Aspirin: The Pain Killer that Changed Medicine



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Essay D1

Professor James Whitesell

CHEM 151


Aspirin: The Pain Killer that Changed Medicine

More often than not people experience either some type of pain in their head or in certain regions of their body from normal to rigorous everyday activities. Obviously, the solution to metaphorically “kill this pain” is none other than a painkiller medication. The most common painkiller sold all over the world, and found in local drugstores, is aspirin.

The history of aspirin is theorized to date back to 3000 B.C. Mesopotamia. According to an ancient Sumer stone tablet from the Third Dynasty of Ur of medical text, the tablet mentioned willow-tree based remedies. Only, this tablet did not specify what these remedies were and if they were related to aspirin (5). It wasn’t until 1543 B.C. where the Ebers Papyrus, an ancient Egyptian medical text, mentioned willow and myrtle being used for remedies to treat pain, fever, and inflammation (5).Relative to these remedies of these time periods, aspirin’s main purpose is to relieve the pain and inflammation in the body caused by a variety of factors. The first person to document aspirin, as well as other compounds that relieve pain, was the scientist Hippocrates. He lived between 460 B.C. and 377 B.C. Hippocrates is often regarded as the father of modern medicine, because many of his methods of healing headaches, pains and fevers included making a powder that was made from the bark and leaves of the willow tree.

In 1828, several scientists studied this compound carefully for its pain healing properties. The community called it salicin. From that discovery, the active ingredient in salicin for pain relief was first isolated and recrystallized into a bitter tasting yellow, and needle-like crystal by a man named Johann Buchner. He was a pharmacy professor at the University of Muich. Arguably, two Italian scientists named Brugantelli and Fontana isolated the compound in 1826 and had recrystallized this compound first. Because their sample was very impure, it wasn’t considered to be isolated. From recrystallization and isolation came synthesis of this active compound. In 1829, Henri Leroux synthesized only 30 g of salicin from 1.5 kg of willow bark.

From salicin, a scientist named Raffaele Piria disassembled the compound into its sugar and aromatic component, in 1838. He converted the component into an acid of crystallized needles. These crystals in aspirin can be digested in the body in a much purer dosage. It is referred to on the back of the bottle of aspirin as salicylic acid (2). The only issue with salicylic acid experienced was that it was difficult for digestion, causing nausea and upset stomachs. In 1858, a scientist named Charles Frederic Gerhardt neutralized this acid by buffering it with sodium and acetyl chloride. This created acetylsalicylic acid.

Felix Hoffmann, a German chemist in 1899, used the reaction to produce the product and gave it to his father for pain relief. This lead to Aspirin being patented in 1900 by the Bayer Company. Aspirin is derived from the A (acetyl chloride), the “spir” in the name of the plant that derived salicylic acid, and the “in” as the familiar name ending in medicines. Since that time, Aspirin has been a major part of dealing with pain inside the body (2). But the question involved with this is how the Aspirin works inside the body.

Aspirin serves two main purposes to respond to pain inside the body. The first is to serve as an anti-prostaglandin (i.e. anti-inflammatory, fever-reducer, pain reliever). The second purpose is acting as a blood thinner, or an anti-platelet agent. All of these actions are required in order for Aspirin to act efficiently and safely in the body. Without the abilities to perform, aspirin’s side effects can lead to more pain or even death.

Prostaglandins are lipid compounds that are derived enzymatically from fatty acids. Whenever the body is injured in any way, prostaglandins are produced that cause the inflammation in that region of injury as part of the natural healing process. As a response, a small to excruciating level of pain is felt during the healing of the injury. Enzymes, mediators, and other cells like white blood cells facilitating that region cause this inflammation. One major enzyme involved with this inflammation is one called COX (i.e. cyclo-oxygenase). This enzyme is the one responsible for the formation of a group of inflammatory mediators known as prostaglandins (3). Aspirin inhibits the production of the chemicals in the body that cause the experience of pain by binding to the COX enzyme. The stomach digests the medicine, and the active ingredient is then expedited throughout the blood stream to the area of significant pain. This prevents swelling of the inflamed region and thus prevents the production of prostaglandins (4).

Not only does the medication prevent this pain from occurring, but it has also been discovered that it can actually lower the risk of heart attacks and even lower the chances og stroke. A heart attack is caused when blood flow is impeded in the body by blood clots in arteries or veins. With the COX enzyme, it plays a very important role in blood cessation. Blood clotting is a result of different functions caused by a variety of cells, especially platelets that are found within the blood stream. When blood vessels are damaged, these platelets clump together over the hole or vessel tear to facilitate repair. The COX enzyme not only facilitates production of prostaglandins, but also activates a chemical known as thromboxane A2. This chemical causes platelets to stick together to “plug” over the damaged area, also a type of inflammation process (3). The problem with this sometimes is that with the platelets clumping together, it can cause these platelets to form huge clumps, and then is some cases, can cause blood clots that can lead to heart attacks occurring. The thing about Aspirin is that it inhibits the enzyme activity done by COX, which leads to a reduction in the ability for platelets to aggregate. Aspirin’s inhibition properties can stop this process, but the bleeding still occurs (3).

The chemical formula of this molecule is C9H8O4. Although it is called aspirin as a medication, it is also known as either acetyl salicylic acid or by its IUPAC name, 2-Acetoxybenzonic acid. It is synthesized from salicylic acid and acetic anhydride with phosphoric acid and a catalyst to speed up the reaction. Not only is the process of synthesizing aspirin a long and tedious one, but also the reaction is actually a three-step process to ensure the effectiveness of the final product.



Figure 1. Synthesis of Aspirin



Figure 2. Separate reaction taking place to isolate remaining acetic anhydride and acetic acid and obtain aspirin.

In order to ensure the product will be effective, the aspirin must be isolated and then purified. Since aspirin is insoluble to a certain degree in cold water, while acetic acid and acetic anhydride (converted to acetic acid) are very soluble, the chilled solution is filtered and isolated multiple times (1). Acids help to wash the aspirin isolated, and assist with the purification process, before recrystallization. The crude sample of aspirin is then dissolved in ethanol, and then chilled. The sample is tested for the melting point, and compared to a purer sample of aspirin.

To ensure that the purification process will be higher yielding, manufacturers will synthesize the salicylic acid to ensure higher purity. To make salicylic acid, phenol and sodium hydroxide produce a sodium phenate. The strong base deprotonates the phenol and generates the salt and water shown below:



Figure 3. Generating a sodium phenate in water.



Exposure to CO2 (or dry ice) generates a sodium salicylate via a one carbon and one oxygen attachment to the ONa group on the 1-carbon position. As for the other oxygen, it attaches to the hydrogen donated from the water and then attached to the 2-carbon position. Then, addition of protons via sulfuric acid generates salicylic acid. This must be done carefully and cleanly as possible. From there, aspirin is then synthesized with the addition of acetic anhydride.

then

Figure 4. Generating sodium salicylate, the salt of salicylic acid, then protonation of the oxygen to create the acid

In today’s world of modern medicine and chemistry in general, aspirin stands as a prime example of advancement in medical treatments and as a prime example of chemical synthesis, reactions, and as a compound and molecules overall. Even though there is so much already discovered about aspirin, there are still many medical procedures being tested out. Outside of its known biological purposes, aspirin has been researched and developed to be a potential cancer curing agent (i.e. to significantly lower the risk of cancer occurring). And beyond possibly being able to fight cancer, it might even help with a multitude of different diseases in the future with further analysis and testing of the medicine. Just the multitude of what this medical compound is capable of makes aspirin one of the most interesting molecules that has changed the world.

Bibliography

(1) http://wwwchem.csustan.edu/consumer/aspirincons/aspirincons.htm

(2) http://inventors.about.com/library/inventors/blaspirin.htm

(3) http://www.aspree.org/AUS/aspree-content/aspirin/how-aspirin-works.aspx

(4) http://www.aspirin.com/scripts/pages/en/pain/html_how_does_aspirin_work.php



(5) http://www.medicalnewstoday.com/articles/161255.php

(6) http://www.aspirin-foundation.com/what/reactions.html


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