Chemical jigsaw puzzles: how do chemists identify molecules?

Front cover of Great ExplanationsA quick thing before I get into this month’s chemistry ramble: I’m guessing that you, lovely reader, enjoy reading about science stuff. Especially stuff written by an amazing crowd of hard-working science communicators, one of whom is yours truly. So, please consider spreading the word about this awesome book: Great Explanations. Or even better, pledge! There are some fabulous rewards at the different pledge levels. Either way, thank you x

Okay, back to it! Recently, a bit of an argument blew up on Twitter regarding what is, and isn’t, in covid vaccinations. The particular substance du jour being graphene oxide. The @TakeThatChem account pointed out that one of the sources being touted by some as ‘evidence’ for its presence (the article in question was by Robert O Young, remember him? Yes, the one that did actual jail time) didn’t describe the use of any sort of technique that could identify graphene oxide. Which, just to be clear, is absolutely not an ingredient in covid vaccinations.

The debate culminated with questions about how, exactly, scientists do identify substances on the molecular level. @TakeThatChem wondered if one of the users who had become embroiled in the debate even understood how a chemist might work out a molecule’s structure, and then posted an image.

Screenshot of tweet by @TakeThatChem showing an NMR spectrum (link in text)

This tweet illustrated a technique that can be used to identify molecules.

British students of chemistry first meet images like this somewhere around the age of 17–18, so although this is somewhat advanced, it’s still essentially school-level. Which means that for a chemist, it’s one of those things that’s so familiar that, half the time, we probably forget that the rest of the world will have absolutely no idea what it is.

But for those that have never studied A level chemistry or similar: what is it?

The answer is that it’s a proton NMR, or nuclear magnetic resonance, spectrum. Now, NMR is quite tricky. Bear with me, I’m about to try and explain it in a paragraph…

Here goes: you know magnets? And how, if you put one magnet near another magnet, it moves? Now imagine that certain types of atomic nuclei are basically tiny magnets. If you put them in a really powerful magnetic field, they sort of move. If you then alter that magnetic field, they move as the field varies. A computer records and analyses those changes, and spits out a graph that looks like that one back there – which chemists call a spectrum.

Photo of MRI equipment

Medical MRIs use essentially the same technology as the one used to generate the spectrum

Did I nail it? There’s a lot more to this, not surprisingly. In particular, radio waves are involved. My quick and dirty explanation is the equivalent of describing a car as a box on wheels – it’s broadly true from a distance if you squint a bit, but if you said it in the presence of a qualified mechanic they’d wince and start muttering words like ‘head gasket’ and ‘brake discs’ and ‘you do know this is a diesel engine, yes?’

Anyway, it’ll do for now. If you’re studying NMR at a more advanced level, take a look at this episode of Crash Course Organic Chemistry written by… someone called Kat Day. No idea who that is 😉

The same technique, by the way, is used in medicine – but there you know it as MRI, or magnetic resonance imaging. It turns out that if you shove a human (or pretty much anything that contains a lot of carbon-based molecules) into a powerful magnetic field, the atomic nuclei do their thing. You might imagine that having all your atoms do some sort of cha-cha would hurt, but no – as anyone who’s ever had an MRI will attest, it’s mostly just very loud and a bit dull. The end result is an image with different contrast for different types of tissue. Fatty tissue, for example, tends to show up as areas of brightness, while bone tends to look darker – so it’s useful for diagnosing all sorts of problems.

Photo of jigsaw pieces

Interpreting a proton NMR spectrum can be a bit like looking at a jigsaw pieces

But back to chemistry. Chemists, preferring a simpler life (haha), are often working with single substances. Or at least trying to. If we imagine a molecule as a picture, looking at a proton NMR spectrum is a bit like looking at a mixed-up jigsaw puzzle of that picture. Each individual piece – or peak – in the spectrum represents an atom or a group of atoms.

Each piece tells you something and, at the same time, it also tells you about the bits that are joined to it. In the same way that you might look at a jigsaw piece and think, ‘well, this has a sticky-out bit so the piece that goes next to it must have an inny-bit,’ chemists look at a spectrum and say, ‘well, this bit looks like this, so its carbon atom must be attached to group of atoms like that.’

Okay, so what do the pieces in the spectrum @TakeThatChem posted show us? Well, reading spectra takes practice but, like most things, if you do that practice, after a while you get into the habit of spotting things straight away.

For example, it’s fairly obvious to me that whatever-it-is it probably has a carboxylic acid (COOH) group, and it definitely has a benzene ring. I can also see that the benzene ring has things bonded to opposite points, in other words, if you numbered the carbons in the ring from 1 to 6, it has things attached at carbon 1 and carbon 4. There’s a chain of carbons, which is branched, and there’s another CH3 group somewhere. To get more precise I’d have to look more carefully at the integrals (the differently-sized ∫ symbols over the peaks), hunt for a data sheet and study the scale on the horizontal axis along the bottom.

Photo of white pills

The spectrum is of a common drug substance, but which one…

My brain got as far as ‘hm, maybe it’s aspirin, oh no, it can’t be, because…’ before I came across the already-posted answer. I won’t give it away – spoilers, sweetie – but let’s just say it’s a molecule not a million miles different from aspirin.

So yes, chemists do have the means to identify individual molecules, but it requires a fair bit of knowledge and training to both carry out the techniques and to interpret the results. Despite what Hollywood might have us believe, we don’t (yet) have a machine that intones ‘this material is approximately 40% isobutylphenylpropionic acid, captain’ when you plop a sample into it.

The fact that real chemistry (and science in general) is not simple is precisely why pseudoscience peddled by the likes of Robert O Young is so appealing: it’s nice and easy, it follows a sort of ‘common sense’ narrative, it’s not swathed in all sorts of technical language. Anyone can read it and, without any other training, feel as if they understand it perfectly.

None of us knows what we don’t know. If someone comes along with an easy explanation, it’s tempting to believe it – particularly if they go on to play into our anxieties and tell us what we were hoping to hear.

Which brings me to a thread by the lovely Dr Ben Janaway, one tweet of which said, extremely eloquently:

Please do not harass [people protesting covid vaccines]. Please do not blame them. My education is a privilege they have not been afforded. They do not lack intelligence, they lack being taught how to make sense of very complicated things, most of it hidden. What can we do, listen and talk.

Photo of a facemask, syringe and vaccine vials

Please get vaccinated

His point is a good one. All we can do is keep spreading the word as clearly as possible and just hope that, maybe, it will change one mind somewhere. Because maybe that mind will change another, and maybe sense will spread.

Take care, stay safe, and get vaccinated. Get your flu jab, too, if it’s that time of year in your part of the world.


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How are amber teething necklaces supposed to work?

Do amber beads have medicinal properties?

Amber, as anyone that was paying attention during Jurassic Park will tell you, is fossilised resin from trees that lived at least twenty million years ago (although some scientists have speculated it could be older). It takes the form of clear yellow through to dark brown stones, seemingly warm to the touch, smooth and surprisingly hard. It is certainly beautiful. But does it also have medicinal properties? And if it does, are they risk-free?

In 2016 a one year-old boy was found dead at his daycare centre in Florida. The cause of death was a necklace, which had become tangled and tightened to the point that he was unable to breathe.

Why was he wearing a necklace? Surely everyone knows that babies shouldn’t wear jewellery around their necks where it could so easily cause a terrible tragedy like this? No one needs a necklace, after all – it’s purely a decorative thing. Isn’t it?

Yes. Yes, it is. However, this particular type of jewellery was specifically sold for use by babies. Sold as a product that parents should give their children to wear, despite all the advice from medical professionals. Why? Because this jewellery was made from amber, and that’s supposed to help with teething pains.

Teething is a literal pain.

Anyone whose ever had children will tell you that teeth are basically a non-stop, literal pain from about 4 months onward. Even once your child appears to have a full set, you’re not done. The first lot start falling out somewhere around age five, resulting in teeth that can be wobbly for weeks. And then there are larger molars that come through at the back somewhere around age seven. Teenagers often find themselves suffering through braces and, even when all that’s done, there’s the joy of wisdom teeth still to come.

It’s particularly difficult with babies, who can’t tell you what hurts and who probably have inconsistent sleep habits at the best of times. Twenty sharp teeth poking through swollen gums at different times has to be unpleasant. Who could blame any parent for trying, well, pretty much anything to soothe the discomfort?

Enter amber teething necklaces. They’re sold as a “natural” way to soothe teething pain. They look nice, too, which I’m sure is part of their appeal. A chewed plastic teething ring isn’t the sort of thing to keep in baby’s keepsake box, but a pretty necklace, well, I’m sure many parents have imagined getting that out, running their fingers over the beads and having a sentimental moment years in the future.

Amber is fossilised tree resin.

So-called amber teething necklaces are made from “Baltic amber,” that is, amber from the Baltic region: the largest known deposit of amber. It is found in other geographical locations, but it seems that the conditions – and tree species – were just right in the Baltic region to produce large deposits.

Chemically, it’s also known as succinite, and its structure is complicated. It’s what chemists would call a supramolecule: a complex of two or more (often large) molecules that aren’t covalently bonded. There are cross-links within its structure, which make it much denser than you might imagine something that started as tree resin to be. Baltic amber, in particular, also contains something else: between 3-8% succinic acid.

Succinic acid is a dicarboxylic acid.

Succinic acid is a much simpler molecule with the IUPAC name of butanedioic acid. It contains two carboxylic acid groups, a group of atoms we’re all familiar with whether we realise it or not – because we’ve all met vinegar, which contains the carboxylic acid also known as ethanoic acid. If you imagine chopping succinic acid right down the middle (and adding a few extra hydrogen atoms), you’d end up with two ethanoic acid molecules.

Succinic acid (the name comes from the Latin, succinum, meaning amber) is produced naturally in the body where it is (or, rather, succinate ions are) an important intermediate in lots of chemical reactions. Exposure-wise it’s generally considered pretty safe at low levels and it’s a permitted food additive, used as an acidity regulator. In European countries, you might see it on labels listed as E363. It also turns up in a number of pharmaceutical products, where it’s used as an excipient – something that helps to stabilise or enhance the action of the main active ingredient. Often, again, it’s there to regulate acidity.

Basically, it’s mostly harmless. And therefore, an ideal candidate for the alternative medicine crowd, who make a number of claims about its properties. I found one site claiming that it could “improve cellular respiration” which… well, if you’ve got problem with cellular respiration, you’re less in need of succinic acid and more in need of a coffin. Supposedly it also relives stress and prevents colds, because doesn’t everything? And, of course, it allegedly relieves teething pains in babies, either thanks to its general soothing effect or because it’s supposed to reduce inflammation, or both.

Purporters claim succinic acid is absorbed through the skin.

The reasoning is usually presented like this: succinic acid is released from the amber when the baby wears the necklace or bracelet and is absorbed through the baby’s skin into their body, where it works its magical, soothing effects.

Now. Hold on, one minute. Whether this is true or not – and getting substances to absorb through skin is far less simple than many people imagine, after all, skin evolved as a barrier – do you really, really, want your baby’s skin exposed to a random quantity of an acidic compound? Succinic acid may be pretty harmless but, as always, the dose makes the poison. Concentrated exposure causes skin and eye irritation. Okay, you might say, it’s unlikely that an amber necklace is going to produce anywhere near the quantities to cause that sort of effect, but if that’s your logic, then how can it also produce enough to pass through skin and have any sort of biological effect on the body?

The answer, perhaps predictably, is that it doesn’t. In a paper published in 2019, a group of scientists actually went to the trouble of powdering Baltic amber beads and dissolving the powder in sulfuric acid to measure how much succinic acid they actually contained. They then compared those results with what happened when undamaged beads from the same batches were submerged in solvents, with the aim of working out how much succinic acid beads might conceivably release into human skin. The answer? They couldn’t measure any. No succinic acid was released into the solvents, at all. None.

Scientists submerged Baltic amber beads in solvents to see how much succinic acid they released.

They concluded that there was “no evidence to suggest that the purported active ingredient succinic acid could be released from the beads into human skin” and also added that they found no evidence to suggest that succinic acid even had anti-inflammatory properties in the first place.

So amber necklaces don’t work to relieve teething pains. They can’t. Of course, there could be a sort of placebo effect – teething pain is very much one of those comes-and-goes things. It’s very easy to make connections that just aren’t there in this kind of situation, and imagine that the baby is more settled because of the necklace, when in fact they might have calmed down over the next few hours anyway. Or maybe they’re just distracted by the pretty beads.

And, fine. If wearing the jewellery was really risk-free, then why not? But as the story at the start of this post proves, it is not. Any kind of string around a baby’s neck can become twisted, interfering with their breathing. Most necklaces claim to have some sort of “emergency release” mechanism so that they come apart when pulled, but this doesn’t always work.

Don’t fall for the marketing.

Ah, goes the argument. But it’s okay, because we only sell bracelets and anklets for babies. They don’t go around the baby’s neck. It’s completely safe!

No. Because I don’t care how carefully you make it: the string or cord could still break (especially if it’s been chewed), leaving loose beads to pose a serious choking hazard. Not to mention get jammed in ears or nostrils. Even if you’re with the baby, watching them, these sorts of accidents can happen frighteningly quickly. Letting a baby sleep with such an item is nothing short of asking for disaster, and no matter how good anyone’s intentions, babies do have a habit of dozing off at odd times. Will you really wake the child up to take off their bracelet? Every time?

In summary, don’t fall for the marketing. Amber necklaces may be pretty, but they’re not suitable for babies. The claims about succinic acid are completely baseless, and the risks are very real.


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A Dash of Science, Social Media and VARD

Yesterday I recorded a podcast with Matthew Lee Loftus (from The Credible Hulk) and Christopher El Sergio for A Dash of Science, all about science communication and social media. It was a brilliant chat – I won’t go into lots of details of what we covered, but if you’d like to hear it (you know you do!) the direct link is: Communicating Science on Social Media. You can also pick it up on iTunes and/or Tune In.

After our conversation ended I remembered something I developed little while ago, after marking a particularly infuriating research homework where a quarter of the class wrote down that Mendeleev was awarded a Nobel prize for his work on the Periodic Table. For the record: he never received the honour. He was recommended for the prize but famously (at least, I thought it was famously!) the 1906 prize was given to Henri Moissan instead, probably due to a grudge held by Svante Arrhenius of Arrhenius Equation fame (it’s a good story, check it out).

Mendeleev was never awarded a Nobel prize.

Does it really matter if a few students believe that Mendeleev won a Nobel prize? That’s not really harming anyone, is it? Maybe not, but on the other hand, perhaps it’s part of a long and slippery slope greased with ‘alternative facts’ which is leading us to, well, shall we say, situations and decisions that may not be in our best interests as a society.

How to encourage students to do at least a little bit of fact-checking? Of course, you could produce a long list of Things That One Should Do to check information, but I reasoned that while students might read such a list, and even agree with the principles, they were unlikely to get into the habit of applying them and probably quite likely to immediately forget all about it.

Instead I tried to come up with something short, simple and memorable, and here it is (feel free to share this):

Fact-checking isn’t easy; it’s VARD

The four points I focused on spell out VARD, which stands for…

Verify

V is for verify, which means: can you find other sources saying the same thing? Now, chances are, you can always find something that agrees with a particular piece of information, if you look hard enough. There are plenty of sites out there that will tell you that lemons ‘alkalise’ the body, for example (they don’t), that it’s safe to eat apricot kernels (it’s not) and that black salve is an effective treatment for skin cancer (nope).

However, if you’re reasonably open-minded when you start, chances are good that you’ll find both sides of the ‘story’ and that will, at the very least, get you thinking about which version is more trustworthy.

Author

A is for author. I often hear swathes of content being disparaged purely based on its nature. You know the sort of thing: “that’s just a blog,” or “you can’t trust newspaper articles”. I think this is wrong-headed. What matters more is who wrote that piece and what are their qualifications? I’d argue that a blog post about medical issues written by a medical doctor (for example, virtually anything on the marvellous Science Based Medicine) is likely to be a pretty reliable source. Conversely, there’s been more than one thing that’s made it into the scientific literature which has later turned out to be flawed or even flat false (such as Wakefield’s famous 1998 paper). It’s also worth asking what someone’s background is: Stephanie Seneff, for example, is highly qualified in the fields of artificial intelligence and computer science, but does that mean we should trust her controversial opinions in biology and medicine? Probably not.

You may not always be able to tell who the author is, or have time to dig into their motivations, but it’s nevertheless a good question to keep in the back of your mind.

Reasonableness

Be honest: is that story really likely? Or is it just shocking?

R is for reasonableness. Which is a pain to spell or even say, but it’s important so I’m sticking with it. It’s a sense-check. Human beings love a good story, and the best stories have unexpected twists and turns. That’s why medical scare-stories pop up in newspapers with such depressing regularity. No, ketchup isn’t giving you cancer. No, our children really aren’t being poisoned by plastics. But the truth doesn’t always make a good headline. In fact, when it comes to science, the more some ‘exciting finding’ is plastered over news sites, the less you should probably trust it – because the chances are that the exciting version being reported bears almost no resemblance to the researchers’ original conculsions.

Be honest and ask yourself: does this really seem likely? Or would I just like it to be true because it’s a great story?

Date

If a surprising story has just appeared, give it twenty-four hours – chances are if there are major issues with the information someone else will come forward.

D is for date. The obvious situation is when information is so old that it’s been superseded by something else. This is easy: just look for something more recent. However, the other side of this coin is probably more relevant in these days of rolling news and instant sharing of articles: something can blow up at short notice, especially something topical, and it later turns out that not all the facts were known. Take, for example, the famous green swimming pools in the 2016 Olympics, which more than one writer attributed to copper salts in the pool water before the full facts were revealed a few days later. Inevitably, the ‘corrected’ version is far less interesting than the earlier speculation, and so that’s what everyone remembers.

If something controversial and shocking has just appeared, give it twenty-four hours. If there’s something terribly wrong with it, chances are someone will pick up on it in that time.

It’s not easy; it’s VARD

And that’s it: Verify, Author, Reasonableness, Date. It doesn’t cover every eventuality, but if you keep these points in the back of your mind it will definitely help you to separate the ‘probably true’ from the ‘almost certainly bollocks’.

Good luck out there!

Now why not go and listen to that podcast 🙂


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