Omega-3 Acids Fight Cancer

Scientists at the University of Guelph have found that omega-3s from fish are better at preventing cancer than omega-3s from plants.

"Omega-3s" refer to omega-3 fatty acids which are a type of long-chain, polyunsaturated carboxylic  acid. Long-chain carboxylic acids are referred to as "fatty acids".
The three omega-3 fatty acids studied were: 

• α-linolenic acid (ALA) which is found in plant seeds and oils

• eicosapentaenoic acid (EPA) which is found in fish, algae and phytoplankton

• docosahexaenoic acid (DHA) which is found in fish, algae and phytoplankton

 The skeletal structural formula for α-linolenic acid is shown below:

 The IUPAC name of α-linolenic acid is (9Z,12Z,15Z)-9,12,15-octadecatrienoic acid. 
The carbon atom of the carboxyl functional group (COOH) is labelled as 1, the next carbon atom in the chain is 2, then 3, etc, up until we reach the last carbon in the chain, carbon 18. The parent hydrocarbon for this molecule is therefore octadecane, with a suffix added for the carboxyl functional group, so we have octadecanoic acid. 
Along the way we find 3 (tri) double bonds (en) at carbons numbered 9, 12 and 15, so we modify the name of the carboxylic acid in one of two ways:

• 9,12,15-octadecatrienoic acid

• octadeca-9,12,15-trienoic acid

The "Z" indicates the 3-dimensional geometry,  in this case the "Z" geometry equates to a "cis" geometry.
So why would  (9Z,12Z,15Z)-9,12,15-octadecatrienoic acid be called an omega-3 acid?
There is an alternative naming "system" (not IUPAC)  in which the first carbon atom is not labelled 1, but instead it is called "alpha" (α), and, the carbon atom at the end of the long hydrocarbon chain is called "omega" (ω). Then, the last carbon atom in the chain (omega) is labelled 1, and you start counting back towards the carboxyl functional group. If you do this, you will find that carbon 3 has a double on it, hence, (9Z,12Z,15Z)-9,12,15-octadecatrienoic acid is called an omega-3 fatty acid. The 3 indicates the position of the first double bond from the omega carbon atom.

The skeletal structural formula of eicosapentaenoic acid is shown below:

The IUPAC name for this molecule is (5Z,8Z,11Z,14Z,17Z)-5,8,11,14,17-Icosapentaenoic acid. 
There are 20 carbon atoms in the chain so the parent hydrocarbon chain is icosane, which is modified with a suffix because there is a carboxyl functional group, icosanoic acid.
There are 5 (pent) double bonds (en) located on carbons 5, 8, 11, 14 and 17, so the name of this molecule is either:

• 5,8,11,14,17-icosapentenoic acid

• icosa-5,8,11,14,17-pentenoic acid

Once again, the Zs in the name refer to the geometry (same as a "cis" geometry in this case).
Notice that, in the alternative naming "system" in which the last carbon atom in the chain is labelled "omega" and then you count backwards from this, we see that the first double bond encountered is on carbon 3, so this molecule is also referred to as an omega-3 fatty acid.

The skeletal structural formula below is that of docosahexaenoic acid:

This molecule has the IUPAC name (4Z,7Z,10Z,13Z,16Z,19Z)-4,7,10,13,16,19-Docosahexaenoic acid. 22 carbon atoms in the chain (docosa), 6 (hexa) double bonds on carbons 4, 7, 10, 13, 16, 19 and a carboxyl functional group: 4,7,10,13,16,19-docosahexaenoic acid or docosa-4,7,10,13,16,19-hexenoic acid. Zs indicate geometry (same as "cis" in this case).
Using the alternative numbering system, the first double bond occurs of the third carbon atom from the omega carbon atom (last carbon in the chain) so it is also classified as an omega-3 fatty acid.

While all three of these omega-3 fatty acids were shown to be effective in reducing the size of tumours in mice, however, higher doses of the plant-based α-linolenic acid was required to deliver the same impact as the omega-3 fatty acids found in fish (icosapentaenoic acid and docosahexaenoic acid)



Reference:

Jiajie Liu, Salma A. Abdelmagid, Christopher J. Pinelli, Jennifer M. Monk, Danyelle M. Liddle, Lyn M. Hillyer, Barbora Hucik, Anjali Silva, Sanjeena Subedi, Geoffrey A. Wood, Lindsay E. Robinson, William J. Muller, David W.L. Ma. Marine fish oil is more potent than plant based n-3 polyunsaturated fatty acids in the prevention of mammary tumours. The Journal of Nutritional Biochemistry, 2017; DOI: 10.1016/j.jnutbio.2017.12.011

Further Reading:
Introduction to naming organic molecules: http://www.ausetute.com.au/namctut1.html
Introduction to functional groups: http://www.ausetute.com.au/fungroup.html
Fatty acids: http://www.ausetute.com.au/fattyacid.html 
Structure and properties of carboxylic acids: http://www.ausetute.com.au/carboxyl.html
Molecular formula: http://www.ausetute.com.au/molecularformula.html
2-Dimensional structural formula: http://www.ausetute.com.au/structural2D.html
Condensed structural formula: http://www.ausetute.com.au/condensedsf.html
Skeletal structural formula: http://www.ausetute.com.au/skeletal.html
Cis-trans isomers: http://www.ausetute.com.au/cistranso.html 


Suggested Study Questions:

1. What functional group is common to all fatty acids? 
2. Define the following terms as they are used in chemistry:
   • saturated
   • unsaturated
   • monounsaturated
   • polyunsaturated
3.  Give the molecular formula for each of the three omega-3 acids in the article
4. The structural formula given in the article are referred to as "skeletal". What does this mean in chemistry?
5. Draw a 2-dimensional (full display) structural formula for each of the omega-3 acids in the article.
6. On the structural formula of each of the three omega-3 acids circle the:
   
   • carboxyl functional group in red
   • double bonds in blue
7. What features are common to three omega-3 acids in the article?
8.  In what ways do the the three omega-3 acids in the article differ?
9. You have probable heard about omega-6 acids. How do you think an omega-6 acid will be similar to an omega-3 acid?
10. How will an omega-6 acid be different from an omega-3 acid?
11. What is meant by a cis isomer and a trans isomer?
12. All the omega-3 fatty acids in the article are the cis isomers. Build a model, and draw, a trans isomer of one of the fatty acids.

Bee Killing Chemicals?

This morning I read a story in the Sydney Morning Herald, "Bunnings to pull pesticide allegedly linked to bee deaths".  According to the story, cans of Yates "Confidor" which have been stocked by the homewares and hardware giant Bunnings, contains neonicotinoid, a class of compounds used as an insecticide that some studies have suggested affects bee's navigation and immune systems and ultimately leads to the death of the bee colony. Indeed, a story on this appeared in New Scientist in July 2017 in which Dave Goulson at the University of Sussex, UK, is quoted as saying, "Although the field trial results varied between countries, the overall evidence points to harmful effects for bees. I think you’d have to be pretty unreasonable at this point not to accept that, at least some of the time, these chemicals harm bees when used in normal farming practice.”  The same story quoted Richard Schmuck of Bayer, one of the makers of this class of insecticides, as saying, "We remain confident that neonicotinoids are safe when used and applied responsibly."

As the name neonicotinoids suggests, these are "new" molecules based on the molecular structure of nicotine shown below:

 Nicotine has been used as a pesticide for over 200 years. It is found lots of plants.  Up to 3% of the mass of the tobacco plant is nicotine, and trace amounts of nicotine are found in vegetables like eggplants, potatoes and tomatoes. When used as a pesticide,  it degrades rapidly in the environment and is not very selective so it is not really a good pesticide. For instance, a dose of 1mg per kg of body mas can kill a human.
Development of neonicotinoids began in the 1980s by Shell and1990s by Bayer. Neonicotinoids are generally less toxic to birds and mammals than they are to insects, and, some of the breakdown products are also toxic to insects, this is why they can be used as insecticides.
Consider the structural formula of imidacloprid, an example of a neonicotinoid and one of the most widely used insecticides:

 Imidacloprid was patented by Bayer in 1985 as the first commercial neonicotinoid. Traditionally insecticides were coated onto plants, "crop dusting", but neonicotinoids like  imidacloprid are water soluble and break down slowly in the environment so they are absorbed by plants. Bees are exposed to these compounds in the plant's pollen.
The early 2000s saw the introduction of two other neonicotinoid compounds;  clothianidin and thiamethoxam. 

clothianidin	thiamethoxam

Clothianidin can be used as a spray, dust or injectable liquid, depending on which plants it is being to protect.
In 2013 the European Union restricted the use of imidacloprid, clothianidin and thiamethoxam on crops that attract bees.

References:
http://www.smh.com.au/national/bunnings-to-pull-pesticide-allegedly-linked-to-bee-deaths-20180113-h0htzq.html
https://www.newscientist.com/article/2139197-strongest-evidence-yet-that-neonicotinoids-are-killing-bees/

Suggested Further Reading
IUPAC Nomenclature:  http://www.ausetute.com.au/namctut1.html
Introduction to Functional Groups: http://www.ausetute.com.au/fungroup.html
Molecular Formula: http://www.ausetute.com.au/molecularformula.html
2-Dimensional Structural Formula: http://www.ausetute.com.au/structural2D.html
Skeletal Structural Formula: http://www.ausetute.com.au/skeletal.html
 Introduction to Polarity of Molecules: http://www.ausetute.com.au/molpolar.html
Intermolecular Forces and Solubility:  http://www.ausetute.com.au/intermof.html
Aqueous Solutions (water as a solvent): http://www.ausetute.com.au/aqueous.html

Suggested Study Questions:

1. Use molecular model kits to build models of  the following molecules:
   • nicotine
   • imidacloprid
   • clothianidin
   • thiamethoxam
2. Draw a 2-dimensional (full display) structural formula for each of the following molecules:
   • nicotine
   • imidacloprid
   • clothianidin
   • thiamethoxam
3. Write the molecular formula for each of the following molecules:
   • nicotine
   • imidacloprid
   • clothianidin
   • thiamethoxam
4. Consider the nicotine molecule. Do you expect it to be soluble in water? Explain your answer.
5. Consider a molecule of imidacloprid. Do you expect it to be soluble in water? Explain your answer.
6. What property of clothianidin enables it to be used as a spray? Explain this property in chemical terms.
7.  What alteration to the structure of a nicotine molecule could you make so that it would become more soluble in water?
8. Carefully compare the structure of clothianidin and thiamethoxam (the molecular models you built could be useful here). In what ways are the molecules:
   • similar
   • different
9. Considering only the structure of nicotine and the neonicotinoids in this article, explain why nicotine might be more toxic to humans than the neonicotinoids.
10. Compare the quotes from Dave Goulson and Richard Schmuck in the article. In what ways are the two quotes:
    • similar
    • different
11. Imagine you have been asked by your government to decide whether or not to ban the use of neonicotinoids in agriculture. What would you advise? Explain why.