A bond by any other name...: How the simple definition of a hydrogen bond gives us a glimpse into the heart of chemistry

Basic hydrogen bonding between two water molecules,
with the central hydrogen shared between two oxygens

A few years ago, a committee organized by the International Union of Pure and Applied Chemistry (IUPAC) - the international body of chemists that defines chemical terms and guides the lexicon of the field - met to debate and finalize the precise definition of a hydrogen bond.

Defining a hydrogen bond in the year 2011? That was odd to say the least. Hydrogen bonds have been known for at least seventy years now. It was in the 1940s that Linus Pauling defined them as foundational elements of protein structure; the glue that holds molecules including life-giving biological molecules like proteins and DNA together. Water molecules form hydrogen bonds with each other, and this feature accounts for water's unique properties. Whether it's sculpting the shape and form of DNA, governing the properties of materials or orchestrating the delicate dance of biochemistry performed by enzymes, these interactions are essential. Simply put, without hydrogen bonds, life would be impossible. No wonder that they have been extensively studied in hundreds of thousands of molecular structures since Pauling highlighted them in the 1940s. Today no chemistry textbook would be considered legitimate without a section on hydrogen bonding. The concept of a hydrogen bond has become as familiar and important to a chemist as the concept of an electromagnetic wave or pressure is to a physicist. 

What the devil, then, were chemists doing defining them in 2011?

It turns out that behind the story of defining hydrogen bonds lies a paradigm that takes us into the very guts of the nature and philosophy of chemistry. It leads us to ask what a chemical bond is in the first place; drill down deep enough into it, and it starts appearing like one of those existential questions a Zen monk would ask about life or the soul.

Remarkably enough, in spite of the debate and redefinitions, the basic features of a hydrogen bond are not controversial. A hydrogen bond is a bond that exists between a hydrogen and two other non-hydrogen atoms. Those two other atoms are most commonly oxygen and nitrogen, but that's where the consensus seems to end and the endless debate begins.

The basic reason for the debate has to do with the very definition of a bond as laid out by pioneering chemists like Gilbert Newton Lewis, Irving Langmuir and Linus Pauling in the 1920s. Loosely speaking a bond is a force of attraction between two atoms. It was Lewis who made the groundbreaking suggestion that a chemical bond results from the donation, acceptance or sharing of electrons. Pauling codified this definition into a rigorous principle using the laws of quantum mechanics. He showed that using quantum mechanics, you could prove that the sharing of electrons between two atoms leads to a net lowering of energy between them: this sounds logical since if there were no lowering of energy, there would be no incentive for two atoms to come close to each other.

So far so good. Everyone accepts this basic fact about chemical bonds. Treatises have been written about the various bonds between different atoms seen in a bewildering array of metallic, organic and inorganic molecules; Pauling's seminal book, "The Nature of the Chemical Bond", described such interactions in loving detail. In this book he showed that bonds can be covalent or ionic; the former involve a symmetric sharing of electrons while the latter involve an asymmetric give and take. There are also many intermediate cases. Furthermore, whether a bond is ionic or covalent depends on the electronegativity of the atoms involved. Electronegativity is the innate property of an atom to hold on closely to its electrons. Fluorine for instance is the most electronegative element of all, holding on to its electrons in a fiery embrace. Metals on the other hand are happy to give away their electrons. Not surprisingly, bonds between metals and fluorine are readily formed.

It is in the context of electronegativity that it's easy to understand hydrogen bonds. A hydrogen atom, just like a metal, is happy to give away its lone electron and form a positive ion. Oxygen and nitrogen atoms are happy to accept this electron. Thus, a hydrogen bond forms when a hydrogen atom is shared between two oxygen atoms (or one oxygen and one nitrogen, or two nitrogens). Because of the difference in electronegativity, the hydrogen acquires a slightly positive partial charge, and the other atoms acquire a slightly negative partial charge (represented in the picture above). Think of two oxygen atoms with a hydrogen between them acting as a bridge: that's a hydrogen bond between them. Because a hydrogen atom is small and has only a single electron it can achieve the feat of forming this bridge; what is fascinating is that this is partly the result of a unique quantum mechanical phenomenon called the tunnel effect.

All this is rather uncontroversial. The debate starts when we ask what criteria we use to actually identify such hydrogen bonds. Chemists usually identify bonds by looking at experimental structures of molecules. The most common method of acquiring these structures is by x-ray diffraction. Bouncing x-rays off a crystallized molecule allows us to accomplish the molecular equivalent of taking a photograph. The molecules under question can be anything from common salt to complicated proteins. These structures form a cornerstone of chemistry, and they are not just of academic importance but have also been immensely useful in the design of new drugs and materials.

When chemists acquire the crystal structure of a molecule, they will usually do something very simple: they will measure the distance between various atoms. The hallmark of a chemical bond is a short distance between two atoms; think of it as two people embracing each other and reducing the distance between themselves. How short, exactly? Short enough to be less than the sum of Van der Waals radii of the two atoms. Imagine the Van der Waals radius of an atom as a kind of safe perimeter which an atom uses to hold other atoms at bay. Each atom has a unique Van der Waals radius defining its safe perimeter which is measured in the unit angstroms (1 Å = 10^-10 meters). Hydrogen for instance has a radius of 1.2 Å, nitrogen has a radius of 1.5 Å. If a chemist measures the distance between a hydrogen and nitrogen in a crystal structure as being less than 2.7 Å (1.2 + 1.5), she would usually declare that there's a bond between the two atoms. If the three atoms in a hydrogen bond satisfy this geometric criteria, then one could legitimately claim a bond between them.

But this simple procedure turns out to be far trickier to accept than we can imagine. Here's the problem: a crystallized molecule is a complex assembly of hundreds or even thousands of atoms, all of which are jostling for space. The eventual formation of the crystal is not a zero-sum game; some atoms have to give way so that others can be happy. As the pioneering chemist Jack Dunitz has succinctly noted, "Atoms have to go somewhere". Thus, some atoms are simply forced together against their will, just like people in a cramped train compartment who are forced together against their will. Now, just like those cramped people, the distance between two such cramped atoms will be unnaturally short, often shorter than the the sum of their Van der Waals radii. The key term here is "unnaturally": the distance is short not because the atoms actually want to be close, but because they are forced to be so. Can one then say that there is a bond between them? And how short does this distance need to be in order to be called a bond?

There's another conundrum that emerged as thousands of crystal structures of molecules started to appear during the last few decades. While the "classical" hydrogen atoms bridging oxygens and nitrogens were well known, short distances also started appearing between hydrogen and atoms like carbon and chlorine. The purported hydrogen bond zoo started to get populated with even more exotic creatures. For instance chemists started noticing close contacts between hydrogens and the flat face of benzene rings: these hydrogens are attracted to the ghostly electron clouds lying on top of the rings. Sometimes you did not even need a benzene ring; two doubly bonded carbon atoms would appear as magnets for hydrogens and pull them close. And these hydrogens in turn again would not just be bonded to oxygens or nitrogens as their second partners; they could be bonded to carbons, or even to metallic elements. Experimental observation forced the concept of hydrogen bonds to be extended not just to other bonafide atoms but to more abstract entities like clouds of electrons.

An illustration of two kinds of hydrogen bonds:
conventional ones with oxygen atoms in blue
and those with a benzene ring in red

Two overriding questions thus emerged from these decades-long exercise of observation and analysis: Can one claim a bond between two atoms in a molecule - specifically a hydrogen bond in case of hydrogen, oxygen or nitrogen - simply based on the distance between them? And what atoms exactly constitute a hydrogen bond?

The IUPAC committee in 2011 seems to have exorcised both demons with a single stroke. They defined a hydrogen bond as any kind of bond between a hydrogen and two other atoms, provided that the other two atoms are more electronegative than hydrogen itself. That always included oxygen and nitrogen, but now the definition was expanded to include carbon and halogens (chlorine, fluorine, bromine and iodine) as well as ghostly entities like electron clouds on top of benzene rings. As far as the distance criterion was concerned, IUPAC made a wise decision in allowing it to be fairly variable and not simply limited to a hard cutoff within the sum of Van der Waals radii.

The IUPAC decision illuminates three very important aspects of chemistry. Firstly, it tells us that many chemical concepts are fuzzy and only approximately defined. For instance, although we have defined the distance between the hydrogen and other two atoms in a hydrogen bond as being less than the sum of their Van der Waals radii, in reality these distances are best derived as a statistical distribution. Some hydrogen bonds are very short, some are very long, and most are in the middle: even this classification has been a hotbed of contention, and you will find arguments about the nature and energies of "short" and "weak" hydrogen bonds in the scientific literature that approach the vigor of gladiatorial contests. The ones that are short usually involve nitrogen and oxygen, while the long ones involve the elements included in the expansive IUPAC definition. This fuzzy reality extends to other concepts in chemistry such as aromaticity, polarizability and acid and base behavior. Unlike concepts in physics like wavelength and electrical conductivity, concepts in chemistry can be much more malleable. However this malleability is not a bug but a feature, since it allows you to capture a vast amount of chemical diversity in a central idea.

The second key aspect of chemistry that the IUPAC statement reveals is the fact that scientific concepts don't have to always be rigorously defined in order to be useful. The definition of a hydrogen bond goes to the heart of chemistry as a science based on models. A hydrogen bond is a bond, but it's really a model based on our ideas of the myriad ways in which molecules interact. The key feature of a model is utility, not reality. In my own work for instance, I can recognize and exploit hydrogen bonds between proteins and drugs and improve their directionality and strength, all without worrying one bit about their precise, rigorous definition. Similarly polymer chemists can create new forms of hydrogen-bonded plastics with novel functions without caring much whether their hydrogen bonds conform to some well-defined ideal. Whatever the debate about hydrogen bonds may be, my view of them is similar to Potter Stewart's: I know them when I see them. Or, if I wanted to offer a cheesy but still quotable line from one of "The Matrix" movies, a hydrogen bond is merely a phrase; what matters is the connection it implies.

Ultimately, this fuzzy yet useful view of hydrogen bonding makes an important statement about the philosophy of chemistry. It tells us that chemistry has its own philosophy based on models and utility that is independent of its roots in physics. As the chemist Roald Hoffmann memorably put it, chemical concepts like aromaticity and electronegativity start to "wilt at their edges" when examined too closely, and Hoffmann could have been talking about the hydrogen bond there. The physics-based view of a hydrogen bond would involve writing down the Schrodinger equation for these bonds and rigorously solving it to obtain quantities like the energy and geometry of the bond. But that exercise is too reductionist; it does not actually help me understand the nature and variety of these bonds. It won't tell me why water is liquid and why it flows from mountains, why it's a universal solvent and why it's an existential life-giver. Chemistry proclaims its own emergent language and philosophy, and while the material entities of which molecules are composed are grounded in physics, the molecules themselves belong squarely in the domain of chemistry.

The fact that chemists are still debating hydrogen bonds means that chemistry remains an exciting and vibrant discipline, one in which even basic concepts are still being sculpted and fine-tuned. It tells us that for the foreseeable future chemistry will continue to be a science without limits, a country with open borders. The hydrogen bond should give chemists an opportunity to celebrate the very soul of their work.

Science as a messy human endeavor: The origin of the Woodward-Hoffmann rules

A 1973 slide from Roald Hoffmann displaying the 'Woodward
Challenge' - four mysterious reactions which spurred the
Woodward-Hoffmann rules

There is a remarkable and unique article written by my friend and noted historian of chemistry Jeff Seeman that has just come out in the Journal of Organic Chemistry. The paper deals with seven pivotal months in 1964 when Robert Burns Woodward and Roald Hoffmann worked out the basic structure of what we call the Woodward-Hoffmann rules. 

Organic chemists need no introduction to these seminal rules, but for non-chemists it might suffice to say that they opened the door to an entire world of key chemical reactions - both in nature and in the chemist's test tube - whose essential details had hitherto stayed mysterious. These details include the probability of such reactions occurring in the first place and the stereochemistry (geometric disposition) of their molecular constituents. The rules were probably the first significant meld between theoretical and organic chemistry - ten commandments carried down from a mountain by Woodward and Hoffmann, pointing to the discovery of the promised land.The recognition of their importance was relatively quick; In 1980 Hoffmann shared a Nobel Prize for his contributions, and Woodward would have shared it too (it would have been his second) had he not suddenly passed away in 1979.

The first paper on these rules was submitted in November, 1964 and it came out in January, 1965. Jeff's piece essentially traces the conception of the rules in the previous six months or so. The article is very valuable for the light it sheds not just on the human aspect of scientific discovery but on its meandering, haphazard nature. It is one of the best testaments to science as a process of fits and starts that I have recently seen. Even from a strictly historical perspective Jeff's article is wholly unique. He had unprecedented access to Hoffmann in the form of daylong interviews at Cornell as well as unfettered access to Hoffmann's office. He has also interviewed many other important historical figures such as Andrew Streitweiser, George Whitesides and Jack Roberts who were working in physical organic chemistry at the time: insightful and amusing quotes from all these people (such as Whitesides's reference to the demise of a computer at MIT implying that he would now have to perform calculations using an abacus or his toes) litter the account. And there are copious and fascinating images of scores of notebook pages from Hoffmann's research as well as amusing and interesting letters to editors, lists of publications, scribblings in margins and other correspondence between friends and colleagues. Anyone who knows Jeff and has worked with him will be nodding their heads when they see how thorough the job here is.

The story begins when Woodward was already the world's most acclaimed organic chemist and Hoffmann was an upcoming theoretical chemistry postdoc at Harvard. Then as now, Hoffmann was the quintessential fox whose interests knew no bounds and who was eager to apply theoretical knowledge to almost any problem in chemistry that suited his interests. By then he had already developed Extended Hückel Theory (EHT), a method for calculating energies and orbitals of molecules which was the poster child for a model: imprecise, inaccurate, semiquantitative and yet pitched at the right level so that it could explain a variety of facts in chemistry. Woodward had already been interested in theory for a while and had worked on some theoretical constructs like the octant rule. It was a marriage made in heaven.

The most striking thing that emerges from Jeff's exhaustive and meticulous work is how relatively laid back Woodward and Hoffmann's research was in a sense. Hoffmann became aware of what was called the 'Woodward challenge' early in 1964 during an important meeting; this challenge involved the then mysterious stereochemical disposition during some well-known four and six electron reactions, reactions whose jargon ("electrocyclization", conrotatory") has now turned into household banter for organic chemists. The conventional story would then have had both Woodward and Hoffmann burning the midnight oil and persisting doggedly for the next few months until they cracked the puzzle like warriors on a quest. This was far from the case. Both pursued other interests, often ended up traveling and only occasionally touching base. Why they did this is unclear, but then it's no more unclear than why humans do anything else for that matter. Once they realized that could crack the puzzle however they kicked the door open. The paper that emerged in early 1965 was so long and comprehensive that they worried about its suitability for JACS in a cover letter to the editor.

Jeff's story also touches on a tantalizing conundrum whose solution many readers would have loved to know - E. J. Corey's potential role or the lack thereof in the conception of the rules, a role Corey unambiguously acknowledged in his 2004 Priestley Medal address, setting off a firestorm. Unfortunately Corey declined to talk to Jeff about this article (although he does dispute the timing of Woodward and Hoffmann's first meeting). His side of the story may never be known.

There is a lot of good stuff in the 45-page article that is worth reading about which I can only mention in passing here. Many of the actual mechanistic and technical details would be of interest only to organic chemists. But the more general message should not be lost upon more general readers: science is a messy, almost always unheroic, haphazard process. In addition, its real story is often warped by malleable memory, shifting egos, mundane oversights and blind alleys. For a long time science was described in bestselling books and newspaper articles as a determined, heroic march to the truth. These days there is an increasing number of books aimed at uncovering science's massive storehouses of failure and ignorance. But there is a third view of science - that of a journey to the truth which is more mundane, more complex, perpetually puzzling because of its mystery and perpetually comforting because of its human nature.

In this case even Jeff's exhaustive research leaves us with kaleidoscopic questions, questions that may likely remain unanswered. These pertain to Woodward and Hoffmann's occasional indifference to what was clearly a pivotal piece of research, to Corey's claim about the reactions, to the potential cross-fertilization between whatever else Woodward and Hoffmann were doing during this time and the project in question, and to the number of insights they might have imbibed from the community at large. Jeff conjectures answers to these questions, but even his probing mind provides no comforting conclusions, probably because there are none. The quote from Roald Hoffmann with which the piece ends captures the humanity quite well.

"Life is messy. Science is not all straight logic. And all scientists are not always logical. We're just scrabbler for knowledge and understanding."

Here's to the messy scrabblers.

Falsification and chemistry: What’s the rub?

Roald Hoffmann has often emphasized the limitations
of falsification for the everyday practice of chemistry

My last post on the role and limitations of falsification leads to a point I have made before: the fact that falsification is far less important for chemists than it is for, say, physicists or mathematicians. My take on the relative unimportance of falsification comes mainly from Roald Hoffmann who is as much of a philosopher of chemistry (and a poet) as a professional Nobel Prize winning chemist. He has an excellent essay called “What would philosophy of science look like if chemists built it“? in his collection of essays from last year (which I reviewed for Nature Chemistry here).

Hoffmann’s basic take on chemistry and the philosophy of science goes to the heart of what distinguishes chemistry from other sciences. Chemistry as it is practiced consists of two major activities – analysis and synthesis. The analysis part wherein you break down a substance into its constituent atoms and deduce their bonding, charge and spatial disposition is akin to the reductionist ethos of physics where you make sense of matter by taking it apart. The synthesis part of chemistry is highly creative and consists of building up complex molecules from simple counterparts. It is an activity that not only makes chemistry conceptually unique among the sciences but which has also contributed to the inestimable utility of the science in creating the material world around us. It is as much an art as a science, and one which makes chemistry very close to architecture as a practical pursuit.

Karl Popper wrote a well-known book called “Conjectures and Refutations” in which among other things, he laid out his central philosophy of falsification. A related philosophy is the hypothetico-deductive approach to the scientific method in which one formulates hypotheses and tests them. Here is what Hoffmann says about this way of thinking about science after analyzing a particular paper on the synthesis of fullerene molecules that can encapsulate hydrogen molecules. I am slightly rephrasing his words to make them more general:

“What theories are being tested (or falsified, for that matter) in a beautiful paper on synthesis? None, really, expect that such and such a molecule can be constructed. The theory building in that is about as informative as the statement that an Archie Ammons poem tests a theory that the English language can be used to construct novel and perceptive insights into the way the world and our minds interact. The power of that tiny poem, the cleverness of the molecular surgery that a synthetic chemist performs in creating a molecule, just sashay around any analytical theory-testing.” 

How is this creative act of synthesizing a novel substance exactly making and testing a hypothesis or theory? Now one may argue that even a synthesis holds the feet of certain theories of bonding (molecular orbital theory for instance) to the fire. It is certainly true that there is always some implicit assumption, some background knowledge, that underlines the synthesis of any molecule; the construction of the molecule would fail in fact if electrons did not flow in such and such a manner and if bonds did not form in such and such a manner, so of course you are testing elementary assumptions and theories about chemical bonding whenever you make any molecule. But why not go further then and say that you are testing the atomic hypothesis whenever you are conducting pretty much any experiment in chemistry, physics or biology? Or if you want to reach out even further and tread into philosophy, you could even say that you are testing the basic assumption behind science that natural laws dictate the behavior of material entities.

Clearly this definition of “falsification” is so general and so all-encompassing as to greatly vitiate the utility of the concept; try asking a synthetic chemist next time if the main purpose of his synthesis is to test or falsify molecular orbital theory. Drawing on the analogy between chemistry and architecture, it would be like saying that every time an architect is designing a new shape for a building she is hypothesizing and testing the law of gravity. Well, yes, and no.

In fact this debate again very much reminds me of the fondness for reductionism that physicists often bring to a debate about “higher order” disciplines like chemistry, economics or psychology. Molecules, people and societies are made out of atoms, they will say, which means that “atoms explain people”. I think most physicists themselves will agree as to the futility of such far-out explanations. The fact is that a concept is useful only if it has a direct, non-trivial relationship to the phenomenon which it purports to explain. Theories in philosophy, just like reductionist theories in physics, are far more relevant on a certain level than on others.

Synthesis is a creative activity, and while every synthesis implicitly and trivially tries to falsify some deep-seated fundamental law, the science and art of synthesis as a whole does not explicitly and non-trivially try to falsify any particular theory. That does not mean that falsification is absent or untrue, it just means that it’s rather irrelevant.

On Freeman Dyson, cadmium estimation and the joy of chemistry

Cadmium sulfide (the solution has a much
deeper, brilliant yellow color)

Freeman Dyson who is a hero of mine and who I have had the privilege of meeting at length several times is someone who has done a lot of interesting things during a long and fruitful life. Not only has he made brilliant, foundational contributions to many areas of mathematics, physics, engineering and astronomy but he has also written books showcasing elegant, wide-ranging, poetic prose.

If you look at Dyson's astonishingly diverse writings or talks it is easy to mistake him as a philosopher of science, a big picture thinker striding on the widest possible canvas.

But as he himself said to me during a long, one-on-one, intellectually sparkling lunch discussion last year, a lot of people think that talking about the big picture automatically makes one a philosopher. Dyson has indeed written about an amazing variety of big picture topics, from the origins of life to the colonization of space. But he also maintains that he has always been first and foremost a problem solver, someone who is much more interested in details than in grand theorizing. Whatever philosophy he manages to weave is built on a foundation of solving specific technical problems. This is partly evidenced by his work on highly technical engineering projects ranging from nuclear spaceships to nuclear reactors.

This quality would make Dyson quite comfortable in the company of chemists, since chemistry by its very nature is more a problem-solving discipline rather than a philosophical pursuit like cosmology or evolutionary biology. I was curious to know Dyson’s views on chemistry since while he has had thoughts on almost every imaginable topic, I could not really find anything by him on chemistry except for a review in Physics Today of Nobel Laureate Roald Hoffmann’s fine book “The Same and Not the Same”.

Then I remembered an excellent collection of interviews with Dyson that I found a few years ago on a website called Web of Stories. This website is a must-see for history of science enthusiasts. It features interviews with scores of famous scientists, humanists and artists from diverse disciplines. These interviews are real gems. The best thing about them is that they are long and detailed instead of two minute sound bytes; each interview lasts in total for several hours and covers most significant events in the interviewees’s life, so you get a real feel for the life and work of leading thinkers. In one of Dyson’s interviews I was delighted to find this:

“I was going to say about chemistry that Roald Hoffmann whom I got to know quite recently, who is a chemist who writes poetry and is a great character, he has the same attitude toward chemistry that I do. I mean it is the beauty of the details rather than any over-arching theory. In that way it’s very different from physics, and I had a taste for it. My taste is always more for the details than for the big picture…

…I learned chemistry from Christopher Longuet-Higgins who was already much more of an expert and more excited about chemistry than Eric James (Dyson’s chemistry teacher at Winchester College). And I remember Christopher bringing to Winchester some crystals of stannic iodide which he had made, which is the most marvelous stuff. It is a brilliant scarlet colour and it makes these beautiful scarlet crystals, and they’re also extremely heavy. If you have a little bottle full of it, it feels like lead. So that kind of chemistry I found delightful, just the sort of details of the actual stuff, rather than the theory that lay behind it.

I remember the joy when, here in Princeton, Willard Libby came on a visit once and brought along another little bottle of chemicals, which also was very heavy, and that was barium xenate, which was barium xenon oxide, which of course was an absolute revelation because nobody imagined that xenon could have compounds, being an inert gas. And it was sometime in the 1950s these compounds were discovered, and barium xenate is just such an ordinary stuff. It’s a sort of heavy white crystals which are completely stable, they don’t show any signs of anything strange and there it is. If you heat them up of course the xenon comes bubbling off…”

So there, I think Dyson would have felt right at home as a chemist. Chemists revel in solving particular problems. It’s not that they don’t care about general principles. Every once in a while someone like Linus Pauling or Alfred Werner comes along and ties together disparate threads into a neat superstructure. But the vast majority of chemical work consists of celebrating the diversity of structure and function inherent in natural and synthetic molecules. The point Dyson makes is an obvious and important one that is often lost among the clichéd caricatures of chemists bubbling frothy liquids and crystallizing colorful solids that one often sees in literature and cinema. But it’s precisely these bubbling liquids and colorful solids that endow chemistry with a palpable reality that’s often missing from more theoretical sciences.

A personal digression. I remember an episode from an undergraduate chemistry lab where we were supposed to estimate two unknown metal ions from a solution. After trying out every test in the book we could only detect copper. The other ion remained a mystery and we finally threw up our hands. That’s when the instructor revealed his trick. It turns out that the method of copper estimation that we were using involved turning the solution highly acidic with hydrochloric acid. With a smile on his face, the instructor put a single drop of the concentrated acidic solution in a large flask and then filled the flask to the brim with water, diluting the initial solution by at least a factor of ten thousand. Our eyes were glued to the flask as he passed hydrogen sulfide gas into the solution. And then, starting from the bottom and rising to the top, the flask filled up with the most beautiful yellow color that I have ever seen; it’s a sight that I will never forget. What happens is that cadmium is precipitated as cadmium sulfide only in dilute acidic solutions while for copper it’s the opposite. All our tests for detecting copper in concentrated acid missed the hidden cadmium, until it was ready to be unmasked by simple dilution.

Every chemist is familiar with this feeling of discovering something unknown, no matter how trivial or important, that actually exists; all the better if it has a brilliant scarlet or full-throated yellow color, as is often the case in chemistry. Dyson is right that there is something unmistakably reassuring, in-your-face - real – about holding a vial of something that was previously considered impossible.

The great organic chemist Robert Burns Woodward spoke of this very real quality of chemistry that helped him choose between chemistry and mathematics when he was a teenager:

“The fact is that I have always been very fond of mathematics- for one short period, I even toyed with the possibility of abandoning chemistry in its favour. I enjoyed immensely both its conceptual and formal beauties, and the precision and elegance of its relationships and transformations. Why then did I not succumb to its charms? For two reasons, I believe:

FIRST, because by and large, mathematics lacks the sensuous elements which play so large a role in my attraction to chemistry. I love crystals, the beauty of their form- and their formation; liquids, dormant, distilling, sloshing!; the fumes; the odors- good and bad; the rainbow of colours; the gleaming vessels, of every size, shape and purpose. Much as I might think about chemistry, it would not exist for me without these physical, visual, tangible, sensuous things.

SECOND, while in mathematics, presumably one’s imagination may run riot without limit, in chemistry, one’s ideas, however beautiful, logical, elegant, imaginative they may be in their own right, are simply without value unless they are actually applicable to the one physical environment we have- in short, they are only good if they work! I personally very much enjoy the very special challenge which this physical restraint on fantasy presents”

Woodward’s second reason for studying chemistry goes to the heart of the nature of empirical science, what Richard Feynman called “imagination in a straitjacket”. It’s a philosophy that drives all of science including the most rarefied theoretical ideas. Physicists often like to tell the story of how Einstein felt that “something had snapped inside” him when he saw the predictions of general relativity confirmed by observations of the perihelion of mercury. He surely must have felt the rare, once-in-a-lifetime satisfaction of a great theoretical construct being validated by a real observation that could be boiled down to a single number. We tend to think of Einstein as the great scientist-philosopher, but there he was, being ecstatic about a technical detail that was a crucial part of his magnum opus. Observing barium xenate or precipitating cadmium is not quite as momentous as confirming the theory of relativity, but I can readily imagine feeling a shiver down my spine if I had been presented with that sort of chemical evidence. Evidence that seemed to defy the impossible but which I could nonetheless hold in my hand and keep in my closet. That’s the joy of chemistry.

This is an updated version of a previous post on Scientific American.

Roald Hoffmann on the futility of classifying chemists

Roald Hoffmann has an editorial (open access!) in Angewandte Chemie in which he (mostly) gently scolds those who have criticized many of the last decade's Nobel Prizes as being "insufficiently chemical". I agree with him that any kind of preconceived expectations about who should get the Nobel Prize tries to fit chemistry into a straitjacket and denies scientists who may not have been trained in traditional chemistry departments the right to call themselves chemists.

As I have written elsewhere, it's partly the changing nature of what's considered important in chemical research that has shaped the face of the chemistry Nobel Prize since it was first awarded. With biology being the most exciting science of the twenty-first century and chemistry playing a foundational role in its progress, it is inevitable that more biologists are going to get chemistry prizes. And for those who may be uncomfortable with the prize awarded to biology-oriented research in the last decade, Hoffmann's observation that biology has been recognized much less over the last thirty years may provide some solace.

But any such qualms are beside the point. As Hoffmann says, the variety of chemistry Nobels given out over the years simply demonstrates the sheer reach of chemistry into multiple fields of biology, physics and even engineering. As we enter the second decade of the new century there's little doubt that fields traditionally associated with physics or engineering may increasingly be recognized by all kinds of chemistry prizes.

"Ubiquitin and the ribosome, fluorescent proteins and ion channels are as fundamentally chemical as metal surfaces, enantioselective catalysts, olefin metathesis, or, just to name some fields squarely in our profession that should be (or should have been) recognized, laser chemistry, metal–metal multiple bonding, bioinorganic chemistry, oral contraception, and green or sustainable chemistry."

And ultimately he emphasizes something that we should all constantly remind each other. It's a prize, awarded by human beings. It's an honor all right, but it does very little to highlight the objective value of the research which is usually evident far before the actual recognition. The fact that we were informally nominating Robert Grubbs or Roger Tsien years before they received the prizes makes it clear that no prize was really going to change our perception of how important their work was. Today we look at Tsien's research on green fluorescent protein with the same joyful interest that we did ten years ago.

Hoffmann sees the principal function of the Nobel Prize as providing an incentive for young students and researchers from scientifically underprivileged countries, and he cites the examples of Kenichi Fukui and Ahmed Zewail inspiring their fellow countrymen. The Nobel Prize certainly serves this function, but I have always been a little wary of pitching the benefits of scientific research by citing any kind of prize. The fact is that most people who do interesting research will never win the Nobel Prize and this does nothing to undervalue the importance of their work. So even from a strictly statistical standpoint, it would continue to be much more fruitful to point out the real benefits of science to young people- as a means of understanding the world and having fun while you are at it. Prizes may or may not follow.

Hat tip: Excimer

Image source