The Two Scents of Limonene

The secret explaining how the two configurations of limonene smell is already in your hands.

The scent of oranges and lemons comes to mind when thinking about limonene, and although this is an apt descriptor, there is much more to learn about this molecule. The generation of limonene is often thought as one of the simplest biosynthetic reactions in the terpene world, yet this well-studied molecule has found applications as an anti-microbial, biofuel, household cleaning agent, and more. [1]

Limonene exists as two distinct conformations called enantiomers, identified as R and S. Enantiomers are molecules with identical atom connectivity that have two distinct three-dimensional confirmations. A useful detail to know is that one enantiomer is not super-imposable with its mirror image.

There’s an easy experiment you can do to help understand this. Place your left hand, palm down, on a flat surface and then place your right hand on top and align all the fingers on one hand with their respective counterpart on the other hand while maintaining both palms facing down. You can’t. The same happens with the R and S enantiomers of organic molecules such as limonene.

The oil extracted from orange peel of the sweet orange Citrus sinensis (L.) Osbeck is mostly composed of R-limonene (also called D-limonene), giving the fruit it’s distinct citrus scent, while S-limonene smells more like pine. [2]

In terms of medical applications, preliminary data show that limonene can protect cardiovascular tissue after myocardial infraction by reducing the damage done by reactive oxygen species. [3]

It might come as a surprise that the chemical precursor for both enantiomers of limonene is the same molecule, geranyl diphosphate (GPP). This single molecule is the precursor for most monoterpenes. [4] GPP is also involved in cannabinoid biosynthesis. In fact, without too much squinting, you can see what looks like a limonene molecule making up a significant part of cannabidiol.

The vast potential for chemical diversity in terpenes has led to the identification of over 80,000 members in the terpene family, many of which, like limonene, demonstrate useful applications in medicine and everyday life. As such, everyone could name a terpene even if they’ve never heard the term. For example, cholesterol is a type of terpenoid.

So, the next time you’re talking terpenes and limonene gets brought up, there’s a question that you need to ask: Which enantiomer?

References:

Vieira, A.J. et al. “Limonene: Aroma of innovation in health and disease.” Chemico-Biological Interactions, vol. 283, 2018, pp. 97-106. [Journal Impact Factor = 3.723; times cited = 21 (Scopus)]
Zhang, L.L. et al. “Antidepressant-like Effect of Citrus sinensis (L.) Osbeck Essential Oil and Its Main Component Limonene on Mice.” Journal of Agricultural and Food Chemistry, vol. 67, 2019, pp. 13817-28. [Journal Impact Factor = 4.192; times cited = 6 (Scopus)]
Durço, A.O. et al. “D-Limonene Ameliorates Myocardial Infarction Injury by Reducing Reactive Oxygen Species and Cell Apoptosis in a Murine Model.” Journal of Natural Products, vol. 82, 2019, pp. 3010-19. [Journal Impact Factor =3.779 ; times cited = 0 (Scopus)]
Gutensohn, M. et al. “Cytosolic monoterpene biosynthesis is supported by plastid-generated geranyl diphosphate substrate in transgenic tomato fruits.” Plant Journal, vol. 75, 2013, pp. 351-63. [Journal Impact Factor = 6.141; times cited = 57 (Scopus)]