142 NATURE CHEMISTRY | VOL 4 | MARCH 2012 | www.nature.com/naturechemistry

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Zen and the art of moleculesMichelle Francl wonders what it is that makes a molecule elegant.

The oddest scientific talk I ever gave was on the quantum mechanics of intramolecular rotation in 3-trifluoromethyl phenanthrene. The molecule’s behaviour is unarguably eccentric. The trifluoromethyl rotor seems to be disordered in the X-ray crystal structure, suggesting the presence of two conformers that are close in energy. The observed disorder does not, however, stem principally from two competing minima of the rotor, instead it reflects the libration of this high-barrier rotor: the two positions observed in the X-ray solution roughly represent the limits of the libration1. But the science was perhaps the least strange aspect of the experience. For one thing, I gave the talk barefoot.

The invitation to speak had come from London-based Siobhan Davies’ dance company. The opening movement to the piece being performed, In Plain Clothes, required someone to give a technical talk on a subject of their choosing2. So instead of the usual university lecture hall venue, I was standing in the middle of a bare stage. My shoes had been left in the wings lest I ding the pristine dance floor with my high heels. No screen, no blackboard. Armed only with my notes and a three-foot-long

ball-and-stick model of 3-trifluoromethyl phenanthrene, I proceeded to give a ten minute sketch of its curious chemistry for an audience that ranged from chemistry faculty to modern-dance enthusiasts.

It’s also the only talk I’ve ever given that was reviewed in a newspaper — by a dance critic. (It made me wonder what seminar announcements would look like if, like film posters, they came with quips from the critics: “Francl…explain[s] with clarity and wit…quantum mechanics” — Philadelphia Inquirer3). In her review of In Plain Clothes, critic Ellen Dunkel remarked that the performance was “more thought-provoking than beautiful”. She wasn’t talking about the elegance of the chemistry, but what if someone were to review the science with an eye to its aesthetics?

What does make for beautiful science? Certainly it should be thought provoking. Philosophers since at least Socrates have tried to define what makes something beautiful, and the discussions haven’t become any less fraught over the centuries. Scientists, too, muse about beauty. Beautiful experiments, George Johnson proposed in The Ten Most Beautiful Experiments, are characterized by a logical simplicity4.

In compiling similar lists, physiologist Ian Glynn evinces a somewhat broader definition than Johnson: an elegant piece

of scientific work is not only simple, but ingenious, concise, persuasive,

unexpected and satisfying5, and Philip Ball sees beauty in

chemistry that unfolds with patience and exquisite attention to detail6.

I won’t pretend to have a deep grasp of the current state of the philosophy of beauty and

elegance, either in general or with respect to science in particular, but I think I

have an intuitive sense of what makes the quintessential chemical object — a molecule — beautiful. Judging by the response I got when

I posted this query on Twitter, so do many

chemists. Perforce, my own list of the ten most beautiful molecules (see Box 1) and what makes them so gorgeous in my eyes:

Azulene. Buckminsterfullerene is often cited as the most beautiful of molecules7, in large part because of its high symmetry, but on this score I consider azulene to be even more beautiful. Eighteenth-century philosopher Frances Hutcheson suggested we find symmetry appealing because it can be construed as evidence that there are discoverable patterns in the workings of the universe8. Admittedly, there is a stark beauty to symmetric objects, particularly ones of very high symmetry, such as the Platonic and Archimedean solids — C60 belonging to the latter group. Still, for larger molecules I find those with C2v symmetry to be more appealing than the higher symmetries, perhaps because they strike a balance between the baroque complexity of a completely asymmetric molecule and the monotonous repetition of elements in highly symmetric species.

Carvone. Carvone surprises, a non-superimposable mirror pair of compounds that could never be confused with one another, there is no need for sophisticated

Box 1 | Michelle’s top ten beautiful molecules.

Top row, left to right: azulene, (R)-(−)-carvone (the one that smells of spearmint), ferrocene, ethanol and vanillin. Bottom row, left to right: caffeine, the core structure of penicillin, an insulin hexamer, snoutane and cubane. Insulin image reproduced from ref. 15, © 2002 NPG.

There is beauty in chemistry that unfolds with patience and exquisite attention to detail.

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NATURE CHEMISTRY | VOL 4 | MARCH 2012 | www.nature.com/naturechemistry 143

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spectroscopy: one smells of spearmint, the other of caraway. The unexpected stands out from the noise, from the routine, a subtle reminder that there is more to life than routine. As Glynn points out, there is a certain beauty in a persuasive example5. The carvones are epitomes of the significance of chirality in biological systems, an example so striking even the non-chemist grasps that subtle changes in structure can lead to less-than-subtle changes in activity.

Ferrocene. In the eyes of a non-chemist, it’s not at all clear why the iron ‘ball’ would not roll out from between the cyclopentadienyl ‘plates.’ Ferrocene subtly makes the invisible — the haptic bonds between the aromatic rings and the metal — visible. Its beauty lies not in its outward form, but in what that form reveals about what we cannot directly experience; it leans toward what Immanuel Kant might have called sublime.

Ethanol. If my tweets are any indication, ethyl alcohol is a well of inspiration to many a chemist, but that’s not the root of my fascination with it. The Japanese aesthete sees beauty in what has been well polished by time, in the notion of sabi9. Brewing may be the oldest chemical art; my bottle of Chimay ale offers more than a soft buzz, it glows with burnished images of Trappist monks and Egyptian brewers. Ethanol has a patina of history that no other molecule can match.

Vanillin. “But when from a long-distant past nothing subsists…taste and smell alone, more fragile but more enduring, more unsubstantial, more persistent…bear unflinchingly, in the tiny and almost impalpable drop of their essence, the

vast structure of recollection”10. Novelist Marcel Proust could have been speaking of vanilla — when the tiniest drop wafts through my kitchen it raises the ghost of my grandmother — rather than the lime-blossom scent of his great-aunt’s madeleines. James Kirwan points out that beauty engages our imaginations on multiple levels8. Molecules that pull our minds beyond the lab, that insert themselves into our memories, are tinged with the beauty of that which they evoke. Vanilla’s scent overwrites its rather ordinary structure with a layer of charm, whereas the cerulean hue of azulene’s crystals (pictured) adds depth to a molecule already aglow with beauty.

Caffeine. In Plato’s dialogues on beauty, Socrates puts forth the notion that beauty

is usefulness directed towards the good. By this definition, caffeine might be the most

beautiful molecule of all to students of chemistry. How many late-night

experiments and early-morning conversations have been facilitated

by a tall mug of coffee or a bracing cup of tea?

Penicillin. For me, the striking beauty of penicillin lies not

in its molecular structure, or its extrinsic properties, but in its mechanism of action. It’s a Trojan horse

of a molecule, which opens up into a trap for unwary

bacterial transpeptidases. The chemistry is simple enough to

explain to my general chemistry class, but powerful enough to

keep my son from dying of a major staphylococcus infection.

Insulin. What other molecule has such a depth of beauty that its X-ray diffraction

pattern is part of the Victoria and Albert’s collection? (Actually several, including haemoglobin.) There is a logical simplicity to insulin — even in the electron-density map shown here. A single, well-defined and well-characterized entity that beautifully plugs a metabolic hole.

Snoutane. Seriously, I have no particular attachment to the molecule itself; it’s the name that I find so attractive (according to Leo Paquette and John Stowell, it derives from the Old English ‘snoute’ for the resemblance it bears to a crocodile’s nose11). There is a beauty in joy, to paraphrase poet John Keats, and the whimsical names that chemists give to some of their creations are evidence that chemistry, although weighty work, is also a source of pleasure and delight, and by extension, beauty.

Cubane. Twelfth-century Buddhist monk and essayist Kamo no Chōmei suggested that beauty embodied the principle of yūgen — profound grace. Japanese Nō theatre strives for yūgen in movements that seem impossible and require skill and discipline to execute in ways that seem natural. Cubane’s right angles seem impossible, and the skill and discipline required to routinely synthesize it and its derivatives are the chemists’ equivalent of Nō’s ‘grace of the dance’ — a mysterious and mad skill made to seem effortless9.

In my eyes, elegant molecules are symmetric; unexpected; revelatory of unseen mysteries; have a touch of sabi, a

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patina of history; a rich set of associations that stimulate our imaginations; useful; logically simple; sometimes whimsical — and sometimes profoundly graceful. De gustibus non est disputandum; others will undoubtedly have a different list of

beautiful molecules. I suspect that chemists would more readily agree on the criteria, than the particulars. Two decades ago, Roald Hoffmann suggested that molecular beauty subsisted in shapes that intrigue and invite investigation, in the knowledge of what a molecule might become, in what principles a molecule epitomizes, as well as in their novelty, simplicity and the decorative power of their representations12. It’s a list that need only add symmetry, as

Gábor Náray-Szabó proposed13, and a touch of Zen: sabi and yūgen, to match my own sense of chemical aesthetics.

In public, chemists are loath to name their creations, or anyone else’s for that matter, beautiful. In scouring more than a century of the Journal of the American Chemical Society, I could find not a single example of a molecule explicitly designated ‘beautiful’. Hoffmann notes that “chemistry has a special problem with awe”, working as we do on scales less grand than the size of the universe14. A problem that physics does not suffer from. I wonder if our own reticence to call attention to the beauty of our exquisitely small creations makes it difficult for the world at large to appreciate them as well. Maybe it’s time to ask reviewers of journal articles to address not just the significance of the work but how the molecules under consideration are beautiful? ❐

Michelle Francl is the Herdegen Fellow at the Chemical Heritage Foundation and is in the Department of Chemistry

at Bryn Mawr College, Bryn Mawr, Pennsylvania 19010-2899, USA. e-mail: mfrancl@brynmawr.edu

References1. Wang, W. et al. J. Phys. Chem. A 110, 3954–3960 (2006).2. http://www.siobhandavies.com/dance/dance-works/past-works/

in-plain-clothes/video.html3. Dunkel, E. Philadelphia Inquirer http://go.nature.com/l7e8jE

(7 Oct 2006).4. Johnson, G. The Ten Most Beautiful Experiments (Knopf, 2008).5. Glynn, I. Elegance in Science: The Beauty of Simplicity (Oxford

Univ. Press, 2010).6. Ball, P. Elegant Solutions: Ten Beautiful Experiments in Chemistry

(Royal Society of Chemistry, 2005).7. Aldersey-Williams, H. The Most Beautiful Molecule: The Discovery

of the Buckyball (Wiley, 1995).8. Kirwan, J. Beauty (Manchester Univ. Press, 1999).9. Parkes, G. Japanese Aesthetics. The Stanford Encyclopedia of

Philosophy (Winter 2011 edition) (ed. Zalta, E. N.); http://plato.stanford.edu/archives/win2011/entries/japanese-aesthetics/

10. Proust, M. Remembrance of Things Past Vol. 1 (Random House, 1981).

11. Paquette, L. A. & Stowell, J. C. J. Am. Chem. Soc. 93, 2459–2463 (1971).

12. Hoffmann, R. J. Aesthet. Art Critic. 48, 191–204 (1990).13. Náray-Szabó, G. Symm. Cult. Sci. 19, 415–423 (2008).14. Hoffman, R. in Beyond the Finite: The Sublime in Art and Science

(eds Whyte, I. B. & Hoffmann, R.) Ch. 9 (Oxford Univ. Press, 2011).15. Brannigan, J. A. & Wilkinson, A. J. Nature Rev. Mol. Cell Biol.

3, 964–970 (2002).

In my eyes, elegant molecules are symmetric; unexpected; revelatory of unseen mysteries; have a patina of history…

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