Most scientific research is directed towards answering a question. Fortunately for researchers, there are a lot of questions in science that don’t yet have answers, some of which are quite fundamental. If you do a quick google search for ‘unanswered questions in science’, for example, you’ll come across questions like:
- What is spacetime?
- What is dark matter?
- What happened before the big bang?
- How big is the universe? And what shape is it?
These (and similar) questions receive quite a bit of media attention, probably because the general public find them just as interesting as scientists do! With this in mind, I thought it might be interesting to write something about a ‘fundamental’ question that has troubled scientists for years. It’s not a question from physics, like the ones listed above and many other ‘fundamental’ questions, but instead one that is rooted in chemistry. The question is this:
- What is the origin of homochirality in biological systems?
If you’ve never come across the word ‘homochirality’, this question probably makes no sense to you at this point, but hopefully when you’ve finished reading this post you’ll agree that this question is both ‘fundamental’ and very interesting. Let’s start by finding out what ‘chirality’ is and what ‘homochirality’ means.
Chirality and homochirality
The term ‘chirality’ is used in many areas of science. Here we’ll focus on chemistry, where it is most often used in relation to molecules. A chiral molecule is one that is non-superimposable on its mirror image. To understand what this means, place both of your hands flat on the table in front of you. You’ll notice three things:
- You have your hands on the table (sorry, couldn’t resist)
- Your left hand is the mirror image of your right hand and vice versa (assuming you have 5 digits on both hands, and we ignore fine detail)
- No matter what you do, you cannot superimpose your left hand onto your right hand. You can align your thumbs and fingers, but only by flipping one of the hands over so that they are palm-to palm or back-to-back
You can lift your hands up now…
The non-superimposability of your hands is the reason why left and right-handed scissors exist. It’s also the reason why you can’t shake somebody’s right hand using your left hand.
The concept of ‘handedness’ is quite handy (sorry) in chemisty. Certain molecules can exhibit handedness; one example is CHFClBr, shown below.
In this molecule, four different atoms (H, F, Cl and Br) are bonded to a central carbon atom in a tetrahedral geometry. It may not be obvious at first, but there are two distinct ways in which we can arrange the four peripheral atoms around the central carbon atom, as shown below.
The arrangement on the left is the same as in the first diagram. The one on the right is its mirror image. No matter how we rotate and move the structure shown on the left, we can never superimpose it onto the one shown on the right.
Any other way that you arrange the coloured spheres, for example with the green one on top, can be rotated to form one of the two shown above. That means not only are there two distinct ways to arrange the atoms, but there are only two.
You can think of one of the two forms shown above as being ‘left-handed’ and one as being ‘right-handed’, although it’s not obvious which is which, as we haven’t introduced any convention to allow you to label them as such.
So, CHFClBr is a chiral molecule; it is non-superimposable on its mirror image. It is possible to have a bottle of this material containing:
- Only molecules in the left-handed form, or
- Only molecules in the right-handed form, or
- A mixture of the two forms, in any proportion
The two forms are called ‘enantiomers’; they have the same chemical and physical properties but, curiously, interact with polarised light differently. For this reason, you’ll sometimes see enantiomers referred to as ‘optical isomers’, although we won’t get into this in detail here.
CHFClBr is not the only chiral molecule. Any molecule that contains a carbon atom bonded to four different substituents is chiral. For this reason, chemists often refer to such a carbon atom as a ‘chiral centre’. Other atoms, like nitrogen and sulfur, can also act as chiral centres, if they are bonded to an appropriate number of different substituents.
If a carbon atom is bonded to four substituents that are not all different then the molecule is not chiral. Bromochloromethane (CH2BrCl), for example, is not chiral – it is superimposable on its mirror image, as shown below.
Let’s recap what we’ve learnt about chirality so far:
- A molecule is chiral if it is non-superimposable on its mirror image
- Any molecule that contains a carbon atom (a chiral centre) bonded to four different substituents is chiral
- The two chiral forms of a molecule (left-handed and right-handed) are called enantiomers
Whenever we have only one enantiomer of a chiral material, we have a homochiral substance; homochirality simply means that only one enantiomer is present.
Homochirality in biological systems
Homochirality is quite prevalent in biology. For example:
- 19 of the 20 naturally occurring amino acids exist only in their left-handed form. The 20th (glycine) is non-chiral
- Naturally occurring sugars exist only in the right-handed form
Amino acids and sugars are play hugely important roles in our bodies:
- Amino acids are used to build the proteins and enzymes that help to carry out chemical reactions
- Sugars are the building blocks of polysaccharides, which are used by the body for energy storage. Sugars are also an essential component of DNA
The fact that proteins, enzymes, polysaccharides, DNA and other biologically important structures are made up of homochiral molecules means that they themselves exhibit a form of homochirality.
A single strand of DNA, for instance, has a helical structure. A helix can exist in a left-handed or right-handed form; the two forms are non-superimposable.
In our bodies, only the right-handed form of DNA is present. In other words, our DNA is homochiral. This is because the sugars that form the ‘backbone’ are homochiral. Proteins and enzymes also have homochiral structures because their constituent amino acids are chiral.
The structure of these biological molecules plays an important role in their function. Proteins and enzymes only bind specific molecules and therefore only catalyse specific chemical reactions. The famous DNA double helix can only form because all the individual strands of DNA have the same handedness.
So, homochirality is important in biology, but is it surprising that molecules like naturally occurring amino acids and sugars are homochiral? The answer is yes! To find out why, let’s see what happens when we try to make chiral molecules in the lab.
Chirality in the lab
There are academics and industrial chemists out there who have spent their whole careers synthesising new homochiral materials. One reason for this is that many drugs are homochiral, as they are specifically designed to interact with the homochiral structures in our bodies.
But making homochiral molecules in the lab isn’t always easy. For instance, if we take a non-chiral molecule (let’s call it A) and perform a chemical reaction to make it into a chiral molecule (B), what we end up with is a 1:1 mixture of the left-handed from of B (BL) and the right-handed form of B (BR), as shown below.
The reason we end up with a 1:1 mixture of the right- and left-handed forms of B is because there is no reason for the reaction to form BL rather than BR, or vice versa. The two molecules are chemically equivalent, and the processes involved in their formation are energetically identical.
There are two ways to make the production of one enantiomer favourable – both involve using a homochiral material. We can:
- Use a homochiral catalyst
- Perform a separation using a homochiral material
These approaches are shown below.
In 1.) the homochiral catalyst lowers the activation energy of one of the products (BR or BL), meaning that one hand of B is produced in preference to the other. One enantiomer of the chiral catalyst will favour the production of BR and the other will favour the production of BL.
In 2.) the homochiral material aids separation of the two forms of B. For example, it may be that the homochiral separation agent selectively binds to BL allowing it to be separated from BR.
Often, a combination of these two methods is used. Method 1.) is used to produce predominantly one enantiomer, which is contaminated with a small percentage of the other enantiomer. The small percentage of the unwanted enantiomer can then be removed using method 2.).
The problem
So, to make homochiral molecules in the lab, we need a homochiral catalyst or a homochiral separation agent.
But if that’s the case, where do the homochiral catalysts and separation agents come from? Well, ultimately, chemists make these from naturally occurring homochiral materials, like amino acids and sugars.
But if we can’t make homochiral materials without using other homochiral materials, where did the naturally occurring homochiral materials come from? In other words: what is the origin of homochirality in biological systems?
Although a definitive conclusion about the origin or homochirality in biological systems hasn’t yet been reached, several theories have been proposed. You can read more about these theories here, here and here.