Chemistry of Thalidomide

Hopewell Valley Student Podcasting Network

Chemistry Connections

Pharmaceutical Chemistry

Episode #7

Welcome to Chemistry Connections, my name is Eve O’Leary and I am your host for Episode 7 called Pharmaceutical Chemistry. Today I will be discussing The Thalidomide Tragedy.

Segment 1: Introduction to The Thalidomide Tragedy

Developed in Germany in the 1950s, thalidomide is a sedative drug that was administered to pregnant women experiencing morning sickness and insomnia associated with pregnancy. After its five years spent on the market, it was later discovered that the medicine was the cause for babies being born with a rare birth defect, phocomelia, resulting in severely malformed and underdeveloped limbs.

The majority of these deformities occurred in Canada, the United Kingdom, and West Germany.
Thalidomide was never approved for public consumption in the US
The experiments were extremely poorly designed lacking a placebo group, excluding information for how long the treatment had gone on for, and failed to use a double blind procedure.

The drug was withdrawn from shelves by the German distributor, Chemie Grunenthal on November 26, 1961 and was recalled from British shelves on December 2, 1961.

The British Committee on the Safety of Drugs was established in June 1963, offering detailed regulations for the testing of potentially toxic effects on offspring using rats, mice, and rabbits.
Thalidomide cannot be administered to anyone who is possibly or is pregnant, and is instead used to treat a number of cancers and skin conditions such as leprosy.

Segment 2: The Chemistry Behind The Thalidomide Tragedy

Before we start talking about why thalidomide had the effects that it had, let's start by talking about some of its general properties. Below is the chemical structure of thalidomide compound (C13H10N2O4).

Thalidomide contains several different intermolecular forces:

London Dispersion Forces
Dipole-dipole interactions
Hydrogen bonding
Extremely important in drug design.
More energy is required to break the compounds apart. Has a boiling point of approximately 509.7OC and is insoluble in water

Now that we have a good understanding about the properties of thalidomide, a key understanding of chirality is essential in explaining the issue with the drug. Chirality, key to organic chemistry, is a geometric property used to describe mirror image isomers, called enantiomers, that are not superimposable.

The best analogy for this is your hands. If you were to place the left hand over the right, the spatial arrangement will not be the same.
The nomenclature of chiral molecules is called the R/S system where R stands for “rectus” which means right in Latin and S stands for “sinister.”
Enantiomers share the same physical and reactive properties except for their effect on plane-polarized light.
Thalidomide is a racemic mixture of R and S enantiomers.
The R-enantiomer has sedative properties while the S-enantiomer is teratogenic, meaning that it raises the risk of or causes birth defects.
Specifically, it degrades a cell protein known as SALL4 which is responsible for the full development of limbs and important organs. Unfortunately, the isomers cannot be effectively separated before use as they convert into one another under biological conditions.

See if you can identify the structural difference between the two isomers:

Segment 3: Personal Connections

Thalidomide had a huge impact on the United Kingdom (where my family is from)
My maternal grandmother was actually offered thalidomide when she was pregnant in the 1950s
This past year, I worked as a consulting intern. I was given the opportunity to research and correspond with a number of companies including Bexa, which is a high resolution breast elastography device.
Made me passionate, not only about the biomedical industry, but also women’s healthcare in general.
If I decide to look at a career path in medical law & ethics, I know that this would be a quintessential case.

Thank you for listening to this episode of Chemistry Connections. For more student-ran podcasts and digital content, make sure that you visit www.hvspn.com.