with each other and with the environment.

For example, in the field of pharmaceuticals, isomerism can be used to create drugs that are more effective and less toxic than their racemic counterparts. Racemic mixtures are composed of equal amounts of two enantiomers, which are mirror images of each other. In some cases, one enantiomer may be more effective than the other, or it may have fewer side effects. For example, the drug thalidomide was originally marketed as a safe sedative for pregnant women. However, it turned out that one of the isomers of thalidomide was a powerful teratogen, causing birth defects in thousands of children.