Molecule of the Day

Editor’s note: Hi all! It’s been a while - but I’m back with a post about how we smell things! This is reposted from a fragrance review + perfumery blog I created, Aromatic Aethers - do consider checking it out and subscribing to it if you enjoyed this post and want to learn more about olfaction/perfumery, or are simply passionate about fragrances :)

Envision yourself in an endless hallway with countless locked doors. Behind each door is a room filled with a scent - vanilla, jasmine, sea spray, you name it - even some that you've never smelled before in your life!

Each lock is unique, but it doesn't require the key to be a perfect fit to be opened; as long as the key is of roughly the right shape and size, it'll be able to open the door, sending the hallway awash with its contained aroma - and sometimes, even an unfurled paperclip would suffice.

In some cases, the locks are similar, too - a key that opens one door can open some others, and as the scents mix in the hallway, you pick up a mixture of smells.

That is the lock-and-key mechanism of olfaction; the keys are the molecules that make their way into your nose, which are known as ligands, and the locks are the olfactory receptors in your nasal cavity, which have a complex 3D structure that the ligand will need to be complementary to in order to bind.

Just like regular keys, the teeth are what controls whether the key will be able to turn the lock; that is analogous to the osmophore and profile, key parts (see what I did there?) of the molecule which enables it to be inserted into and bind to the receptor, triggering nervous signals that your brain interprets as a scent. Without it, the ligand would be completely unable to engage the receptor.

On the other hand, while necessary for the functioning of the key, you could get away with a locksmith making you a duplicate key with a slightly misshapen stem - the key would probably still be able to fit inside the lock, and as long as the tip can be inserted and the teeth line up with the mechanism, you'll be able to open the door - given that the stem isn't completely out of shape or of the wrong size. This is akin to the rest of the ligand besides the osmophore and profile.

(Note: While the lock-and-key analogy suggests an all-or-none response, the "stem" in odourants or the positioning of the osmophore can help the molecule achieve better binding, which in turn triggers a stronger response - so imagine a key with a poor fit allowing you to open the door by a gap and pick up wisps of the aroma, while a perfect fit would enable you to throw the door wide open, completely flooding the hallway with its scent.)

As you can see, the molecular structures of limonene, which smells like citruses, and cedrol, which is found in cedarwood, which look nothing alike, also smell nothing alike - cedrol is too large to fit into the limonene receptor, while limonene can't achieve good binding to the cedrol receptors as the teeth of the key don't match.

On the other hand, considering beta-santalol, which is one of the principal odourants of sandalwood, and sandalore, which is a synthetic molecule but also smells like sandalwood, you can see that they share a similar general shape; a bulky cyclic structure on one end of the molecule and an OH group on the other, separated by a chain of carbon atoms (they look just like keys, don't they?). This allows them to both fit into the same receptor and elicit the same response from our brain ("oh, this smells like sandalwood!").

With the knowledge of the receptor's shape, new odourant molecules can also be designed, and may even achieve better binding than the natural ligand - javanol, for example, is an extremely powerful sandalwood molecule that was discovered through intentional molecular design.

Back to the titular question: What makes a rose smell like a rose?

If you analysed the components of rose oil, you'd find that it has myriad compounds that contribute to its scent - citronellol, geraniol, phenylethyl alcohol, beta-damascone... You get the idea. None of them are singularly responsible for the complex, rich scent of roses, but instead contribute to the various olfactory facets that rose possesses - lemony, floral, balsamic, et cetera. It is important to note that smells are usually highly complex mixtures of hundreds or thousands of molecules, and oftentimes, no single molecule can realistically replicate a natural scent.

If you attempted to recreate the scent of a rose by taking the most abundant molecules like geraniol and phenethyl alcohol, you'd end up with a rather flat caricature; somewhat counterintuitively, relative abundance isn't correlated to the impact that they have on the overall scent! That is why even though citronellol makes up 38% of rose oil, it's only responsible for 4.3% of the olfactory impact, whereas beta-damascenone is a trace component (0.14%) but is responsible for 70% of the olfactory impact (Source: Scent and Chemistry, by Ohloff, Pickenhagen, and Kraft)!

This caused a lot of headaches for chemists a century ago, as they only had the techniques to identify the more abundant compounds back then, and were thus unable to convincingly recreate the scent of roses as a cheaper alternative to rose oil!

While analytical techniques have advanced immensely since then, many questions remain - even a commonly used perfumery material like vetiver oil only recently had its odour principle, which is present in trace amounts, discovered by Kraft et al. Nevertheless, new discoveries are being made every day, and I'm excited to see what the future brings!

Photo sources: [1] [2] [3] [4, 5 - my own] [6]

I’m pretty sure that everyone knows about COVID-19 (Coronavirus Disease 2019) by now - it has just been declared a pandemic by the World Health Organisation (WHO). But how does it infect our cells, and how can we protect ourselves against it?

Pathology

As with many other viruses, COVID-19 works by docking itself onto cellular receptors - in this case, angiotensin-converting enzyme 2 (ACE2). A spike protein on the virus binds to ACE2, allowing it to enter the cell - this pathway bears some similarities to the related virus which resulted in the 2003 SARS outbreak. As ACE2 is most commonly found in the respiratory system, the most serious symptoms are often respiratory in nature.

Symptoms include fever, dry cough, fatigue, phlegm production, and shortness of breath amongst others.

When the virus releases its genetic material into the cell, its genetic material directs our cellular machinery to synthesise viral proteins and replicate its RNA, which assemble in the cell and are released into the extracellular environment when formed, allowing the virus to be spread to other cells. The host cell may also eventually burst and die. 

Preventive measures

As COVID-19 is a virus, antibiotics do not work against it; antibiotics work by targeting bacterial structures or processes, which are are not present in viruses. 

Alcohol, on the other hand, works against both bacteria and COVID-19. This is because they have phospholipid bilayers surrounding them, which are dissolved by alcohol. This mechanical disruption of the viral envelope results in the virus being unable to merge with our cellular membrane and release its genetic material into our cells. Soap also acts as a disruptor of phospholipid membranes - which is why even non-antibacterial soaps are effective at slowing the spread of COVID-19. It is advised to wash your hands with soap regularly (for at least 20 seconds) and to use hand sanitiser if hand washing is not possible.

As COVID-19 is spread by respiratory droplets which can be produced by breathing, speaking, sneezing, and coughing amongst other ways, it is advised to avoid unnecessary human contact and to wear face masks if sick. Sneezes and coughs should be covered with tissue paper, which should be disposed of immediately. While there have been reports that COVID-19 can be spread by asymptomatic carriers, it is believed that it is most likely to be spread by symptomatic patients. 

What do I do if I’m sick?

If you’re in the US or UK, visit the links below and follow the instructions/guidance if you are sick; for other countries, please visit your country’s health ministry’s website for further guidance.

US: CDC - Prevent the spread of COVID-19 if you are sick

UK: NHS 111 - About coronavirus (COVID-19)

To all readers, please take all necessary precautions and stay safe! Wishing you the best of health. xx

Photo credits: [1] [2] 

Reference: [1] 

The drug propranolol (D, C16H21NO2), which is used to treat high blood pressure and anxiety, can be synthesised from 1-methoxynaphthalene through the following pathway.

Identify the unknowns A to D, and draw the mechanisms of each step.

What smells do you associate with “cleanness”? Is it the clean, dewy freshness after a thunderstorm (due to geosmin - Day 14)? Or is it that warm, enveloping smoothness of clean linen?

If you’re thinking about the latter, Galaxolide (C18H26O) is probably responsible for that. It belongs to a class of compounds called “musks”, which are extremely commonly used in fragrances, from functional (detergents and soaps) to fine (perfumes). 

Musks used to be obtained from musk pods - a gland of musk deer - since ancient times, when they were discovered to not only have an aroma of their own, but also acted as a fixative for fragrances, which is to say that it prolonged the lasting power of fragrances that it was added to. Natural musk can also be obtained from civet cats and muskrats, amongst other animals.

However, in recent decades, the industry has turned to synthetic musks due to sustainability and ethical concerns regarding the harvesting of musk pods.

The first synthetic musks were discovered serendipitously in the late 19th century; a chemist, Albert Bauer, was trying to find a more explosive analogue to trinitrotoluene (TNT - Day 58) when he noticed that the products of his experiments had a pleasant musky odour. These “nitro musks”, as they were called, found widespread use due to their relatively low costs and similarity to natural musk. Chanel famously used nitro musks in many of their perfumes, including No. 5.

However, nitro musks were eventually suspected of neurotoxicity, and were phased out; only one nitro musk, musk ketone, is currently approved to be used in the fragrance industry.

Other types of musks - macrocyclic musks, such as muscone and civettone, were isolated from natural musk from musk deer and civet cats. However, industrial synthesis proved too complicated and commercially unfeasible for the early 20th century.

The hunt for a new type of synthetic musk - one that was safe and cheap - was on again. In 1965, Galaxolide was first synthesised by International Flavors and Fragrances (IFF) in an attempt to make existing musks more chemically stable and hydrophobic, and was quickly utilised in many functional and fine fragrances due to its crisp, clean connotations; it was completely free of any animalic nuances, unlike molecules like muscone.

Why does the molecule have to be hydrophobic? Consider its purpose - when used in detergents, it would be a desirable quality to be able to adsorb onto fabric fibres and not be washed off by water. Its relatively large size meant that strong intermolecular forces of attractions would lead to low volatility too, thus allowing it to impart a long-lasting pleasant smell.

While Galaxolide was not the first polycyclic musk to be discovered, it is by far the most well-known one and is produced on a scale of 1,000 tons a year as of 2015.

However, with its ubiquity, its persistence in nature and its tendency to bioaccumulate has been brought under scrutiny. While no toxic effects to humans have been reported, it has still been a cause for concern as its effects on wildlife are not well understood.

And the search for new affordable, safe, and biodegradable musks continues...

My dear readers - what chemicals have you tried sniffing? Which ones had a nice aroma, and which ones smelled awful? Let me know in the comments!

Here’s an organic chemistry question I set that y’all can try out! Reblog this post with your answers if you want to attempt the question - I’ll try and let you know how you’ve done, or if I have any comments on your answers :)