Click Chemistry: The Simple Science That Changed The World

                               Click Chemistry 

         How could a straightforward chemical reaction revolutionize the entire field of chemistry? After all, wouldn't it be a complex and large-scale reaction to make an impact? In the case of click chemistry, the exact opposite is true. Click chemistry is popular purely for its simplicity, reliability, and versatility.

In 2001, chemist K. Barry Sharpless published a research paper detailing a theoretical process that he referred to as click chemistry. In simple terms, click chemistry is the process by which simple molecules that bond well together come together to form a more complex molecular model. To put it into perspective, imagine puzzle pieces. Each puzzle piece corresponds perfectly to another piece. These pieces do not need to be forced together, and by attaching them correctly, side issues do not occur. The same applies to click chemistry. Just like puzzle pieces, molecules find their perfect match and become fitted together. They are flawless matches because they come together smoothly and do not produce side effects. They only produce the desired result. When click chemistry was discovered, it made a significant impact in the chemistry field, especially in drug discovery, bioconjugation, and materials science for a variety of reasons. Click chemistry was clean, efficient, and quick—qualities that were essential in chemistry and could seriously make an impact in every form of science. As opposed to traditional synthetic chemistry, which was usually step-abundant, uncertain, and produced side effects, traditional synthetic chemistry often faced multiple side effects that were harmful to the experiment and had to be done under extreme conditions over a long period. Click chemistry could be done under mild conditions quickly and without harmful effects. Through click chemistry, scientists could easily conduct chemical reactions with simplicity and without using valuable resources.

    However, after this paper was published, Sharpless discovered a reaction that sparked the powder keg for his research. This reaction came to be known as Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). That's quite a bit of jargon, so to simplify, let's break it down. First off, Copper(I)—simply means that the reaction was catalyzed by copper or that the reaction was sped up by the addition of copper. The (I) shows the oxidation state of copper, which is +1 in this case—meaning each copper ion has lost one electron. Next, we can discuss what azide-alkyne is. These are the molecules in the reaction that both contain specific properties. Azide is a molecule with three nitrogen atoms (N₃⁻) drawn as N⁻=N⁺=N⁻. It is a unique structure that is incredibly reactive and unstable. These dashes represent how many of the electrons are connected. Because the overall molecule looks like this: N-N≡N, it has a unique structure that not only makes it incredibly weak but also very reactive. This is where the second molecule comes in, the alkyne. An alkyne is a hydrocarbon containing at least one triple bond between carbon atoms (C≡C). In the CuAAC reaction, a terminal alkyne is often used, which has the structure H–C≡C–R, where R represents the rest of the molecule and works as a modifier without affecting the reaction. The terminal alkyne is particularly reactive due to the hydrogen atom at the end of the chain, which facilitates the reaction. These two molecules bond extremely well together due to them both being reactive. However, the triple bond for the carbons in this molecule is quite strong, and the molecule needs a higher activation energy (the energy essential for molecules to bond) to bond with the azide, as it is not reactive enough. This is where the copper comes in. Copper works as a catalyst because it coordinates with the alkyne and changes its electron distribution, lowering the activation energy required to combine with the azide. This weakening allows for the reaction to go quicker and smoother. The (I) is essential due to its specific properties, which help change the shape and electronic properties of the alkyne and make it more reactive. Finally, we have to discuss cycloaddition. A cycloaddition is a type of bond where two molecules come together to form a ring structure. In this specific reaction, the two molecules, alkyne and azide, form a five-membered ring called a triazole.

    This reaction wasn’t given its honor until 2022, when K. Barry Sharpless received his second Nobel Prize, going down as one of the only people in history to win two Nobel Prizes. Along with him, scientist Morten Meldal also won the prize for this discovery. While they were not research partners, they conducted similar independent research separately and came out with similar reactions. Since then, click chemistry has only grown. Because of its usefulness and efficiency, scientists from the entire chemical field have been eager to apply it to their specific field or spark a reaction close to it. However, click chemistry is still rare and developing, and it still has a long way to go.

    

    This topic immediately fascinated me. I have seen numerous articles discussing it, and the chemistry community seems to be fixated on click chemistry. The thing that fascinated me was how a reaction that was made to have a simple and precise outcome is so incredibly difficult to achieve. This idea was unheard of a few years ago, and now scientists obsess over it daily. It has made such a large impact simply because of how efficient it is. It is mind-boggling to think how uncertain chemistry is, that a reaction like that is so precise is entirely new. It is also extraordinary to think how many different chemical fields this reaction can apply to. It is astounding, and I hope to gain more insight into it in the future.

    In conclusion, click chemistry has been an incredibly beneficial part of chemistry in recent years. Since it was discovered with the CuAAC, it has sparked deep interest in the chemical field. Although the Nobel Prize for this discovery was awarded only three years ago, scientists have explored this reaction to its depths and applied it to many fields. This is amazing, and shortly I hope to discuss more about this reaction. I apologize for any incorrect data within this blog, as I did not have enough time to dig as deep as I would have liked, and I deeply appreciate any critiques I can gain from others. However, I hope you enjoyed this anyway and hopefully learned something new. To end this blog, I have a question: What heights do you believe click chemistry will reach in 10 years from now? Thanks for reading, and see you next week!