Very Cool Compounds

Just as there are molecules that make your tongue tingle, there's a class of compounds that create a cooling sensation. Why, you might ask, would major companies all over the world invest lots of time and money into creating chemicals that simply make your skin or tongue feel cold?

 First, there's a perception among consumers that coolness equates to freshness and cleanliness so the appeal of these characteristics in personal hygiene products like toothpaste, shampoo, shaving cream, etc. is high. Consumers want gum, medicines, breath fresheners, and more that cool without being bitter, burning, stinging or tingling.

Secondly, flavor and fragrance companies are seeking less expensive means of creating this popular refreshing sensation, so a number of both natural and synthetic molecules have come "on the market." The more "natural" a chemical is the better: it's appealing to consumers and often less complicated to make. Cheaper production of either, however, allows flavor and fragrance businesses to compete with each other for contracts to industrial producers.

Finally, research is being done to find out which cooling compounds work synergistically with other ingredients to enhance or alter products for desired traits. A number of new cooling compounds have been created as a result of this research that also work as stand-alone cooling agents.

There is a wide variety of cooling products.

The two most important traits of a cooling compound are duration and intensity. The best ratio of these traits varies depending on the product. A minty gum, for instance, might require a burst of flavor when initially bitten but maintain a refreshing feel as long as it's being chewed. A body spray, on the other hand, might be intended to make the skin feel slightly cleaner at the moment of contact (versus oily or dirty).

The many different uses of cooling compounds makes the chemistry tricky. The amount of menthol needed to make the gum seem to burst with flavor would likely go unnoticed on the skin because cells in the mouth, and thus nerves, are more nearly exposed. Likewise, the amount of a cooling agent used to make the skin feel fresh would probably be bitter and disgusting if used in a piece of gum.

In general, cooling compounds have a hydrogen bonding group, a compact hydrocarbon skeleton, both hydrophilic and hydrophobic structural components, and a molecular weight between 150 and 350g/mol. Certainly, the hydrogen bonding and lipophilicity are the two most crucial components of a cooling agent. The industry's favorites have h-bonding groups that are hydroxy, n-alkyl carboxamides (for rapid cooling), sulfides, and phosphine oxides.

Carboxamide Functional Group

The lipophilicity is crucial as many cooling components are added to the flavor or fragrance oil and mixed before other ingredients are added. Since many liquid products such as sodas or alcoholic beverages contain theses chemicals, it's important that the cooling agent is in an easily miscible vehicle to prevent separation.

Hydrogen Bonding in Water

There are many, many of these cooling compounds so I'll detail just a few to give you an idea of the chemistry behind their design and the desired properties that they fulfill. 

Menthol and its direct derivatives are among the most common and oldest cooling compounds because of their "natural" sources in peppermint and cornmint oils. Although the naturally derived menthol is subject to price fluctuation due to crop success, it's still usually cheaper than fully synthetic menthol. Interestingly, the L-enantionmers are up to 45X more active than their D-menthol counterparts and the cooling effects of L-menthol can be detected on the skin in a solution with less than a 1% concentration.  Even at as low as 2%, the effects of menthol become "anesthetic" or "irritating" and at greater than 0.3 micrograms, say, in a piece of gum, it is irritating to cells in the mouth.

L-menthol is a ~45x more active cooling agent. 

Flavor and fragrance companies take potent and common chemicals such as menthol and toy around with them, hoping to achieve something more marketable. Takasago, for example, used the highly purified menthol isomer L-(-)-Isopulegol to make a specialty ingredient that "provides freshness, crispness, and coolness to citrus fragrances."They renamed it "Coolant P," a practice common throughout the industry to simplify long and often structurally confusing IUPAC names. The author says of one popular carboxamide:

“When called by its chemical name the structure is confusing, indeed a rather more sane chemical name would be N-methyl 2-isopropyl-2,3-dimethyl propionamide. In any event, it is sold by some companies as WS-23…” (p.219). 

Sometimes chemicals will be developed for specific industry purposes, such as the completely synthetic L-Monomenthyl  succinate. First reported by the British American Tobacco Co. in 1962 for use in manufacturing tobacco, this cooling agent was reported again in 1965 as a flavoring agent in cigarettes. The tobacco industry found this chemical desirable and worth further research because it is easily synthesized by a reaction of menthol with succinic anhydride. Its addition to cigarettes makes them taste less disgusting, presumably, and is intended to leave the smoker's mouth feeling…clean? 

Other cooling compounds are designed without a specific product in mind, but rather for their appeal to consumers as an ingredient. L-(-)-Monomenthyl glutarate, a.k.a. “Cooler 2," is "nature identical" meaning that it's exactly the same as a natural product, just created in a lab. International Flavors and Fragrances markets this as just that - nature identical - because the designation funnily enough lies in slightly higher esteem than "synthetic." 

There are a few cooling compounds that I recall actually having seen on ingredients labels before: mannitol, sorbitol, urea, methyl salicylate and camphor. Though not related to menthol, these compounds all have a sweet cooling character. What's really cool is that in mannitol, urea and sorbitol this effect is achieved through heat of dissolution. So, it's not just your brain being tricked into thinking it feels cooler, but there's an actual heat exchange occurring over the surface of the cell. Pretty neat.

The final category is what I like to think of as experimental cooling compounds. These are things that aren't actually on the market because they're potentially not safe or not perfected. AG-3-5 or "Icilin" is one such compound. Although it's a very potent cooling agent that is reported to create a refreshing sensation from the mouth all the way to the stomach, it's also a suspected mutagen. No big deal.

In short, there are a lot of cooling compounds used for a variety of business and chemical reasons. So, next time you're chewing a piece of gum, try to mentally separate the cool, refreshing feeling from the flavor itself. It's a pretty cool exercise and something I hadn't thought about before. Plugging your nose while taking the initial chews also helps make this distinction - you'll notice that your mouth feels cool and clean without experiencing the mintiness to the same degree. And there are actually panels of scientists who decide which cooling compounds achieve this sensation most successfully! What a job.

Next time on the Taste of Chemistry: Warming Compounds!

Ashley

Speaking of stinky breath: Bonus Video!

 





1 Rowe, David J (ed.) (2005) Chemistry and Technology of Flavors and Fragrances. Blackwell Publishing: Poole. Ch.9.^↩