November phytochemicals - frankincense, ephedrine, and more!

Gallagic acid: a beautifully symmetrical precursor to complex ellagitannin phenolics in the rind, heartwood, and bark of pomegranate (Punica granatum). These compounds seem to inhibit carbonic anhydrases, metalloenzymes that interconvert water/CO2 and carbonic acid.

Olibanic acids: Relatively recently discovered, these compounds are from Boswellia sacra (Sapindales), the frankincense tree (https://bit.ly/2hncgHQ). These molecules give the odor of the tree’s dried resin a characteristic 'old church' note. Now that these compounds are known, genes underlying their biosynthesis can be discovered, and the frankincense odor could be replicated in engineered yeast - putting a stop to the unsustainable harvest of Boswellia trees.

Cucurbitacins: These bitter-tasting compounds are found in some types of pumpkin and squash (cucurbitaceae), mainly wild varieties. In high doses (e.g. from bitter zucchini) they can cause illness, even death(!), and are under basic research. Stay away from bitter squash!

Ephedrine alkaloids: Components of traditional Chinese medicine from Ephedra spp. (gymnosperm shrubs), these isomeric phenolics are stimulants and can increase blood pressure. Their diastereomers (pseudoephedrine) are less potent.

Myristicin: A compound from the evergreen Myristica fragrans, which is in of my favorite plant groups: the Magnoliales. This plant is the source of nutmeg (though myristicin is also found in the Apiaceae; dill, parsley, etc.). This phenolic compound is psychoactive at high doses - causing nausea and paranoia.

October phytochemicals - absinthe, aspirin, and more!

Honokiol: a polyphenol lignin antioxidant from the bark and cones of Magnolia spp. A traditional medicine whose hydrophobicity facilitates crossing the blood-brain barrier (thus bioavailability) where it exerts various phamacological effects.

Thujone: a bicyclic monoterpene from wormwood (the aster Artemisia absinthium) and many other plant species. It is a GABA agonist that can cause muscle spasms and convulsions (it is dangerous!). Historically used in the making of absinthe, but does not seem to be psychoactive. It is apparently still unclear what (if any) psychoactive ingredient is present in absinthe

Salicin: a glycosylated salicyl alcohol - responsible for the anti-inflammatory and pain relief effects of willow bark (Salix spp.) and in part for the effects of castoreum (if you haven't looked up castoreum - you should). It has been used since hundreds of years BC, and inspired modern aspirin - reacting salicylic acid with an acetylating agent gives the acetyl salicylic acid that is used the world over.

Labdane: historically harvested as incense (mentioned in Genesis?) by brushing labdanum resin from Cistus ladanifer (Malvales). It was also harvested by brushing the legs of livestock (sheep and goats) that had been brushing against Cistus bushes. A precursor to bioactive and scented terpenes in both gymno- and angiosperms, labdanes are still used in permumes today.

The taste and aroma of saffron

Worth more than their weight in gold, saffron crocus (Crocus sativus, Iridaceae) stigmata produce the glycoside picrocrocin and its aglycone saffranal (products of zeaxanthin degradation?) - major contributors to the taste and aroma of the "king of spices".

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Sassafras

This week: safrole. Though found in small amounts in anise, cinnamon, and nutmeg, it's a major component of sassafras oil. It has a characteristic "candy shop" scent, is a synthetic precursor to MDMA, and is evidently banned from use in food by the FDA.

Figure 1: Sassafras albidum - the sassafras tree - oil from which contains safrole, an interesting plant chemical.

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Amorphophallus titanum and the essence of rotting fish

Have you heard of the corpse flower? Scientifically known as Amorphophallus titanum, the corpse flower gets its name because it generates a variety of malodorous compounds to attract animal pollinators. Among these is trimethylamine, or "essence of rotting fish" (Fig. 1), a biomarker used by fish freshness detectors.

An excellent short video here on these compounds and the ability of the corpse flower to generate heat!
The chemistry of the corpse flower's stink - Bytesize Science

Figure 1: The flowers of Amorphophallus titanum generate, among others, the smell compound trimethylamine, which smells like rotting fish.

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An ancient hemlock poison

Figure 1: Conium maculatum, commonly known as poison hemlock, produces a toxic alkaloid called coniine, which was supposedly the downfall of Socrates himself.

Have you seen a plant lurking in alleyways (or in some backyards!) whose leaves look a bit like those of carrot but a bit bushier? There is a good chance that such a plant is actually Conium maculatum - a poisoner that has been used by humans for centuries: poison hemlock. This plant produces a compound called coniine, an alkaloid (a nitrogen-containing molecule) that causes respiratory paralysis in many mammals. Poison hemlock contains substantial amounts of coniine in its leaves - a handful of leaves are enough to kill. This is particularly problematic for farmers who's livestock can unwittingly eat hemlock if it is in their grazing area. Coniine also seems to have played an important role in history - it was apparently used to kill condemned prisoners in ancient Greece, and seems to have been responsible for the death of Socrates himself - an event reported by Plato that has since been the subject of a famous oil painting. It is amazing that such a simple, small molecule has such a rich history.

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Citronellal - natural bug repellant

Have you ever burned a citronella candle to ward off annoying insects? Where do those come from and how do they work? These candles are often made using citronella oil - the essential oil from citronella grass, or Cymbopogon nardus. This oil is used extensively in soaps, perfumes, cosmetics, and of course candles. Interestingly, citronella grass is a cousin (same genus, different species) to lemongrass Cymbopogon citratus, used in teas and some recipes.

Inside citronella oil are several different chemical compounds, the most common of which is an aldehyde called citronellal (Fig. 1). This compound is a major contributor to the anti-insect and anti-fungal properties of citronella oil. When candles contain this oil, the heat from the flame helps the citronellal evaporate into the air - creating a bug-repelling zone all around the candle.

Figure 1: The grass Cymbopogon nardus, also known as citronella grass, produces oil that contains citronellal, a natural insect repelling compound.

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Monolignols - Happy Arbor Day!

Happy Arbor Day from Nebraska! Today let's have a look at monolignols, simple ring molecules that when combined together make one of the strongest and most abundant biopolymers on Earth - wood.

Do you remember learning in school that the mass of a plant doesn't come from the soil, but from the air? Perhaps this tidbit is easy to forget, but it's true! Plants can suck carbon dioxide out the air and turn it into sugar. They use this sugar as energy to grow and reproduce. In order to stand up and reach for the sun, plants need to be able to build rigid structures can can hold weight. Trees are wizards at doing this.

Figure 1: The monolignols p-coumaryl alcohol, coniferyl alcohol, and sinapyl alcohol. In the background, an example of a lignin polymer.

To build rigid structures, woody plants break down the sugars they obtained from capturing sunlight and reassemble the carbon pieces into monolignols - ring structures made of carbon, oxygen, and hydrogen. Some of the most common monolignols are p-coumaryl alcohol, coniferyl alcohol, and sinapyl alcohol (Fig. 1). Scientists suspect that the trees then produce enzymes (small molecular-scale machines) that can assemble these monolignols use what's called (I kid you not) 'radical' chemistry. Radicals are the technical name for unpaired electrons. In an unpaired state, electrons are highly reactive and it seems that it is this energy that the tree's molecular machines use to link the monolignols together.

After radical polymerization, very large polymers are formed - see the background in Fig. 1. This process consumes an incredible amount of carbon. In fact, the Carboniferous Period (350 - 300 million years ago) is in part defined by plants' evolution of the ability to sequester carbon from the atmosphere and store it in a way that allows them to stand up tall. It is these huge, cross-linked polymers that give wood its strength, and it is these same structures that are oxidized during the burning of wood, returning the carbon to the atmosphere after potentially hundreds of years in storage.

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The periwinkle's deadly secret

Figure 1: The vinca alkaloid vincristine from the periwinkle Catharanthus roseus.

Periwinkle, the common ornamental plant, is highly toxic because of the chemical compounds it contains. One of these compounds is called vincristine - a compound that can prevent mammalian cells from dividing. This compound contains nitrogen atoms, making it an alkaloid. Vincristine and its sibling alkaloid, vinblastine, both inhibit cell division which makes them effective chemotheraputics. They are used to treat several types of cancer. For the plant, these compounds constitute a defense mechanism: if eaten in quantity, periwinkle leaves are highly toxic. So, even though the periwinkle is a pretty plant to look at - it's not good to eat!

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Limonene - oil from citrus peels

Figure 1: Orange peels and limonene. The peels of oranges contain oil. This oil is mostly made up of limonene. On the right: D- and L- limonene; mirror images of each other, but with very different properties.

Have you ever used a citrus degreaser? How does that stuff work? It turns out that the peels of citrus plants contain oil! Not the slimy black stuff that comes from million-year-old compressed algae, but a much fruitier substance. The majority (~90%) of orange peel oil is made up of a compound called limonene. This compound has a duality to its nature that is very important. Think about hands: there are left hands and right hands, which, though they are made of the same parts (four fingers, a thumb, and a palm), are not identical. Rather, hards are mirror images of each other. Limonene is just the same – there is a “left” limonene and a “right” limonene. In chemical language, these are called D-limonene and L-limonene. Our noses are particularly tuned to the difference between these two: D-limonene smells like citrus, while L-limonene smells like pine or turpentine. Limonene is used extensively in the perfume industry, as a component of degreasers, as a natural insect and pest deterrent, and even as a building block for renewable, biodegradable plastics [1]. Fantastic!

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[1] Alternating Copolymerization of Limonene Oxide and Carbon Dioxide. Christopher M. Byrne, Scott D. Allen, Emil B. Lobkovsky, and Geoffrey W. Coates*. Journal of the American Chemical Society 2004 126 (37), 11404-11405 https://pubs.acs.org/doi/abs/10.1021/ja0472580.

Nightshade

Figure 1: Mandragora roots (artist's rendition). The roots of Mandragora species contain hyoscyamine and scopolamine, tropane alkaloids with similar structures, but very different psychoactive effects.

Nightshade. The name conjures fear in many of us… but why? The nightshade family of plants is also called the Solanaceae. Some members of this family produce chemical compounds that are psychoactive in humans (though other members of the Solanaceae are important domesticated food crops, i.e. tomatoes, potatoes, eggplants, etc.). One member of the nightshade family is the Mandragora genus. These plants are also called mandrakes, and truly have roots that look like small humans. Alcoholic extracts from these plants contain hyoscyamine and scopolamine. Hyoscyamine is a central nervous system stimulant, but scopolamine (which differs only in that it contains an additional oxygen atom), is a central nervous system depressant. Plants containing these two compounds have been used for centuries as drugs, poisons, and aphrodisiacs - they appear in Homer’s Odyssey and works by Shakespeare. What would these icons have thought if they had known the uniqueness of these two compounds to the nightshade family and the subtleties of their structures and functions?

Arsenic can't kill this fern!

Have you ever seen the greenish hue of treated lumber and wondered what it was? In some cases this color comes from chromated copper arsenate, which has been used since the 1930s as a wood preservative. While this preservative has been studied extensively and appears to be safe, the process by which it is applied can lead to arsenic-contaminated soils. Dr. Lena Ma of the University of Florida was walking around a disused wood treatment site one day when she notice a particular species of fern growing all around the site. By bringing some fronds (a fern's leaves) to the lab, she discovered that this fern, Pteris vittata (Figure 1), is able to accumulate 200 times more arsenic than is present in the surrounding soil! This was an incredible finding, because arsenic is very famous for being lethal to living organisms.

Figure 1: Pteris vittata. This fern sucks arsenic out of the soil (or walls!) in which it grows and can hyper accumulate the arsenic in its fronds (leaves).

Arsenic is a quasi-metal substance called a metalloid, meaning that it exhibits some metal-like properties (it can form alloys with other metals), but also some properties of non-metals (it is brittle). It is also chemically similar to phosphorous, an element that is a component in many important components of all of Earth's organisms, such as DNA and RNA. Since arsenic is similar to phosphorous (it is in the same column in the periodic table), it can sneak into living organisms through phosphorous transporters, then interfere with all the essential cellular processes that require phosphorous. It is this interference that makes arsenic so toxic, and why the ability of the Pteris ferns to hyper-accumulate arsenic so amazing.

Intrigued by this arsenic-tolerant fern, Dr. Ma and her colleagues carried out further research on Pteris vittata. They soon found that when this fern grows in healthy soils it does not have such high levels of arsenic, but if arsenic is added the fern rapidly absorbs the arsenic through its roots and stores it in its fronds. After further study, scientists discovered that these ferns seem to have new versions of phosphorous transporters that, instead of moving phosphorous, can selectively move arsenic and quarantine this metal in a special plant cell storage container called the vacuole. It seems likely that this fern does this to poison any animals or insects that attempt to eat it.

Naturally, Pteris vittata (and its relatives that also hyper-accumulate arsenic) have great potential in bioremediation - the use of biological organisms to clean up a polluted environment. Perhaps these ferns could be grown in poisoned landscapes to soak up the arsenic and then be removed and disposed of safely. This is important for all humans since arsenic in soils makes its way into our food and water, causing illness, cancer, and death in high doses. Efforts are underway to see whether what we have learned about Pteris arsenic tolerance can be applied to creating crops that will be able to prevent arsenic from entering their roots via phosphorous channels, thereby reducing the amount of arsenic in our diets. It is fantastic to learn such an important biological tactic from a fern. Ferns have been on earth longer than all animals and insects, and have clearly developed some tricks during this period - only time will tell what other wisdom they may share with us.

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For more, see: https://www.nature.com/articles/35054664 http://www.nature.com/news/2004/040512/full/news040510-4.html