Articles by: nickuhlig

The chemistry of William Gibson’s Neuromancer.

Ninsei, courtesy of Vincenzo Natali via twitter.

Note: minor edits made due to incorrect usage of “amphetamine” to refer to crystal meth. This was a typographical error and some explanation has been added to that paragraph for clarity’s sake. My apologies. -N

I recently purchased a new hard copy of William Gibson’s first novel (and sci-fi classic), Neuromancer. I make no secrets about this book being my favourite of all time, and I’ve even got an ongoing project wherein I’m composing a musical companion to the book (progress is slow). While there have been rumours of this book getting made into a movie for at least 10 years now, the project seems permanently stuck in development hell. But the same could be said of Altered Carbon several years ago, and look where we are now!

Apart from inventing the term “cyberspace” and predicting virtual reality long before it became commonplace, Neuromancer also contains some interesting tidbits of chemistry. Being a chemist myself, specifically one in the pharma industry, these little nuggets of scientific prose jump out at me, and quite pleasantly Gibson (for the most part) does a good job of using them appropriately. I wanted to examine the pharmaceutical elements of the book, which are almost entirely used by Case and Peter Riviera, its two biggest junkies.

Octagons: “dex”

Dex is a shorthand name for dextroamphetamine. Anyone familiar with the structure of methamphetamine will recognize that it is almost the same molecule–it’s simply missing one methyl group. To be even more specific, dextroamphetamine is a single enantiomer of amphetamine.

In chemistry, molecules that have the same chemical formula are known as “isomers” of each other. This broad term means that the constituent atoms are the same in number and composition, but that the molecules themselves are different in structure in some way. There are many sub-classes of isomer, one of which is enantiomer. This term refers to molecules which are mirror-images of one another, but which cannot be superimposed. The easiest analogy for this would be your hands. Hold them up so that your palms face you and your pinky fingers touch. Ignoring minor differences, they are clearly mirror images of one another. But now turn over your right hand. Your thumbs point the same way and your hands could overlap, but they clearly are not superimposable: your knuckles bend in different directions, your palms face different ways, and so on. These are enantiomers. Likewise, look at dextroamphetamine and levoamphetamine:

Dextroamphetamine (left) and levoamphetamine. Note that Dextroamphetamine is actually the S enantiomer, but is named for the direction in which it rotates polarized light.

Dextroamphetamine (right) and levoamphetamine. Note that Dextroamphetamine is actually the S enantiomer, but is named for the direction in which it rotates polarized light.

The dashed bond on each hydrogen indicates that it is projecting away from the viewer. The only difference in structure between these two molecules is the “chirality” (which comes from the Greek word for hand, transliterated roughly as “kheir”) of that carbon center connecting the benzyl, methyl, NH2, and hydrogen.

Interestingly, dextroiamphetamine (which is in fact the S-enantiomer!) is the more active of the two in the human body, with effects including increased concentration, CNS stimulation, and in higher doses, euphoria and libido enhancement. Street amphetamine methamphetamine (crystal meth, or simply meth) is almost always a mixture of the two enantiomers of methamphetamine, because isolating a single enantiomer usually requires more advanced equipment, more time, and more money. The same is true of amphetamine, which back when it was still either legal or commonly encountered as a street drug (often known as benzedrine, or “bennies”) was usually had as a racemate. Enantiomerically pure dextroamphetamine is used in drugs for narcolepsy and ADHD. Most people are probably familiar with the drug Adderall, which is a 3:1 mixture of dextroamphetamine and levoamphetamine. There are other drug products which use different ratios, the most well-known of which is probably Dexedrine, which is a 100% dextroamphetamine sulfate formulation.

Thus, when Case takes “Brazilian dex”, he is quite simply imbibing a powerful CNS stimulant that has been known for decades and used by everyone from beat poets to fighter pilots and college students.

Case’s new pancreas & the plugs in his liver

Early in the book Case undergoes a highly invasive (though mostly unspecified) set of surgeries to allow him to “punch deck” and resume his career as a virtual reality hacker. During this surgery he has a “new pancreas…and plugs in [his] liver” installed, which make him incapable of getting high on cocaine or amphetamines (including his beloved dex). How involved the pancreas is in the metabolism of these drugs is not known to me, but presumably the plugs in his liver would do one (or all) of the following things:

  1. Severely amp-up his body’s production of monoamine oxidase (MAO) which is the primary mechanism for the metabolism of amphetamines and other psychoactive alkaloids like phenethylamines and tryptamines;
  2. Up-regulate expression of cytochrome p450 (CYP450) enzymes in the liver, which are probably the most important class of xenobiotic-metabolizing enzymes, using oxidation to modify foreign compounds and make them more excretable;
  3. Up-regulate his body’s production of esterases, which as it happens are the main enzymes responsible for the first line of cocaine metabolism and elimination;
  4. Some other type of hand-wavy metabolism-altering or endocrine-altering thing.

MAO is a frequent culprit in the lack of oral bioavailability of alkaloid drugs. Dimethyltryptamine (DMT) for instance, has almost no oral bioavailability because MAO-A is abundantly present in the digestive tract and oxidizes it before it can be absorbed into the blood stream and carried to the brain. Ayahuasca, a South American traditional entheogenic drug, involves ingesting DMT along with a MAO inhibitor, which allows the powerful and profound psychedelic experiences used in shamanistic rituals, all with the relative convenience of an oral administration (YMMV). In Case’s world this particular bit of homebrewed combination therapy wouldn’t be necessary since almost everyone uses “derms” to dose themselves, meaning the gastrointestinal levels of MAO wouldn’t be a concern as the drug would go straight to the bloodstream.

CYP450 is another one that you may come across from time to time. It is responsible for doing the lion’s share of xenobiotics in the human body. These enzymes are highly concentrated in the liver, and generally deal with drugs in one way: oxidation. What this does is (very generally) to become more water soluble, allowing excretion via the renal system and urinary tract. One reason you may have heard of it is that a certain blockbuster drug named Lipitor has some unusual contraindications. People taking this drug (which is a statin inhibitor) are told not to ingest large quantities of grapefruit. The reason for this is that grapefruit and grapefruit juice contain a relatively potent class of CYP450 inhibitor called furanocoumarins, which causes the Lipitor to hang around in the body unmetabolized (and therefore performing its intended function) longer than it should, which can cause problems. CYP450 is also produced in the pancreas, relevant to the current discussion.

Esterases are again a liver-localized family of enzymes that–you guessed it–cleave esters. Cocaine is primarily metabolized by esterases in the liver to produce benzoylecgonine, which is identical to cocaine except for the cleavage of the methyl ester:

Cocaine (left) and benzoylecgonine.

Cocaine (left) and benzoylecgonine.

A less prevalent but still important transformation is the cleavage of the benzyl ester to produce ecgonine methyl ester. Both of these modifications are quite rapid, and responsible for cocaine’s notoriously short duration of effect: roughly 30 minutes after insufflation. While the metabolites hang around for longer, they don’t possess cocaine’s “desirable” effects. Cocaine is also metabolized to a lesser extent by enzymes like CYP450 to produce metabolites with -OH groups on the phenyl ring.

So the “new pancreas and liver” thing is actually not completely outlandish, though of course we get nothing else by way of in-depth explanation, so we can chalk this one up to the vagaries of good science fiction writing: just enough to make it seem doable without so much detail that it begins to fall apart.

Riviera’s cocktail

We’ve already discussed cocaine, and most are probably familiar with its effects, even if not first hand. meperidine, however, is probably better known by its trade name Demerol (or possibly its alternate name pethidine). Meperidine is an analgesic synthetic opioid, though it bears no resemblance to naturally-derived opioids like morphine, heroin, hydromorphone (Dilaudid), or codeine, all of which containe the characteristic fused ring structure at their core (we’ll get into the structures later on in the post). Meperidine and other synthetic opioids are so named simply because they also bind to the opioid receptors in the brain.

This means that meperidine is, like other opioids, an analgesic sedative and CNS depressant. It is commonly used in labour for pain management (administered primarily via IV, and not by epidural).

So as the Finn says, Peter is a speedball artist. He mixes cocaine with an opioid to get his desired blend of highs, much like some people choose to mix heroin and cocaine. And as Peter says, “If God made anything better, he kept it for himself.”

Similar to dex, this is a pretty pedestrian drug reference, but it’s still nice that Gibson gets it right.

Avoiding SAS: scopolamine

When Case makes his forst foray into space with Molly, Peter, and Armitage, he suffers from space adaptation syndrome, or SAS. Basically a nice way of saying motion sickness coupled with weightlessness and your guts being in positions they’ve never been before. So like anyone who experiences these symptoms, he uses a transdermal scopolamine (L-hyoscamine) patch.

This one is actually the least imaginative (or most grounded in reality) of the bunch, because these exist now, and have for years. Scopolamine is used to treat motion sickness and is typically used as a transdermal patch. This is because its oral bioavailability isn’t great (less than 30%), and the patch allows a slow release over the course of three days, very handy if you’re on a boat and know you won’t be leaving for a while.

The kink here, though, is that scopolamine belongs to the class of drugs called tropane alkaloids, of which cocaine is also a member. The name “tropane” refers to the bicyclic nitrogen-containing core at the center of these molecules. This can be seen below at left, on its own, and in cocaine (second from left), atropine (second from right) and scopolamine (right).

tropanes

Tropane (left), cocaine (middle left), atropine (middle right), and scopolamine.

So if Case is incapable of getting any effects from cocaine, would he really be able to benefit from scopolamine’s inhibition of the muscarinic receptors? The answer would appear to be “No” if we take into consideration the most likely ways in which Case’s endocrine and hepatic system have been juiced up. As previously mentioned, cocaine’s most prevalent routes of metabolism are via esterase cleavages of the methyl and benzoyl groups. Scopolamine’s benzoyl group shuold be similarly susceptible. Also, since, unlike cocaine, scopolamine does not possess a methyl ester on its tropane ring, another principal path of metabolism appears to be via CYP450 enzymes in the liver which remove the N-methyl group, making it more water soluble.

So in this particular case, it seems like Gibson may not be correct. Scopolamine most likely would not be able to get past Case’s boosted xenobiotic metabolism. The consolation prize, however, is that he was probably quite right that “the stimulants the manufacturer included to counter the scop” almost certainly wouldn’t, either: they’re probably things like ephedrine or pseudoephedirine (both amphetamines, interestingly these ones are diastereomers of each other), or possibly phenylephrine (structurally very similar to pseudoephedrine).

Case’s angry fix: beta-phenethylamine

While visiting Freeside, Case decides he wants to get high, really, really badly. Luckily he meets a woman named Cath, who happens to be almost permanently dusted on something she calls “beta-phenethylamine”. Case tries a taste and it does the trick not once, not twice, but three times throughout the remainder of the novel, albeit accompanied by hangovers so grievous that it’s a wonder Case makes it through dinner and a show, let alone the cyberspace run of a lifetime.

Here Gibson quite clearly took artistic license with his chemistry, and I don’t necessarily blame him. Beta-phenethylamine refers to an extremely broad class of compounds (of which amphetamines are the best-known members), similar to how “tropane alkaloids” does. The beta-phenethylamine core can be seen below:

phenethylamine2dcsd-svg

Phenethylamine.

This simple arrangement of atoms is such fertile ground for psychoactive compounds that the late, great chemist Alexander Shulgin wrote a book on it. Other well-known compounds in this class include mescaline, MDMA, and the 2C-X series of drugs (where X can be substituted by bromine, iodine, an ethyl group, or even a thioether). So one might be inclined to think that this vagueness allows Gibson to cover his bases without getting painted into a corner, chemically speaking.

Alas, any and all compounds in this class would almost certainly not be metabolized any differently than an amphetamine, as they all have that tricky NH2-CH2-CH2-phenyl skeleton, which is a prime target for MAO. Based on what we’ve assumed about his surgical enhancements, Case almost certainly would not get wasted on this drug or any in its class.

Sorry, Case.

Peter’s downfall: the meperidine hotshot

As we mentioned before, Peter is a speedball artist. One of the drugs he uses is called meperidine. Meperidine is relatively easy to synthesize, and as we know still sees a lot of use in modern times. A drug that is perhaps less known, however, is one of its structural isomers, called MPPP. You can see the two structures below (meperidine at left, MPPP at middle left).

Meperidine (left), MPPP (middle left), MPTP (middle right), and MPP+.

As you can see, very similar. But the subtle change in the ester configuration results in different reactivity under certain circumstances. In brief, MPPP is very easy to decarboxylate by overcooking it or exposing it to moisture (or even better, both). In addition, MPPP’s penultimate intermediate is the free alcohol, which can easily dehydrate. When either of these things happens, something called MPTP is produced, seen above at middle right. MPTP is more correctly called N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, as Molly chants out late in the novel.  MPTP itself is oxidized by MAO in the body to form MPP+ (N-methyl-4-phenylpyridinium) seen at right. Both MPTP and MPP+ are neurotoxins, but MPP+ is the stronger of the two, being highly toxic to dopamine neurons in the substantia nigra of the brain.

A very unfortunate and imprudent graduate student in the 1970s (1976 to be exact), Barry Kidston, self-injected a preparation he had made of MPPP (at the time a legal “designer drug”) which apparently had gone slightly awry, and almost immediately began exhibiting symptoms akin to those of Parkinson’s disease (one in which dopamine is present in chronically low amounts in the brain).  His symptoms were successfully treated with L-dopa (a known treatment for Parkinson’s) for a time. His case was not unique; in fact this phenomenon was observed several more times and a book was written about it by the neurologist who helped to treat some Bay-area addicts with these same symptoms as late as 1982. Interestingly, MPP+’s chloride salt is still used today as a herbicide under the name cyperquat. As for Kidston, he seemed rather determined in his drug use, and was found by his parents catatonic and drooling on September 4th, 1978.  After a brief stay at home, he left, and promptly overdosed on cocaine, which finally proved fatal.

Unfortunately for Gibson, the decarboxylation side reaction to produce MPTP only occurs in the synthesis of MPPP, and not in that of meperidine. The carboxyl group in meperidine is connected to the piperidine ring via its carbonyl carbon, as opposed to the oxygen as in MPPP. This means that if it hydrolyzes, it simply produces the free acid. It can be exceptionally difficult to get this type of structure to decarboxylate, so much so that there are numerous publications with it as their aim.

This is not universally true: THC, perhaps the most commonly-imbibed illegal drug in the world, is actually a decarboxylated product of THCA, tetrahydrocannabinic acid, which is how most THC is found in plants. This decarboxylation is facile, requiring only heat and time. But meperidine is not THC, and such reactions tend to be very sensitive to specific moieties in the molecular structure (in THCA’s case, the phenol -OH adjacent to the carboxylic acid in question).

So in this case Gibson unfortunately got the chemistry very slightly wrong. This can easily be forgiven: such structural isomerism has tripped up many a fledgling chemist, and indeed, sometimes even the pros get it wrong.

As for all the effects of MPTP, Gibson totally nails it. It absolutely does cause Lewy bodies or similar structures to form in the substantia nigra of the brain, its symptoms are like Parkinson’s disease, and it would almost certainly result in death if used for an extended period of time with no treatment. One has to wonder, though, if Peter would notice that he was being poisoned or not. Cocaine, the kicker in his speedball concoction, is a dopamine reuptake inhibitor, which in the short term might counter-act the effects of the MPTP. In the long term however (and we’re talking years probably) cocaine is suggested to contribute to the onset of Parkinson’s. Barry Kidston apparently noticed the effects of his own mistakes almost immediately, and it’s not clear exactly when Peter starts taking the poisoned drugs in the first place. So this is a big old “who knows?”

Wrap-up

Overall Gibson does better than most would. He gets the chemistry about half right, and does a bit of handwaving in a few parts. He even steps into some pharmacology and doesn’t do too badly.

I’d be willing to bet that a lot of this is owed at least in part to his known penchant for dabbling in drugs in the past, but no matter where it comes from, it’s pretty impressive.

Just one more reason why this book remains my favourite of all-time, and why I recommend that everyone read it. Not that I need any more reasons.

 

This post was adapted, expanded, and improved from an earlier post on my personal blog.

By April 16, 2018 17 comments Uncategorized

Chemistry-themed Valentine’s Day Cards – Round Three

You're a freak in the sheets!

An example of my typical brand of (bio)chemical humour.

 

Happy new year, everyone! It’s been a long time since I’ve posted here at the chemistry blog, but as a totally-not-a-New-Year’s-resolution I’ve decided I’d like to resume posting here at least semi-regularly.

A few years ago I had a minor burst of artistic creativity. This primarily concerned chemistry-theme puns of a mildly romantic nature. Having recently defended my PhD and with a glorious eight weeks of pure, unadulterated freedom in hand until I started my first job, I sat down and drew out some sketches that later turned into actual, real Valentine’s Day cards.

I posted them to reddit and had a pretty good response. Chemjobber posted about them on their blog. Mark Reich of C&EN even wrote a little blurb about them in the Newscripts section for the February 8th issue that year. As a result (the lesson here being never encourage a person like me) I made some more the following year, posted them to reddit again, and had a similar (though slightly less enthusiastic) response.

This year I had some more time at home, having taken parental leave after the birth of a child. Quite literally while holding a tiny baby, I managed to make a fresh batch of five cards for Valentine’s Day 2018, and even to re-do the artwork for the original 2016 set (which originally suffered both from my childlike drawing ability and my utter lack of experience using Adobe Illustrator).

Having refrained from posting about it here for the last two years I figured now was as good a time as any to break my (very long) post drought here on the Chemistry Blog.

You can find 2018’s crop of Valentines here.

You can find all of the Valentines here, including the re-done batch from 2016.

Because nothing says “Valentine’s Day” like an endearing groan or sigh from the one you love.

Enjoy!

 

 

By January 1, 2018 1 comment fun

The Smell of Chemistry in the Morning

“May I present to you: the Smellmaster 9000.”

One of my professors once told me quite categorically that if you can smell someone’s chemistry, they are doing a bad job.  His point was that any chemist worth their salt would be doing stinky things in properly-maintained fumehoods, and never exposing themselves or their colleagues to whatever unholy stenches their reagents possessed.  To a certain extent, I agree with him.   I’ve never had to brave the foul miasmas of things like isonitriles and I never plan to, but if that eventuality arises you can be sure that I’ll do that in a fumehood.  Or possibly in a fumehood inside a fumehood.

But for most people who work in chemistry labs, the occasional waft of bizarre odours is not unusual.  Sometimes it’s even useful: a project I was doing a while back involved the consumption of phenylacetylene (which has quite a characteristic odour, somewhat similar to styrene), and doing a careful wafting test actually proved to be about as effective for determining a reaction’s completion as a TLC.  Not that everyone should smell-test all their reactions!  But the point is that working as a chemist tends to give you the peculiar ability to identify reagents by their smell, simply through familiarity caused by repeated low-concentration exposure.  The sharp fruitiness of ethyl acetate, the almond sweetness of benzaldehyde, the bitter nose-wrinkling sting of pyridine…there’s an entire world of pleasant and unpleasant smells in the world of organic chemistry, and just like everyone starts to accumulate their favourite and most-hated customers when working in retail, I have a suspicion that each chemist has their own personal list of best- and worst-smelling chemicals.  I’m sure we all remember high-school chemistry, and detecting the rancid butter stink of carboxylic acids down the hallway when people did their esterification lab, then getting to smell the artificial rum, banana, and mint flavours that resulted when they did the lab themselves.

Smells form very strong memories, and I thought it might be nice to share some of my own memorable olfactory experiences in chemistry, and see what others had to add to the conversation.

Note: I should emphasize that I did not go around shoving my nose in bottles of these chemicals, nor should you.  Please be careful with all chemistry you do, and always do it in a fumehood for your safety and that of your colleagues.

1. Pentafluorophenol.  I did some solution-phase peptide couplings a while back and had to weigh this stuff out on a regular basis.  Its physical properties leave something to be desired (so hygroscopic it appears to melt as you weigh it, highly volatile, and not exactly cheap), but its odour is something I don’t think I will ever forget in my life.  It smells almost like some non-existent overripe fruit, almost cloying in its sweetness, lingering for quite some time after being capped and removed from the weighing area.  It’s one of those smells that I wouldn’t say I enjoy, but it’s so intriguing that I also can’t say that I dislike it, either.

2.  Chloroacetyl chloride.  I love the smell of vinegar to begin with, but this stuff takes it to a whole other level.  Doing carbohydrate chemistry introduced me to this molecule and though I haven’t smelled it since it’s another absolutely unforgettable one.  It has a very similar smell to regular old acetic acid, but with this sort of appalling greasiness to it that I always found interesting and somewhat appealing.  Similar to this is trufluoroacetic acid, but not only is TFA more dangerous, its odour is so sharp at even low concentrations that it is on the whole quite unpleasant.

3. Methylindoles.  Very recently I had the regrettable task of doing some indole chemistry, and I am glad to have it behind me.  Though definitely not anywhere near the top of the all-time worst chemical smells, there is something about N-methyl, 1,3-dimethyl, and especially 2-methylindole that I cannot stand.  I had the incredibly poor judgement to open a vial of the 2-methylindole outside my fumehood and it’s safe to say that I will never make that mistake again.  Similar to that urinal-cake/mothball smell of naphthalene, yet infinitely more revolting, the smell of these compounds will linger for up to a couple hours if spilled or left open outside a fumehood (even after being cleaned up and/or capped).  The 3-methyl variety of indole, which I’ve also had the extreme displeasure of working with, is alternatively known as skatole, because it smells like…well, I think you get the idea.

4. Eugenol. Similar to the esterification lab, the extraction of this compound from cloves is a very common organic chemistry experiment in the Canadian university chemistry lab.  There’s nothing really surprising about it, because you’re extracting one of the nice-smelling compounds from an already nice-smelling spice, but I think it’s the transformation that makes this smell so interesting to me.  You go from cloves–a rich, heady smell that’s always made me think of a spicy chocolate Christmas tree–and when you isolate the eugenol the complexity vanishes, and you’re left with a single note (predictably).  The smell reminds you of cloves, but only in the way that esters remind you of their fruit counterparts.  The smell is completely one-dimensional, and though pleasant has none of the punch that freshly ground cloves do.  There’s just something about experiencing this one particular element of cloves’ smell, completely isolated, that I love.

So, fellow chemists, what olfactory adventures have your studies taken you on?  Can anyone come up with a plausible description for the legendary odour of isonitriles?  Does anyone have nuanced critiques on the qualities of sulfides and thioethers?  Have there been detailed qualitative studies on the nasal SAR of various benzaldehyde derivatives?  Or are there people out there with intimate knowledge of specific compounds whose odours they find irresistible?

Remember, knowledge is power.  And the nose knows.

By May 19, 2013 6 comments Uncategorized

Yes, it’s been done: coffee flavour chemistry

When I was much younger, and my interest in chemistry was just beginning to influence my thoughts of post-secondary school and (a lifetime away) a career, there were hints of my destiny that came in the form of somewhat perverse interests.

One of these was my profound interest in the chemical constituents of coffee. A non-chemist simply sees a cup of coffee for what their nervous system and digestive see it: a black liquid that tastes bitter, inhibits your appetite, and gives you about a two hour energy boost. However, being the child of two coffee snobs who also happened to be career scientists, I had different notions.

What makes a good cup of coffee? People have their preferred brands, countries of origin, or even vintages, if you have that much money to throw away. There are even those who eat an obscenely expensive bean that has been digested and excreted by the Asian palm civet. But can you actually taste the difference? And more importantly, what makes up the difference in flavour?

Most coffees are simply described in terms of acidity, roast, and some vague notes about other flavours (vanilla, caramel, berries, chocolate). This, to me, was completely unsatisfactory. Little did I know that coffee flavour chemistry is a legitimate field of study, as is the study of flavours and scents in general.

In my slightly-more-recent searches on the topic, I stumbled across a book entitled Coffee Flavour Chemistry; a better match for my childhood fascination could not have been conceived. Though now somewhat out of date, the book represented a major achievement in the field in 2002 when it was written by Ivon Flament, and contains some very interesting information and a comprehensive review of the work done in identifying coffee’s chemical components. It identifies over one thousand compounds present in both green and roasted coffee beans, describing their aromas and their significance in the overall flavour of the coffee. Intuitively, the most important constituents of coffee flavour are the ones with the highest “signal-to-concentration” ratio, or how easily they can be detected at a certain concentration. Some of the most important constituents can be seen below, with their described flavours:

The majority of these compounds are of course formed via the well-known Strecker degradation and the Maillard reaction.  These, as well as other important aspects of the roasting of coffee beans, are discussed within the book.

Perhaps what I found most interesting are the techniques used to determine what are called “odour activity values”, which essentially amount to a quantification of how strong a compound’s odour is at a given concentration.

The methods used for finding these values are actually gas-chromatographic olfactometry, which is exactly what you think it is: they run a GC, and have someone sniffing the end of the column, who presses a button each time they smell a compound. I laughed at this when I read it, not because it’s unreliable (quite the contrary), but because imagining running a column with a panel of “sniffers” at the end instead of a mass spectrometer is quite an image indeed.

The original method (GC-olfactometry) was purely qualitative in terms of odours, but later methods known as CHARM (a proprietary technique involving dilution-to-threshold) and AEDA (aroma extract dilution analysis, a similar method) have overshadowed it in recent years. Yet another method, named with a classic, groan-inducing acronym is “GC-SNIF”, which stands for “gas chromatography-surface of nasal impact frequency”, in which panels of test subjects are used to determine how “smellable” a compound is at a single concentration, producing averaged and normalized curves for the detection of smells.

Apart from being a funny image, these methods of analysis (which are almost always used in conjunction with purely analytical methods) illustrate an interesting point about flavour chemistry. While GC or LC data, as well as mathematical methods such as canonical analysis or principal component analysis are useful for predicting simple properties, the use of human organoleptic testing is essential to actually understanding the results.

Another salient point that was mentioned was the perception of quality. In a 1986 paper, Liardon and Spadone discovered that while the degree of coffee roasting was correlated to a large number of compounds and their concentrations, the quality of the coffee did not appear to be correlated to any of them. One of the few quantitative differences that could be established based on quality was that between green C. arabica and C. robusta beans. Robusta tended to have higher concentrations of methanol, acetone, pyridine, methylpyrazine, and furfural, and also seemed to be unique in that they contained methyl formate, t-butyl alcohol, and furfuryl alcohol, not found in Arabica strains. Robusta beans are widely perceived to be inferior in flavour and aroma to arabica beans, which is why many coffee packages will declare themselves to contain “100% arabica beans” to avoid confusion and distinguish themselves.

So what does this tell us? After skimming through the book I came away with two lessons: the first is that while computers and statistical analyses become more and more powerful every day, it seems there is usually a place for subjective human-generated data.  Without olfactory analyses from panelists, much of the work on coffee and its constituents would have been completely useless. The second is that while this data is essential to understanding the importance of certain compounds in generating a specific flavour, it is almost worthless when trying to establish a causal link between specific compounds and the perceived quality of the coffee (edit: this is not strictly true for identifying fundamental flaws in the bean due to parasites, mould, or poor growing conditions, which can all be identified by screening for certain compounds). For the most part, as everyone has heard so many times in their life: there’s just no explaining some people’s tastes.

However, I think for most of us in grad school, the fact remains that the most important compound in coffee is one which contributes almost nothing to its odour profile:

By January 23, 2011 11 comments Uncategorized