The Aztec Alchemist

Molecule of the Week #4 - Ibuprofen

2011-06-13T01:14:00.000+02:00

This week's molecule, ibuprofen, has been a lifesaver for me in the last few weeks. Ibuprofen is a nonsteroidal anti-inflammatory drug that is used to relieve pain and fever (1), and so I have employed it to relieve joint pain during my adventures in half-marathon training and to relieve some amazing stress-induced headaches during the final push to finish my Ph.D. in organic chemistry.

A bottle of generic-brand ibuprofen.

One interesting bit of information about ibuprofen is that its synthesis is a great example of green chemistry (2). Previously, the synthesis of ibuprofen was rather lengthy (over five steps) and would generate a significant amount of waste. Now, the synthesis of ibuprofen consists of three steps and exercises atom economy in that a high percentage of the reactant atoms end up in the desired product and a low percentage of the reactant atoms contribute to the formation of waste products (3). The development of this improved synthesis was given the Presidential Green Chemistry Challenge Greener Synthetic Pathways Award in 1997.

The chemical structure of ibuprofen.

References
1. Arch. Int. Pharmacodyn. Ther. 1969, 178, 115-129.
2. Green Chem. 2005, 7, 121-128.
3. Pure Appl. Chem. 2000, 72, 1233-1246.

Molecule of the Week #3 - Caffeine

2011-04-25T17:34:00.001+02:00

Caffeine

This week’s cool molecule is one that is close to my heart, especially because I am using it in industrial quantities so that I can finish writing my Ph.D. thesis within the next couple of weeks. I am, of course, talking about caffeine.

According to legend, its discovery goes something like this:

A young Ethiopian goatherd observed that his goats would jump and frolic with unusual exuberance after eating the bright red berries from a local plant. Curious, he decided to try the berries himself, and was surprised to find himself completely alert and invigorated. Excited about his findings, he went to a nearby monastery to share the berries with the holy men there.

From left to right: Unroasted coffee beans from Ethiopia, roasted coffee beans, and brewed coffee.

After listening to his story, the holy men immediately declared the berries to be a temptation from the devil and cast them into the fire. What none of them expected was the heavenly smell that would emerge from the flames a few moments later. The holy men were forced to admit that perhaps they had judged the berries too hastily and that perhaps they were a divine gift. They took the now-roasted coffee out of the fire and put it in water, thereby making the world’s first cup of coffee.

As a coffee enthusiast, it is a story I have read many times. I was also pleasantly surprised to hear this story from Ethiopians when I visited Addis Ababa last fall.

Coffee ceremony in Addis Ababa, Ethiopia.

Centuries after this legend takes place, German chemist Friedlieb Ferdinand Runge isolated coffee’s active compound and, appropriately, named it caffeine (1). Interestingly, the beans from which Runge isolated caffeine were given to him by none other than literary golden boy Johann Wolfgang von Goethe (2). In the years immediately following Runge’s discovery, other scientists also isolated this iconic compound from tea and yerba mate.

Structure of caffeine.

Caffeine is a small and hydrophobic molecule that belongs to the xanthine family, which is structurally similar to the purine bases in DNA. Other members of the xanthine family theophylline (sometimes used in the treatment of asthma) and theobromine (found in chocolate).

Due to its size and hydrophobic properties, caffeine can easily cross the blood-brain barrier and directly affects the central nervous system (3). The brain is a complicated organ, and there have been multiple explanations why caffeine is such an effective stimulant. One of the most appealing explanations is that caffeine acts as a nonselective antagonist for adenosine receptors in the brain; that is, when caffeine binds to these adenosine receptors, it blocks adenosine from doing the same.

One reason why the above explanation is so appealing is that addition of adenosine to brain tissue has been shown to produce effects that are the exact opposite to those of caffeine, like depression of spontaneous electrical activity in neurons and inhibition of synaptic transmissions. Furthermore, drugs that increase adenosine concentrations in the blood (and thus presumably in the brain) have side effects that include lethargy and drowsiness (4).

Also, it is simple to see why caffeine could fit so well in the adenosine binding site: adenosine is constructed from a sugar molecule and an adenine molecule. Adenine is a purine base, and thus structurally similar to caffeine (4). They are so similar that my science-fiction addled brain creates rather elaborate fantasies where, upon sufficient consumption of coffee, all of the adenine bases in my DNA are replaced by caffeine molecules, transforming me into a mutant with awesome superpowers.

A comparison of the structure of a) caffeine and b) adenosine.

In sum, caffeine is a fascinating molecule that can affect our brains, giving it the power to help us achieve acceptable levels of alertness and productivity despite not getting nearly enough sleep the night before. This property, together with its delightful taste in beverage format, either as tea or coffee, has given it an important cultural status worldwide that few other molecules have achieved.

References:

1. Angew. Chem. 1935, 48, 1-40.
2. The World of Caffeine; Routledge: New York, 2002.
3. Pharm. Rev. 1999, 51, 83-133.
4. Brain Res. Rev. 1992, 17, 139-170.

Molecule of the Week #2 - Quinine

2011-04-10T19:31:00.001+02:00

In the northern hemisphere, spring is advancing and the weather is slowly growing warmer. Flowers are blooming, bees are buzzing, and cute baby animals abound. It's the perfect time for even a stressed-out Ph.D. student to leave the lab and enjoy a nice picnic in the sun with friends.

Despite its many wonders, spring also brings with it my arch-nemesis: the dreaded mosquito.

And this made me think of quinine, this week's awesome molecule.

Why?

Quinine can be used as a pain-killer (1) and as a fever-reducing (although this is debatable, 2) drug. Most importantly, and the reason why mosquitoes made me think of it, quinine has been the primary treatment for malaria for centuries (3).

The Structure of Quinine.

Due to its bitter taste, people who had to consume quinine resorted to dissolving it in slightly sweetened water. Hence the birth of tonic water. And, since people still found the taste of tonic water rather unpleasant, they resorted to diluting tonic water with gin. Hence the birth of gin and tonic.

Why do I mention this?

Besides its many medicinal uses, quinine has one additional delightful property: it's fluorescent! In fact, it was one of the first fluorescent molecules studied in depth (4). So... next time you fancy a gin and tonic, bring a UV lamp!

Commercial Tonic Water under a UV Lamp.

References:
(1) J. Pharmacol. Exp. Ther. 1943, 77, 184
(2) a) Acute Pain 1997, 1, 33; b) T. Roy. Soc. Trop. Med. H. 1995, 89, 197.
(3) J. Am. Chem. Soc. 2001, 123, 3239.
(4) Principles of Fluorescence Spectroscopy 3rd Ed; Springer: New York, 2006.

Molecule of the Week #1 - Capsaicin

2011-04-02T00:48:00.003+02:00

This week I would like to introduce you to one of my oldest friends: capsaicin, the fun molecule responsible for the spiciness in chili peppers.

Chili Pepper

A fun fact about capsaicin is that it affects mammals but not birds... Birds are capable of spreading the seeds of the chili pepper plant, while mammals cannot. Furthermore, mammals can destroy the seeds by chewing, thus rendering them useless. It makes sense that capsaicin would be used by the plant as a mammal repellent.

Capsaicin has demonstrated some anti-microbial properties. There are also claims that capsaicin has anti-fungal properties (1) and that it can be used in the treatment of some types of arthritis (2) and cancer (3).

It is a solid that melts at 68˚C and it is only very slightly soluble in water. Although in small amounts it adds a kick to boring food, capsaicin as a pure substance can be rather toxic (LD50 in mice is 190 mg/kg) (4).

Capsaicin

To test the wonderful properties of capsaicin, and to combine my love of chemistry with my love of food, I decided to perform a little experiment:

Hypothesis: Would a bowl of super spicy chili get rid of my cold and sore throat?

Materials: Onions (1 large) , carrots (1 large), garlic (2 cloves), bell pepper (1 large) canned tomato chunks (800 g), ground beef (500 g), kidney beans (800 g), sweet corn (400 g), arrabbiata tomato sauce (500 mL), Thai chili peppers (10 small), Dave’s Insanity Sauce (5 mL), dry jalapeño powder (1 tsp), red chili pepper powder (1 tsp).

Procedure: 1) Make chili. 2) Consume chili.

Results and discussion: The chili that resulted from this recipe was spicy to an esophagus-melting degree. My cold isn’t gone, but my sore throat feels better. Whether that is due the spice-induced numbness or due to capsaicin’s anti-microbial properties is uncertain. Further testing is required.

References*:

(1) Int. Biodeterior. Biodegrad., 2008, 4, 364.

(2) Clin. Ther. 1991, 13, 383.

(3) Biochim. Biophys. Acta 2007, 1773, 565.

(4) Capsaicin MSDS

* Disclaimer: These references are stuff that I found and read for fun. It does not mean that I agree 100% with them or that they should be taken as law.

Molecule of the Week

2011-04-02T00:20:00.000+02:00

2011 is the International Year of Chemistry. As a good little chemist (and as a good little science-enthusiast in general), I intend to celebrate the IYC by posting fun facts about noteworthy molecules every weekend. Enjoy!