Determination of structures of small molecules: NMR spectroscopy

The third and final segment of small molecular structure determination is nuclear magnetic resonance (NMR) spectroscopy, as is one of the strongest tools that chemists have in their arsenal. Like infrared (IR) spectroscopy, it involves illuminating molecules with light of the radiofrequency.

Nuclear magnetic resonance spectroscopy is based on the same technology as MRI, magnetic resonance imaging, that is used for medical and research. MRI will be the focus of another article.

What is spectroscopy?
Molecules can absorb or emit light. How they absorb and emit light can tell us about the molecule itself. The science that involves shining light onto a molecule is called spectroscopy. Studying how molecules emit light is also called spectroscopy.

What is NMR spectroscopy?
Nuclei have their own magnetic field, so when they are placed in an external magnetic field (inside an electromagnet), they will line up with and against the field.

Shining electromagnetic radiation (radiofrequency) onto the molecules can change the numbers aligned with and against the external magnetic field.

What does NMR spectroscopy tell us?
The types and amount of radiofrequency radiation absorbed can tell us several things.

• What atoms are present- carbon, hydrogen, titanium and many others
• How many of each atom is present
• Whether the molecule is symmetric (for example: aniline is symmetric)

• Which atoms are connected to with atoms. Chemists have advanced NMR techniques such as COSY (pronounced like nice and cosy), TOCSY (pronounced toxy) and ROESY (pronounced rosy).
• Which atoms are close in space to other atoms. Chemists have special NMR techniques such as NOESY (pronounced nosy) 

This concludes these series of articles on small molecule structure determination. Hopefully, it was entertaining and gives a glimpse of the world of chemistry. 

I would like to apologize for giving a very abridged stories of mass spectroscopy, NMR spectroscopy and IR spectroscopy. I intentionally wrote this for people with very little chemistry knowledge.

Determination of structures of small molecules: IR spectroscopy

The second segment of small molecular structure determination is IR spectroscopy. IR spectroscopy stands for infrared spectroscopy. IR spectroscopy tells us specific characteristics that the molecule has, which helps to narrow down possibilities.

It's like CSI and other detective dramas. Consider a group of people, one of which is the culprit. If I know that the culprit has black hair, I can narrow down the potential suspects. 

What is spectroscopy?
Molecules can absorb or emit light. How they absorb and emit light can tell us about the molecule itself. The science that involves shining light onto a molecule is called spectroscopy. Studying how molecules emit light is also called spectroscopy.

What is IR spectroscopy?
Infrared spectroscopy is where infrared light is shone onto a molecule and seeing what it absorbs. Consider aniline, which was introduced in mass spectrometry.

Aniline has a nitrogen connected to a hydrogen (an N attached to a H).

This causes the molecule to absorb specific types (wavelengths) of IR light. This shows up in the IR spectrum of aniline is shown below and the N-H dip is seen, where IR light is absorbed by aniline.

So if a scientist finds a molecule that he thinks is aniline. It has a mass of 93 Daltons, which is shown by mass spectrometry. It also has N-H which is shown by IR spectroscopy. This helps confirm to the scientist that they are correct.

If infrared spectroscopy is still not enough to work out what molecule the molecule is, we can the ultimate weapon: NMR spectroscopy.

Determination of structures of small molecules: Mass spectrometry

The first segment of small molecular structure determination is mass spectrometry. Simply speaking, if you want to deduce what a molecule is, one way of doing this is to measure the mass of it.

Let's say someone identifies an unknown animal. You weigh it and it weighs 7000 kg. You know elephants weigh 7000 kg. The unknown animal may possibly be an elephant!  (Stupid analogy, but it's the idea that counts)

The first problem in this method is that molecules are very small. For example, if the mass of an atom was mass of a elephant. The mass of an actual elephant would be larger than the mass of the moon. Because we are dealing with such small masses, we use a different unit of mass when we are talking about molecules. The unit we use is called the Dalton or Da.

1 Da= 1.66 x 10 ^-27 kg

How do we measure such small masses? With a miraculous machine called the mass spectrometer.

The mass spectrometer
The original mass spectrometer was very simple. Take a compound and heat it up so it vaporises into a gas. With the molecules now in the gas phase, fire high speed electrons at them to knock out an electron from them. This leaves a positively charge ion (a cation of the molecule).

This cation can be accelerated using its charge (passed through a potential difference). The positively charge molecule is then pass through a magnetic field which deflects charged molecules.

The charged molecules hit a detector. How much the molecule has deflected is based on its mass. Lighter molecules (the blue line) get deflected more than heavier molecules (the red line). A chemist can judge the mass of a molecule based on where it hits the detector.

Mass spectrometry in action

Suppose a chemist synthesized a molecule called aniline. Aniline is a very important compound that is used to make many chemicals including pharmaceuticals.

To check whether it is indeed aniline that was synthesized, he runs it in a mass spectrometer and this is what the machine gives out.

Now, the chemist knows he has aniline and can continue his research to save the world.

What happens if two things have the same mass?

One could easily envisage a problem with the above scenario. What if the chemist didn't know what molecule he had? The mass spectrometer tells you that a molecule has a mass of 93 Daltons, but many molecules have that mass. 

It's like asking, "I know the person I am interested is 93 kg, which individual in the world is it?" There are many people in the world that weigh 93 kg, so mass spectrometry alone doesn't always provide the answer. This is where IR spectroscopy and NMR spectroscopy come to the rescue. 

Basics of small molecular structure determination

This is going to be a multiple series post on the structure determination of small molecules. When a chemist synthesizes what he/she thinks is an exciting new compound, how do they know that they in fact succeeded? When a chemist thinks he has isolated an exotic compound from a natural product, how is it that the structure of this molecule is determined?

This brings us into the domain of structure determination. This article will be split up into 3 components, each outlining a different technique used in structure determination

• Mass spectrometry
• IR spectroscopy
• NMR spectroscopy

Hopefully, these sets of articles will give insight into how chemists carry out their routine. :)