November 23, 2014

You Said Polar?

Alexis St-Gelais - Popularization

Polar: I am not reffering to the winter cold that has settled around here in Saguenay a few weeks ago... I am rather speaking of a concept that can be helpful to understand many chemical phenomena, to which I will certainly plentily refer to in the future on this blog. Polarity can indeed help to predict and explain the separation of molecules, their extraction, their volatility, their compatibility, and even some of their biological properties!

When atoms form chemical bonds, they do not share their electrons equally. Indeed, some elements attract electrons with more strength than others: they are more electronegative. The electrons are therefore more "concentrated" on one side of the bond. This in turn generates a slight difference in electric charges between the two sides, one becoming positive and the other negative. The more marked the difference is, the more polarized the bond becomes.

The four most frequent elements in natural organic molecules are ranked as follows, from the most to the least electronegative: oxygen (O) is the more electronegative, followed by nitrogen (N), and carbon (C) and hydrogen (H) are roughly equivalent. Of course, several other elements may be included in natural molecules, but they can introduce peculiar cases which I will not discuss now.

A C-H bond is relatively well balanced electronically, and the C-C bond features a perfect share of electrons. These bonds are nonpolar. Conversely, the O-H, O-C, N-H and N-C bonds imply the concentration of electrons on the O or N side, and are therefore polar. Figure 1 visually shows how this translates.
Figure 1. Approximate polarity schemes for a series of closely-related molecules. On isopropanol, the black arrow indicates the direction of the strong attraction of the electrons. The white arrows indicate a secondary attraction generated by the electron deficit in turn created at the CH. For all molecules, the red areas are rich in electrons, and thus partially negatively charged. The green areas are rather depleted of electrons, and thus slightly positive. Light gray indicates an electrically neutral region and dark gray a slight positive bias due to the positive charge of the neighboring atoms. BP: Boiling Point. 
Why is it useful to be able to get an idea of the polarity of a molecule? Figure 1 already gives a part of the answer by showing the boiling points of the molecules. You can notice that the more the molecule is polarized, the more the boiling point increases. This is because the polar molecules behave somehow like magnets: they possess two poles, which can attract the opposite pole of opposite sign on the neighbouring molecule. Thus, polar molecules tend to be very strongly retained to each other, so we must input a lot of energy to disrupt the intermolecular attraction, for example to enter the gas phase. Conversely, non-polar molecules do not attract eachother a lot. It is thus easier to induce a phase change. The same generally holds for the melting point.

This first property provides an excellent explanation for a phenomenon that we have discussed earlier for the analysis of essential oils. In general, in our tests, monoterpenes are eluted before the oxygenated monoterpenes, and sesquiterpenes before oxygenated sesquiterpenes. This is quite normal: molecules without oxygen are generally more volatile, given a similar molecular weight, than oxygenated molecules, because they are less polar. They therefore pass through the tubular columns at a lower temperature, and are detected earlier.

The polarity also helps to explain why essential oil and the water used to extract it form two distinct liquid phases. Indeed, in chemistry, "like dissolves like": polar environments easily mix together, and apolar media exclude polar media. Terpenes are composed mainly of non-polar C-C and C-H bonds, while water is highly polar. Therefore, the two groups reject each other and form non-miscible phases. In this regard, the essential oil has the same behavior as liquid hydrocarbons derived from petroleum and vegetable oils: all three groups feature molecules with a high proportion of non-polar bonds.

I also mentioned that polarity influenced the separation of molecules. Get a quick look back at my post about the basic principles of chromatography. The affinity which I was referring to in that text is often based on polarity. For example, solid silica, often used in chemistry to separate extracts, is a very polar material due to its silanol groups (Si-OH). It therefore retains strongly polar compounds, and only poorly non-polar compounds. A quick estimate of the polarity of a molecule allows the chemist to more easily target the chromatographic technique to use, and the conditions to be employed.

Finally, polarity affects how molecules interact with your body... Blood, lymph or cellular content form polar aqueous media. In contrast, cell membranes, skin, liver or fat cells, for example, are very rich in lipid derivatives and proteins exhibiting low polarity. This creates a wide range of possible interactions. For example, polar vitamins (B and C), which are water-soluble and can easily be excreted in urine, hardly ever cause overdoses, unless one takes huge amounts within a short period of time. In contrast, low polarity vitamins taken regularly in excess will accumulate in the environments for which they have affinity, including fat. They can then lead to hypervitaminosis (usually with vitamins A and D) with potentially serious, although rare, effects.

Another example: cosmetic creams are often made of a basis of molecules that are moderately to weakly polar, with a creamy or greasy texture, in order to penetrate the skin (which water, under normal circumstances, can not do). Thus, although we commonly speak of skin hydration, creams actually "fatten" the skin, a low-polarity environment where water is not welcome!

In short, "polar" is not only a matter of geography or temperature. It may even be useful to explain many phenomena we encounter daily.

November 9, 2014

Draw Me a Terpene

Alexis St-Gelais - Popularization

One of the strangest aspects of the life of a chemist is to constantly be working with something we can (almost) never see as a unit: a molecule. In fact, a considerable part of our job is to draw conclusions from data obtained indirectly in order to deduce the structure of the molecules that we study! Over time, it was therefore necessary to develop ways to represent molecular structures and thus build a collectively accepted and understood image for the compounds we encounter.

A molecule is, by definition, a set of two or more atoms held together by what is called chemical bonds. A bond is in fact a pair of electrons shared between two atoms, which keeps them close to each other. Without going into detail, one basic method of representation is therefore to indicate each of the atoms along with the electrons they share. To be stable, each atom must typically be surrounded by eight electrons, represented by dots, except for hydrogen, which only requires two electrons. Electrons always come in pairs. We call this representation the Lewis model (Figure 1).
Figure 1. Lewis structure of methanol.
This representation, however, is highly cumbersome, and is almost impossible to effectively use for larger molecules. Consequently, chemists have resorted to various simplifications to increase the flexibility of the representation of organic molecules, which often have dozens of atoms. The first simplification is to replace shared electronic pairs by a straight line representing a chemical bond. If several pairs of electrons are shared, the line is doubled or tripled. Pairs of free electrons, such as those of oxygen, are omitted. (Figure 2).
Figure 2. Developed structure of acetone, where electronic pairs are replaced by bonds represented as straight lines.
In organic chemistry, an overwhelming majority of the atoms that we represent are hydrogens and carbons. The simplification therefore continued to avoid having indicating them again and again. The carbons are therefore not shown, and by convention, a juction between chemical bonds, or a blank line tip, is automatically considered to be acarbon. Other atoms, called heteroatoms (other than carbon, C, and hydrogen, H) are still referred to by their chemical symbol (Figure 3).
Figure 3. Developed structure of isopropanol, where carbons have been omitted and are, by convention, situated at the junction of chemical bonds.
Hydrogen, finally, is omitted in molecular representations when it is bonded to a carbon. If we keep in mind that carbon must always have a total of four chemical bonds to be stable, missing bonds are implicitly filled with hydrogen atoms. Carbons showing three visible bonds include one hydrogen, whereas if the carbon has only one visible link, it rather bears 3 hydrogens. Figure 4 shows a complex molecule shown in this simplified manner, which is most commonly used by organic chemists daily.
Figure 4. To the left, the developed structure of  α-terpineol, with all atoms represented. To the right, the same molecule in its condensed form, as commonly used in organic chemistry. Junctions and tips are carbon atoms, and these are conventionnally "filled" with up to 4 links with hydrogens.
In 2013, a team successfully "saw" molecules using a technique of atomic microscopy: a carbon monoxide molecule interacts with the molecule previously deposited on a silver surface, and its oscillation is measured and converted to an image (Figure 5). Note that this is again an indirect representation of the molecule, and not an image obtained by a photographic method: it is rather a translation of the vibrations generated on the carbon monoxide molecule. But as the researchers themselves point out, the similarity between the picture and the molecular schemes is striking. In short, our representations, although simplified, reflect quite well the chemical reality as we currently understand it.
Figure 5. Molecular "pictures" obtained by atomic microscopy. Work of D. G. de Oteyza et al.
With this information, you should decipher more easily the structure of molecules represented in our blogposts and in most organic chemistry texts.

October 31, 2014

The importance of plant identification - Part 3

Hubert Marceau - Popularization

Figure 1: S. lycopersicum (Source)
Have you ever heard of Tomtatoes? It is tomato plant, Solanum lycopersicum (Figure 1), graft on a potato plant, Solanum tuberosum. This gives a plant that bear edible roots (tubers to be more precise) and fruits. Why not them start using all the rest and make a salad with the leaves? Some of you may have already spotted the bad idea in this last sentence, for the other, know that the tomato plant, just like tobacco (Nicotiana tabacum), the pepper (Capsicum annuum), the datura (Datura stramonium), the deadly nighshade (Atropa belladona)... are part of the Solanaceae family and produce toxics alkaloids. Generally, potatoes contains a negligible amount of solanine (and others toxic glycoalkaloids) [Edit: /u/thalassa made me notice that tomato leaves don't containt solanine but tomatine, a non toxic analog.] , but can sometime produce more when they are in bad storage condition. There are known potatoe poisoning case, but they are very uncommon. Basically, you must not eat the tuber when they are green.

This post is not directly related to botanical identification, but I wanted to give you examples of some preconception that we may have on the security of plants. I will be using the toxicity of some of them considered edible. In the case of common foodstuff, the toxic effect often appears after over-consumption, a nutritional imbalance, or a predisposed condition.

Our first case is carambolas, Averrhoa carambola (Figure 2). The star fruit is known to be toxic to people with kidneys troubles since the 80's. Scientist have long though that the toxic compound was oxalic acid. It is only in 2013 that the real culprit was identified: caramboxin. This compound cause hiccups, neurologic and gastric problems, and confusion. People with renal problems are particularly sensitive because the kidney can't filter the product, but there have been reported cases of intoxication in healthy peoples after large consumption of the fruit. In these case, oxalic acid also had a toxic effect since it is dangerous in large quantity.

Figure 2: A. carambola (Source)
Since we are on the subject of oxalic acid, I would like to point out that rhubarb, Rheum rhabarbarum, also contains a lot of this compound.

Let's continue with a case a little bit more known: nutmeg (Myristica fragrans). This spice contains myristicin and elemicin who are both considered to be psychotropic. While it has never been proven, we suppose that the two are turn by the body into MMDA and TMA, two close derivative of MDMA (also know as Ecstasy). Due to their hallucinogenic properties, nutmeg intoxication are usually voluntary but there are known involuntary case. Involuntary case are pretty rare since they require a large quantity: 5 to 10 g, which correspond to a complete nut.

Figure 3: H. alpinum (Source)
Finally, lets talk about Christopher McCandless, the late protagoniste of the movie Into the Wild. Christopher was a young american who, at the age of 24, decided to live the complete summer of 1992 in the Alaska wilderness to live by himself off the land. He was found dead 4 months later. It was believe for a long time that the cause of his death was a confusion between two wild plants that he was using for food: Hedysarum alpinum (edible, figure 3) and Hedysarum boreale spp. mackenziei (toxic, figure 4). However, a more complete analysis of the case tend to demonstrate that he died of lathyrism. The seed of H. alpinum contains oxalyldiaminopropionic acid (ODAP). This amino acid is generally non-toxic, but when consumed in large quantity and the body is stressed, undernourished or starving, it create a degeneration of motors neurons and paralysis. This would have effectively stopped Christopher from being able to forage, eventually starving him to death. The presence of this compound in the seed of H. alpinum was confirmed in 2014. Christopher had no way of knowing the toxicity of the plant.
Figure 3H. boreale (Source)

In most case, the toxic compounds are unknown or only suspected. In others, uncommon interactions cause dangerous effects. Sometimes, a compounds that we think to be the cause of a biological activity is in fact hiding another (we call this internally the "Vakhtang effect"). All these situation demonstrate that the toxicity of plants is often not well understood. For most case the only security that we have is still the same that our ancestors had: if you didn't die when you ate it that mean that I can eat it.

October 24, 2014

The importance of plant identification - Part 2

Hubert Marceau - Popularization

Figure 1: A. ursinum (source)
In 2004, in the canton of Neufchâtel, Switzerland, clients from a restaurant who ordered fish with a bear's garlic sauce, Allium ursinum (Figure 1), went on a painful adventure. Shortly after eating they started to have severe gastrointestinal troubles. After analysis, it was found that the sauce contained colchicine, a toxic alkaloid. This compound is produced by the meadow saffron, Colchicum autumnale (Figure 2), a plant that looks pretty much like bear's garlic and often grows in the same environment. Furthermore, to be edilble, bear's garlic needs to be harvested in the early spring when the first leaves appear and before bolting. As we already saw in the last post, the use of only the leaves for botanical identification can sometimes be tricky. In this particular case the best way to be sure of the identity of the garlic and the saffron, and to a lesser extent the lily-of-the-valley, Convallaria majalis (seen on Figure 3), is to use our nose. Garlic smells like garlic, the others ones don't smell anything. Unfortunately, the smell has a tendency to stick to the finger and interfere with the identification, even more so when we harvest a big batch. This leads to an easy mix-up. This situation is not necessarily common, but can be fatal.

Figure 2: C. automnale (source)
This situation is a good representation of the hazards that can cause a misidentification. As I already have demonstrated, many plants can look the same and be confused with one another. In North America there is also a wild garlic, ramp, Allium tricoccum (Figure 4), that can also be confused with other plants in their juvenile form: Clintonia borealis (edible, young leaves only), Convallaria majalis (toxic), Cypripedium acaule (dubious edibility) and many more.

Figure 3: Comparaison of the leaves (source)
Figure 4: A. tricoccum (source)


Figure 5: H. maximum (source)
Figure 6: H. mantegazzianum (source)
Another interesting case, albeit less common, is the Cow Parsnip, Heracleum maximum (Figure 5). America's First Nations ate the stems of this plant like a legume, and today it is still considered edible (its consumption is marginal though). This is an interesting case due to its great ressemblance to its cousin: the Giant Hogweed, Heracleum mantegazzianum (Figure 6). The later has the disagreable properties of causing serious burns when we enter in contact with any part of the plant. If you enter in contact with the plant, hide the affected part from the sun or any strong light during at least 1 to 2 months. By experience, even with this precaution, it is possible that the affected skin turn a bit darker, but, at least, it won't cause blisters. A misidentification can therefore have serious consequences. It is important to note that Cow Parsnip can have the same effect on sensitive people, but the latter is generally considered safe if peeled. Sensitive people can also have the same problems when touching limes or other plants: it is called phytophotodermatitis.

Finally, here is a very special case. To keep with the tradition of the last post, I will ask you to check the two following pictures and to keep an eye out for what could differentiate those two plants.
Figure 7: Plant A

Figure 8: Plant B
It is two varieties of the same plant, Acorus calamus (A, source) and Acorus calamus var. americanus (B, source). The difference between these two plants are the number of chromosomes, and their concentration in β-asarone, a carcinogenic compound that also cause vomiting. The American variety is diploid (2n) and contains no or almost no β-asarone. The European and Asian version are tri- or tetraploid (3n and 4n) and contain a lot of β-asarone. I will give you more information on these kind of chemical and environmental variation in a later post.

There is still a lot of plant that can be confused, which we will see later. In the next post, we will explore the toxicity of edible plants (!).

Edit: My thanks to /u/Thallassa on reddit for the revision and input.

October 20, 2014

The importance of plant identification - Part 1

Hubert Marceau - Popularization

Figure 1C. sativa (source)
October 1st 2014 will surely be a memorable day for a retired man from Georgia, USA. To his suprise, a heavily armed police force assisted by a K9 unit and a helicopter dropped in his garden. The local police department were suspecting the presence of Cannabis sp. (Figure 1), also known as marijuana. To their surprise they only found Abelmoschus esculentus (Figure 2), or okra, a comestible fruit.

Figure 2 : A. esculentus (source)



Plant identification is a crucial process in the field of naturals products. In the case presented here, it is hard to confuse the two plants when we look at them closely. But in some case even a close inspection may not be enough for an untrained eyes. Would you be able to easily tell the difference between cannabis and kenaf, Hibiscus cannabinus (Figure 3)? Better, would you be able to describe the difference? Sometimes it is not an easy task.

Figure 3 : H. cannabinus (source)

Here is another example of similar plants that can be sometime hard to distinguish for an untrained eyes: Kalmia polifolia, Kalmia angustifolia and Rhododendron groenlandicum. The first two are toxics plants that contains grayanotxins; the last one is used to make tea. In this case, an error could be dangerous. The figure 4 show the leaves (which are often a very important identification criterion) of each of these plants and others from the same family which are often confused.

You can see that the difference can sometimes be subtles (from left to right: Rhododendron groenlandicum, Kalmia angustifolia, Kalmia polifolia, Chamaedaphne calyculata and Andromeda polifolia). It is very important to specify that an good identification must be based on many morphological characteristics and be done on a complete plant, ideally with a fruit or a flower available.

Figure 4 : Multiple Ericaceae leaves (source, used with author permission)

In this last example, I would like to bring your attention to the characteristics of hair or a fold on the side being present, or not, and the general shape of the leaves. Even by looking at the parameters, some leaves are still hard to differentiate. In these cases we couldn't tell with certainty without having the complete plant.

Lastly, I would like to show you the two following plants pictures. Pay particular attention to the leaves: the shape, the stems, the color, how they attach on the branch, etc. What do you see?

Figure 5: Plant A

Figure 6: Plant B

These two pictures are in fact of the same species! Eucalyptus globulus (source figure 5 and source figure 6). This kind of dimorphism is called heteroblasty. It is a variation in the shape of the leaves and the plant in general in function of the age. The first image is a young specimen and the second is a mature one. This situation seems to be specially common in New-Zealand. Sometimes the dimorphism is strong enough to confuse even professional botanist. Closer to us (in North America), young balsam poplars have leaves that are much larger than their mature counterpart.

Plant identification is a very important aspect that can't be taken lightly in the field of natural products. Next time we will see examples where a misidentification can bring potentially serious consequences.

Edit: My thank to /u/Thallassa on reddit for the correction.

September 29, 2014

Introducing plants from the boreal forest of Quebec - Card # 3 : Coptis trifolia (L.)



Laurie Caron - Plant card

Figure 1 : Plant representation.

Latin name: Coptis trifolia (L.) and its former name is Coptis groenlandica (Oeder) Fern.


Common Names: Goldthread Greenland, Sabouillane, Sibouillane, Gold-thread. 


Small herbaceous perennial with rhizomes slender, wiry and yellow gold (Figure 1). The leaves of this plant are basal, long-stalked, glossy superiorly (Figure 2)1. The Coptis trifolia is very common in the undergrowth of the boreal forest and widely known for its biological properties. Most studies deal with the active compounds in the rhizome of this plant is recognized several alkaloids (berberine, palmatine, jatrorrhizine, coptisine, columbamine and epiberberine)2 for their many properties. Berberine is the molecule which is found in greater quantities in dry rhizomes C. trifolia (5.20 to 7.69 % w / w)3.

 Berberine is known to treat various intestinal infections, to be antibacterial, antiviral and anti-inflammatory3. Recent studies also show that berberine possesses anti-tumor properties and relatively high cytotoxicity4 and would be a good candidate as a general antineoplastic agent (anticancer agent)3.



Figure 2 : Representation of leaves of C. trifolia




On the other hand, the use of various forms rhizomes (infusion, decoction, etc.) is listed in the literature widely ethnobotanical uses of Native American tribute Iroquois5, Micmac6 and Algonquian7. The biological activities attributed to these concoctions are relieving digestive disorders, treatment of respiratory problems and heart, relief of fever and toothache5–7.

Fresh Bitter roots were chewed and it could also help heal sores inside the mouth often caused by tobacco use. 

The yellow rhizome also used for dyeing skins of native americans (indians)1.
















 Bibliography

(1)       Marie-Victorin. Flore Laurentienne; 3e ed.; Gaëtan Morin éditeur: Montréal, 2002.
(2)         He, Y.; Hou, P.; Fan, G.; Arain, S.; Peng, C. Comprehensive Analyses of Molecular Phylogeny and Main Alkaloids for Coptis (Ranunculaceae) Species Identification. Biochemical Systematics and Ecology 2014, 56, 88–94.
(3)         Tang, J.; Feng, Y.; Tsao, S.; Wang, N.; Curtain, R.; Wang, Y. Berberine and Coptidis Rhizoma as Novel Antineoplastic Agents: a Review of Traditional Use and Biomedical Investigations. Journal of ethnopharmacology 2009, 126, 5–17.
(4)         Lin, L.-T.; Liu, L.-T.; Chiang, L.-C.; Lin, C.-C. In Vitro Anti-hepatoma Activity of Fifteen Natural Medicines from Canada. Phytotherapy research : PTR 2002, 16, 440–444.
(5)         Herrick, J. W. Iroquois Medical Botany, State University of New York, Albany, 1977, p. 322.
(6)         Speck, F. G. and R. W. D. Utilization of Animals and Plants by the Micmac Indians of New Brunswick. Journal of the Washington Academy of Sciences 1951, 250–259.
(7)         Black, M. J. Algonquin Ethnobotany: An Interpretation of Aboriginal Adaptation in South Western Quebec; Canada, N. M. of, Ed.; 65th ed.; Ottawa, 1980; p. 167.

September 22, 2014

Introducing plants from the boreal forest of Quebec - Card # 2 : Anaphalis margaritacea (L.) Benth. & Hook


Laurie Caron - Plant Card

Latin name: Anaphalis margaritacea (L.) Benth. & Hook
Common names: Immortal, Immortal silver, Life-everlasting, Anaphale daisy. 

Anaphalis margaritacea is a herbaceous, perennial and widespread in the temperate boreal zone1. It is often found in fields and roadsides (Figure 1). You can easily recognize this plant by its long stem (30-100 cm) and the woolly inferiorly and superiorly pubescent leaves (Figure 2). These flowers are made ​​highbush and white bracts finely striated (Figure 3)1. The chemical compounds in different parts of the immortal are still poorly studied. Some articles mention that this plant was used in traditional medicine to treat colds, coughs, rheumatism and respiratory problems2.

The advantages of this plant are listed for various types of compounds are flavonoids, triterpenes and diterpenes and also hydoxylactones2. These compounds are known for their antioxidant2, anti-tumor, anti-inflammatory and antiviral activities3.

Figure 1 : Representation of the plant

Figure 2 : Leaves of the plant seen from below






 More specifically, the aqueous ethanolic extract of the plant leaves was identified as having interesting antibacterial activity against Staphylococcus aureus (S. aureus) with 18 mm of inhibition (disk diffusion method) area4. The extract of the aerial parts have also demonstrated significant antibacterial activity against B. cereus, P. aeruginosa and E. coli4. The few studies on the antibacterial activity of Anaphalis margaritacea all agree to say that this plant would have an interesting potential for use as an antibacterial agent in various pharmacological and medical sectors5.

Figure 3 : Representation of flowers of Anaphalis margaritacea (L.)


Bibliography

(1)      Marie-Victorin. Flore Laurentienne; 3e ed.; Gaëtan Morin éditor: Montréal, 2002.
(2)      Ren, Z.; Wu, Q.; Shi, Y. Flavonoids and Triterpenoids from Anaphalis Margaritacea. Chemistry of Natural Compounds 2009, 45, 610–611.
(3)     Ren, Z.-Y.; Zhang, Y.; Shi, Y.-P. Simultaneous Determination of Nine Flavonoids in Anaphalis Margaritacea by Capillary Zone Electrophoresis. Talanta 2009, 78, 959–963.
(4)      Borchardt, J. R.; Wyse, D. L.; Sheaffer, C. C.; Kauppi, K. L.; Fulcher, R. G.; Ehlke, N. J.; Biesboer, D. D.; Bey, R. F. Antimicrobial Activity of Native and Naturalized Plants of Minnesota and Wisconsin. 2008, 2, 98–110.
(5)    Haider M. Hassan, Zi-Hua Jiang, Christina Asmussen, Emma McDonald, W. Q. Antibacterial Activity of Northern Ontario Medicinal Plant Extracts. Canadian Journal of Plant Science 2014, 94, 417–424.