How the Organic Chemistry Behind Carbon-Hydrogen Bonds Changed the Medical Field

By: Alexander Heredia

A carbon-hydrogen bond, otherwise known as a C-H bond, is a specific bond between a carbon atom and a hydrogen atom. While it may not seem like much, this specific chemical bond can be found in many organic compounds, and is the key to many medications that are used in the modern pharmaceutical world. 

The Organic Chemistry Behind C-H Bonds

C-H bond activation is a series of mechanistic processes by which stable carbon-hydrogen bonds in organic compounds are cleaved [1]. Carbon-hydrogen bonds can be activated in multiple ways. These include: oxidative addition (increasing the oxidation state of the metal center by two), σ-bond metathesis (a chemical reaction wherein a metal-ligand σ-bond undergoes metathesis (exchange of parts) with the sigma bond in some other reagent [2]), and electrophilic substitution (a chemical reaction in which the functional group attached to a compound is replaced by an electrophile [3]).

A catalyst is a substance that increases the rate of a chemical reaction without itself undergoing any permanent chemical change. Catalysts are important parts of chemistry, no matter what you’re doing, whether it be titration or using sulfuric acid to make car batteries.

Because of the immense amounts of energy available by chemically catalyzing the C-H bond, C-H bonds are among the most powerful compounds in medicine and pharmaceutical products. An example of C-H bonding that has changed medicine is called Paclitaxel. Paclitaxel was created to combat many forms of cancer such as lung, ovarian, breast, and Kaposi sarcoma. Scientists used oxidative addition reactions to energetically activate necessary functional groups in specific areas on the taxane ring structure. This led to the creation of a powerful new drug that could prevent cancer cells from multiplying in one’s body; the compound formation of Paclitaxel.

Further C-H Bond Innovations 

Recently, a new method of activation for C-H bonds was discovered. Inspired by what human liver enzymes can do, Scripps Research chemists have developed a new set of copper-catalyzed organic synthesis reactions for building and modifying pharmaceuticals and other molecules. The new reactions are expected to be widely used in drug discovery and optimization, as well as in other chemistry-based industries. In their study, which was initially published on March 28 of this year in the renowned scientific journal Nature, the chemists showed that their new methods can be used to perform two modifications—called dehydrogenations and lactonizations—on a broad class of inexpensive starting compounds. The reactions require only a simple copper-based catalyst, whereas related reactions typically require much more cumbersome and expensive methods—though this specific type of reaction was previously inaccessible by any organic synthesis method [4]. In this approach, chemists use ligands and catalysts to disconnect a hydrogen (H) atom from a carbon (C) atom at a desired position on an organic molecule. This disconnection allows a new cluster of molecules, known as a functional group, to bond where the hydrogen atom had been. Most molecules used to build new drugs include rings of carbon atoms, also called carbo-cycles [5].

Summary View

Carbon-hydrogen activation is a key part of pharmaceutical and medicinal compounds. As more research, development, and testing are conducted, the potential progress C-H bond activation holds is immense.

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Author Alexander Heredia is an 9th grader from the Southern United States, specializing in biochemistry related research topics.

Works Cited

1. “C-H Activation Reactions” (https://www.mt.com/us/en/home/applications/L1_AutoChem_Applications/L2_ReactionAnalysis/c-h-activation-reactions.html#:~:text=C%2DH%20bond%20activation%20is%20a,0%2C%20C%2DC%20and%20C%2DN%20bonds.)

2. “Sigma Bond Metathesis” (https://chem.libretexts.org/Courses/Tennessee_State_University/CHEM_4210%3A_Inorganic_Chem_II_(Siddiquee)/07%3A_Organometallic_Reactions_and_Catalysis/7.01%3A_Reactions_Involving_Gain_or_Loss_of_Ligands/7.1.04%3A_Sigma_Bond_Metathasis)

3. “Electrophilic Substitution Reaction” (https://byjus.com/chemistry/electrophilic-substitution-reaction-mechanism/#:~:text=An%20electrophilic%20substitution%20reaction%20is,is%20typically%20a%20hydrogen%20atom.)

4. “New copper-catalyzed C-H activation strategy from Scripps Research” (https://www.scripps.edu/news-and-events/press-room/2024/20240419-yu-copper-catalyzed.html) 

5. “Crossing the ring: New method enables C-H activation across saturated carbocycles” (https://www.sciencedaily.com/releases/2023/05/230531150050.htm)