Download Life Through the Looking-Glass: Reflections Aren`t Always What

Life Through the Looking-Glass: Reflections Aren’t Always
What They Seem
By Emma Durham
“Perhaps Looking-glass milk isn’t good to drink” – Alice, Through The Looking-Glass
Lewis Carroll touched upon the idea of chirality in 1898, in Through the Looking
Glass, with the idea that reversed items may be
different from the originals. Alice was
sensible to question this mirror image
milk, as the molecules within it could
have a profoundly different effect on
her body. By taking the sugar galactose
from milk and chemically converting it
into its mirror image, you get Tagatose.
Even though Tagatose is just as sweet
as sugar, your body cannot process it,
and in 2001 the FDA approved it for use as
an artificial sweetener. Alice missed out on discovering diet milk!
Let’s take a few steps back. What exactly is chirality?
“I call any geometrical figure, or group of points, 'chiral', and say that it has chirality
if its image in a plane mirror, ideally realized, cannot be brought to coincide with
itself.” – Lord Kelvin, 1893
Derived from the Greek word kheir meaning
hand, indeed the easiest way to think about
chirality is to look at your hands. Both are the
same size, have four fingers and a thumb.
However, they are mirror images of each
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other. No matter what you try, you can’t overlay them, which is why your left hand
will only fit in your left glove. The same can apply to drugs - one version of a drug will
be active, but the mirror image may have no effect, or even a fatal effect. These
mirror images are known as enantiomers. Before looking at chirality on the
molecular level, let’s look at it displayed on a macroscopic level, in bodies of living
things.
Chirality and Genetics
Reiko Kuroda, the first female professor at the University of Tokyo, devised
innovative experiments to show how chirality is genetically determined. In a time
where there was no support for women in science in Japan, Kuroda was encouraged
to find a partner and marry 1. As Pembroke College celebrates 30 years of admitting
women, it is important to note how Kuroda managed to defy cultural gender
expectations and pioneer the way for women in Japan, winning the L’Oréal–UNESCO
for Women in Science award in 2013.
Most vertebrates do not have
internal symmetry. This means
that the location of organs,
including the heart, can be either
side of the body, giving rise to
leftKuroda
and
right-handedness.
demonstrated
that
during embryonic development, when at the eight-cell stage, the handedness of the
snail could be reversed. Kuroda achieved this by prodding the cells gently with a
glass rod- disrupting the action of the nodal gene. This is the first example of
reversing the chirality within an organism. Interestingly, when the snails reproduced,
the offspring reverted back to the original “handedness” of their grandparents,
meaning the action of the gene had been altered but not the actual gene itself 2, 3.
Kuroda’s work opened a whole new area of research upon genetic chirality.
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This reversal can also occur in humans; there is a 0.01% chance of an individual being
born with what is known as situs inversus where some, or all, of the internal organs
are on the opposite side. It can occur with twins, meaning some twins are actually
mirror images of each other!
Chirality on the Molecular Level
Most people associate the name Louis Pasteur with the pasteurisation of milk.
Pasteur managed to revolutionise our understanding of bacteria, and created the
first vaccines for rabies. However, Pasteur also worked on chirality, performing the
first chiral separation and introducing the idea of isomerism into the field of science.
Pasteur focused his work on tartrates – a
group of compounds that contain two acid
groups. Looking at the effect of tartaric acid
crystals on rotating the plane of polarised
light, he discovered that acid obtained
naturally from fermenting wine contained a
single enantiomer. In contrast, synthetic tartaric acid contained a 50:50 mixture.
Upon inspection of the synthesised acid under
a microscope, Pasteur discovered that the
crystals were actually mirror images of each
other.
Demonstrating
incredible
patience,
Pasteur used a microscope and a pair of
tweezers to separate the different enantiomers
and prove that although they had the same
chemical composition, they were indeed structurally different to each other 4.
So despite being an incredible feat of human determination and curiosity, why
would one go through such an effort? It turns out that the chirality of molecular
compounds has proved to be incredibly important in how effective drugs can be in
the body.
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Chirality in Pharmaceuticals
Thalidomide was a drug that first became available in 19575. Marketed to pregnant
women suffering from morning sickness, the drug became popular across the globe.
Tragically, this drug turned out to be a teratogen – meaning that the infants were
born with malformation of the limbs, with a mortality rate of 50%. This crisis
occurred due to the marketing of the drug as a 50:50, or racemic, mixture. One of
the enantiomers indeed eased the morning sickness of the women, whereas the
other enantiomer caused the catastrophic effects. Unfortunately, due to the
reactivity of the molecule, isolation of the desired enantiomer to be sold as a drug is
futile, as enzymes in the body can convert it to the opposite enantiomer anyway!
= Carbon C
= Hydrogen H
= Nitrogen N
= Oxygen O
Structure on left: one enantiomer of thalidomide with 5-membered ring “pointing
down” compared to the hydrogen on the carbon, represented by the dashed wedge.
Structure on right: the other enantiomer of thalidomide with 5-membered ring
“pointing up” compared to hydrogen on the carbon, represented by the bold wedge.
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However, different enantiomers don’t always have this detrimental an effect on the
human body. Available over the counter, ibuprofen is sold as a racemic mixture. As
with thalidomide, only one of these enantiomers is potent in the quantity sold, with
the second enantiomer not being biologically active. Luckily, the two enantiomers do
not need to be separated to increase the efficacy of the drug. An enzyme exists in
the body that converts the inactive enantiomer to the more active one, meaning the
drug is extremely effective as a mixture.
Thalidomide blocking the action of a protein involved in foetal development.
But how does this work? In modern-day chemical design, many compounds are
designed with chirality in mind. Most enzymes and proteins in the body won’t be
planar: they will have 3-dimensional active sites, which explains why some
enantiomers have an effect while others, like artificial sweeteners, will have no
effect – they simply might not fit into the active site. As seen earlier, organisms
themselves can be chiral, but it isn’t just the positions of the organs; the molecules
making up the human body are chiral themselves.
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Chirality and Life
Amino acids are a group of compounds that make up proteins, occurring in every cell
in every part of your body. A protein chain consists of a combination of amino acids
forming intricate 3D structures, which can only form when built from molecules that
possess the same chirality. There are 20 naturally occurring amino acids, which are
all found to be left-handed. It has been shown that a mix of the different
enantiomers of amino acids would not be successful in creating living things; life is
only possible due to homochirality. However, mystery lies in why life on Earth
favours these left-handed proteins, when theoretically life could exist based entirely
on right-handed amino acids.
Recent evidence has
suggested that this lefthandedness may have
been
influenced
by
meteorites. For life to
have a preference for
left-handed
chirality,
there must have been
an
excess
of
left-
handed amino acids at
some
Earth’s
point
in
the
history.
The
Murchison
meteorite
fell in 1969, and was
found to contain 15 of
the amino acids found
on the Earth. Most of these were 50:50 mixtures; however, the left-handed version
of the amino acid isovaline was found to be in slight, but significant excess. Isovaline
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is rare in biology, but very common in meteorites. This would increase the lefthanded amino acid availability, nudging life to be left-handed.
There are several explanations proposed as to why there is an excess of left-handed
amino acids in meteorites, ranging simply from contact with water to things as
complex as radiation from neutron stars6. Bringing ourselves back down to Earth,
something more relatable is how odours are affected by chirality.
Chirality and Smell
It has long been known that chiral
molecules have different odours.
Menthol, for example, is an additive
in medicines and confectionaries.
Occurring naturally in peppermint
oil,
it
exists
mainly
as
one
enantiomer (out of a possible 8
isomers). This is the only one to give
the cooling sensation upon ingestion or contact that we are familiar with, for
example in Vick’s vapour rub. However, there is a much higher demand for this type
of menthol than can be found from natural sources. In 2001 Ryoji Noyori won a
Nobel Prize for his work on developing a way to make the desired type of menthol
without any of the other enantiomers.
Different enantiomers can have extremely different fragrances – as with the
essential oil carvone. Again, existing in pure enantiomers in nature, the two
enantiomers have very distinct smells and tastes. One enantiomer of carvone has a
strong smell of peppermint, whereas the other enantiomer smells like caraway.
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Life Through the Looking-Glass
“Then fill up the glasses with treacle and ink,
Or anything else that is pleasant to drink:
Mix sand with the cider, and wool with the wine-And welcome Queen Alice with ninety-times-nine!”
-Alice, Through the Looking-Glass
So what would life be like through the looking-glass? For its inhabitants, everything
would seem normal. Their bodies, built from right handed amino acids, would have
evolved to deal with looking-glass molecules. A visitor to this land would experience
things very differently. Peppermint chewing gum making your breath smell like pilau
rice would be the least of your worries! Imported looking-glass milk may be eligible
for sugar free labelling, but as a natural product is likely to have a range of chiral
molecules. Based on Alice’s behaviour in looking-glass land, perhaps one of those
molecules was slightly hallucinogenic…
1
The Royal Society of Chemistry, accessible at http://www.rsc.org/diversity/175-faces/allfaces/professor-reiko-kuroda-0
2 New Scientist, accessible at http://www.newscientist.com/article/dn18203-how-to-windsnail-shells-up-the-wrong-way.html#.VST6_RPF_3q
3 Nature journal, accessible at
http://www.nature.com/nature/journal/v462/n7274/full/nature08597.html
4 Chemistry Explained, accessible at http://www.chemistryexplained.com/Ny-Pi/PasteurLouis.html
5 Science Museum, accessible at
http://www.sciencemuseum.org.uk/broughttolife/themes/controversies/thalidomide.aspx
6 Science and Reason, accessible at http://scienceandreason.blogspot.co.uk/2008/05/aminoacid-chirality-mystery.html
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