Mass Spectroscopy and Organic Molecules

What happens when an organic chemist makes a new molecule?
How do they know what the structure of the new molecule is?
They use lots of different techniques to determine the molecular mass and structure of the new molecule, one of which is mass spectroscopy.
Mass spectroscopy tells you the molecular mass of the molecule, and, it gives a good indication of how the atoms making up the molecule are put together. And it does this by breaking the molecule up!
Find out more about how mass spectroscopy can be used to determine the structure of organic molecules in our tutorial
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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.

Chiral Centres and Chiral Molecules

What is a chiral molecule?
How do you find the chiral centre, or chiral carbon, in an organic molecule?
What makes a molecule chiral?
Why is chirality important?

These are all excellent questions, and AUS-e-TUTE has just uploaded some excellent resources to help you answer these questions and apply the concepts.

AUS-e-TUTE Members should log-in to use the new resources (tutorial, game and test with worked solutions).
If you are not an AUS-e-TUTE there is a "free-to-view" tutorial currently available for evaluation purposes at http://www.ausetute.com.au/chirality.html

The Smell of Freshness

Organic compounds are added to cleaning products and air fresheners to make the air smell fresh and clean. Scientists are taking a closer look at the chemistry behind the use of these compounds to determine whether they are hazardous to human health.

One of the organic compounds that is widely used to provide the "smell of freshness" is a molecule known as limonene (1-methyl-4-(1-methylethenyl)-cyclohexene). The 2-dimensional structural formula of limonene is shown on the right.

Limonene is a colourless liquid at room temperature and pressure and is found naturally in the rind of citrus fruits such as lemons. It is one of the compounds that contributes to the typical odour of citrus fruit.
Commercial quantities of limonene are produced from citrus fruits using centrifugal separation or steam distillation.

Scientists are studying the reactions of limonene closely because the chemical reactions of this molecule with the ozone in the air in your home are the same as the chemical reactions that occur in the atmosphere that produce secondary organic aerosols (SOAs), microscopic particles suspended in the air, which contribute to the visible haze known as smog in densely populated areas.

The researchers tested various different scenarios for the production of SOAs in the home from limonene and found that the concentration of SOAs produced was between 5μg/cm³ and 100μg/cm³. The acceptable level of aerosols in breathable air is about 12μg/cm³.

The researchers suggest that the best way to reduce SOAs in your home is to either use unscented cleaners or to keep windows open while cleaning. 

Reference:
Somayeh Youssefi, Michael S. Waring. Transient Secondary Organic Aerosol Formation from Limonene Ozonolysis in Indoor Environments: Impacts of Air Exchange Rates and Initial Concentration Ratios. Environmental Science & Technology, 2014; 48 (14): 7899 DOI: 10.1021/es5009906

Further Reading:
Empirical Formula
Molecular Formula
2-Dimensional Structural Formula
Condensed Structural Formula
Skeletal Structural Formula
Percentage Composition
Parts Per Million (ppm) Concentration
Molar Mass

Suggested Study Questions:

1. Write the molecular formula for limonene.
2. Give the empirical formula for limonene.
3. Calculate the percentage of
   • carbon in a molecule of limonene
   • hydrogen in limonene
4. Draw a skeletal structural formula for limonene.
5. Limonene has the IUPAC name 1-methyl-4-(1-methylethenyl)-cyclohexene. Draw the 2-dimensional structural formula for limonene and circle each of the following groups:
   • cyclohexene parent hydrocarbon in red
   • methylethenyl branch in blue
   • methyl branch in black
6. Would you classify limonene as a saturated or unsaturated hydrocarbon? Explain your answer.
7. Convert these concentrations in μg/cm³ to concentrations in parts per million (ppm)
• 5μg/cm³
• 12μg/cm³
• 100μg/cm³
8. Calculate the molar mass of limonene.
9. Calculate the mass of limonene in 100 L of air at 25^oC and 100 kPa for each of the following concentrations:
   • 5μg/cm³
   • 12μg/cm³
   • 100μg/cm³

Molecule with Anti-Cancer Kick

In 2013, medical researchers found a molecule that fights cancer in animals by boosting the cell's production of a powerful natural antitumor protein known as TRAIL. The Researchers referred to this anti-cancer molecule as TIC10, short for TRAIL Inducing Compound number 10.
The structure of this molecule, as confirmed by mass spectroscopy, was published at this time as is shown below:

Chemists at The Scripps Research Institute (TSRI) found a way to synthesize this molecule in the laboratory. However, when the Chemists gave their molecule to Biologists to test on cancer cells, this molecule failed to show any anti-cancer activity!
So, the Chemists asked the Biologists to supply some of the TIC10 that had shown anti-cancer activity. The Chemists spent months analyzing both TIC10 molecules to determine their exact molecular structure. And they discovered that the molecule the biologists had shown to fight cancer did not have the structure that was originally published, so the molecule that the Chemists had synthesized in their laboratory would not fight cancer cells,.
However, the Chemists found that the molecule that DOES fight cancer cells has a very similar structure. The structure of the active molecule is shown below:

Note that the structure originally published for TIC10 had the three nitrogen containing rings in a straight line. This new, correct, structure for TIC10 has two of the nitrogen containing rings in a straight line, but the third ring sticks out at an angle from the other two. Only this "angular" isomer (the molecule with a kick) shows any anti-cancer activity.

Kim D. Janda, the Ely R. Callaway Jr. Professor of Chemistry and member of the Skaggs Institute for Chemical Biology at TSRI has been quoted as saying, "One lesson from this has got to be: don't leave your chemists behind".
(http://www.sciencedaily.com/releases/2014/05/140519184505.htm)

Reference:
Nicholas T. Jacob, Jonathan W. Lockner, Vladimir V. Kravchenko, Kim D. Janda. Pharmacophore Reassignment for Induction of the Immunosurveillance Cytokine TRAIL. Angewandte Chemie, 2014; DOI: 10.1002/ange.201402133

Further Reading
Molecular Formula  
Condensed Structural Formula 
2-Dimensional Structural Formula
Skeletal Formula
Percent Composition
Functional Groups
Benzene
Mass Spectroscopy for Structural Determination

Suggested Study Questions:

1. Refer to the structure of TIC10 as shown above. In one molecule, how many
   • carbon atoms are present?
   • hydrogen atoms are present?
   • oxygen atoms are present?
   • nitrogen atoms are present?
2.  Write the molecular formula for a molecule of TIC10.
3. For the TIC10 molecule, calculate the percent by mass of
   • carbon
   • hydrogen
   • oxygen
   • nitrogen
4. Convert the skeletal structure for the active anti-cancer molecule into a 2-dimensional structural formula.
5. Circle one benzene ring in the structure of the active anti-cancer molecule.
6. Circle and name the functional group containing an oxygen atom on the active anti-cancer molecule.
7. What value do you expect for the mass-to-charge (M/Z) peak on a mass spectrum of the anti-cancer TIC10 compound ?
8. Do you think mass spectroscopy alone could be used to distinguish between the two structures proposed for TIC10 above? Explain your answer.

Chemical Formula

What's the difference between a molecular formula, structural formula, condensed structural formula and semi-structural formula?
I'm glad you asked :)
AUS-e-TUTE has uploaded new resources on all these topics!
AUS-e-TUTE Members should log-in to the Test Centre to use the new tutorials, games, tests etc
(The syllabus guides for all Australian States/Territories: QLD, NSW, ACT, VIC, TAS, SA and WA have been updated to include these new resources, and the USA's SAT and AP syllabus guides have also been updated).

Not an AUS-e-TUTE Member?
There are free versions of the new tutorials available to you.
Follow the links from
http://www.ausetute.com.au

Skeletal Formula

Resources on the "bare bones" of structural formula, known as skeletal formula, have just been added to AUS-e-TUTE.

Members should log-in to use the new tutorial, game and test.

Not a member?
A free tutorial is available: http://ausetute.com.au/skeletal.html

Structure of Benzene

AUS-e-TUTE has just uploaded new resources for the Benzene topic.
You will find the new Structure of Benzene tutorial, game and test under the Aromatic Compound heading when you log-in to the Test Centre.
Relevant syllabus study guides have also been updated to include these new links.
The key concepts can be found in the "free-to-view" tutorial at
http://www.ausetute.com.au/benzene.html
There is a clickable link on that benzene page which will take AUS-e-TUTE members straight to the complete new tutorial.