My grandfather was a big fan of the old sitcom Hogan’s Heroes, and to some extent, I’ve inherited his taste in comedy. The episode which sticks out in my mind the most, centers around a heavily guarded barrel of water. Numerous rumors circulate about why the barrel of water is so important, including one that the water is from the Fountain of Youth, but eventually it is revealed that the barrel simply contains “heavy” water. Prior to my days as a student of chemistry, this begged the question: what makes the water so “heavy”?
You may be aware that a molecule of water consists of three atoms: two hydrogen atoms and one oxygen atom. Water becomes “heavy” when the hydrogen atoms in water are substituted with a rare isotope of hydrogen. In case you’re not familiar with isotopes, you can think of isotopes as being the same basic building blocks of a molecule, only with a tiny bit of extra mass. This brings me to our main topic of discussion: deuterium.
Both deuterium (D) and hydrogen (H) consist of one electron and one proton, but deuterium also has a neutron, which is what provides the extra mass in heavy water. More succinctly, it can be said that deuterium is an isotope of hydrogen. This subtle subatomic difference is all that distinguishes heavy water (D2O) from regular water (H2O), but the unique properties of D2O permit a myriad of applications in chemistry and physics. The most sobering of these applications is its role in the production of nuclear weapons, thus the ironic reason for its appearance in Hogan’s Heroes.
However, deuterium has many applications beyond its use for nuclear purposes. Heavy water is a common laboratory solvent for experiments in chemistry, but deuterium can find other uses in basic research as well. At Indiana University, the Thielges lab exploits the subtle difference between hydrogen and deuterium for an area of research with a more biological twist, specifically concerning proteins.
The study of proteins and peptides – large biomolecules which are the workhorses of living cells – at the molecular level often involves labeling the protein or peptide of interest with a small molecular “probe”, which provides the signal for a biophysical or analytical technique. Unfortunately, the probe can perturb the biomolecule’s structure, thus leading to artifacts in the experimental results. The Thielges lab completely circumvents this concern by incorporating deuterium in a site-specific manner to form a carbon-deuterium bond (C-D) which serves as a non-perturbative probe for infrared spectroscopy. Since hydrogen and deuterium differ only by one neutron, this approach is a significant improvement compared to probes which involve the addition of many atoms to the biomolecule of interest.
In particular, the Thielges lab has used these deuterium probes to study the SH3 domain, which is a specific structural motif found in many eukaryotic proteins, including human proteins. SH3 domains act as ‘molecular recognizers’ — their specific structure and motions recognize other segments of proteins, kind of like finding a compatible dance partner, in the cell and body. A study in the Thielges lab incorporated carbon-deuterium probes into one particular peptide and revealed that the peptide adopts multiple distinct conformations when bound to its partner SH3. Excitingly, these conformations had not been previously distinguishable. In this way, something as simple as a change in isotope propels fundamental research towards a better understanding of the complex molecular machinery which makes up our cells.
To add one more brief story to this diverse (but nowhere near complete!) assortment of applications for deuterium, the pharmaceutical industry is currently trying to obtain FDA approval for deuterated drug molecules. One theoretical advantage to swapping out an H for a D atom on your drugs: the body (or more specifically, enzymes in the body) has a harder time breaking them down. Thus, it may be possible to achieve the drug’s desired effect with a lower dose. One complication that will likely slow down the advance of deuterated drugs into the pharmacy are legal battles over who gets to profit from the conceptually simple H to D switch on an existing drug.
A subtle change in the tiniest atom on the periodic table – the addition of one neutron to an atom of hydrogen – has ramifications which extend across many fields in scientific research. Deuterium may not provide us with eternal youth, as the characters of Hogan’s Heroes discovered empirically, but it has great value in nuclear power, drug development, and even some of the fundamental protein research at IU.