Paul Schleyer: Among the last of the universalists

I was saddened to hear of the passing of Paul Schleyer, not exactly a household name among non-chemists but someone who was undoubtedly one of the most prolific and towering chemists of his time. Schleyer started out in synthetic physical organic chemistry and then moved to computational and theoretical chemistry. Starting out at Princeton, he moved to Erlangen in Germany and finally settled down at the University of Georgia, helping to make each one of these centers a leading hub for theoretical chemistry.

Schleyer was definitely one of the last universalities - at least in the theoretical territory of chemistry - and had a definitive grasp of almost every aspect of the field; from NMR spectroscopy (he came up with the valuable NICS metric for chemical shifts) and ab initio quantum chemical calculations to non-classical carbocations, lithium compounds and strained hydrocarbon synthesis (he synthesized adamantane, for instance). Most people are content to be experts in one or two fields, but it's probably not an exaggeration to say that Schleyer was close to being an expert in most of these fields. During his career he also seems to have co-authored papers and books with virtually every prominent figure in the field, from George Olah to John Pople to Jack Roberts. His publications on these and other parts of chemistry were prolific and deep, and he was also not one to shy away from spirited debate. I had the pleasure of watching him give a talk once and it was clear that he was a formidable opponent whose knowledge of chemistry would almost always supersede that of his 'adversaries'.

In fact that last aspect of his personality was on full display the first time I encountered him. This was as a graduate student when I came across a charming and very readable account of his debate with Herbert Brown on the infamous and invaluable non-classical carbocation debate. Titled "The Non-Classic Ion Problem", this little book is structured as a series of points and counterpoints in every chapter offered by Schleyer and Brown. The constant back and forth, the dissection of minutiae of solvents, reaction rates and spectroscopy, and the general unyielding yet cordial personalities of the two men are fascinating to watch. It's pure, unadulterated scientific debate at its best.

Schleyer was definitely one of the last and greatest practitioners of the golden era of physical organic chemistry, a time when chemists dedicated their lives to exploring the fundamentals of chemical reactions and structure with vigor and rigor. He is one of a handful of figures on whose shoulders we all stand and will be genuinely missed.

Gernot Frenking is not happy...not at all

Stable is simply "able" with a "st"



Wow. This is a first for me. Three of the heavyweights in theoretical and computational chemistry have published a set of prescriptions in Angewandte Chemie for theoretical chemists claiming to have discovered new, "stable" molecules. In response, Gernot Frenking who is a well-known chemist himself has not just published a piercing and trenchant critique in reply to this article, but they actually seem to have reproduced the text of his referee's comments as a reply. This is a lively and extremely readable debate.

In an article asking for more "realism" from theory, the three heavyweights- Roald Hoffmann, Paul von Schleyer and Henry Shaefer III- have basically come up with a roster of suggestions in response to what they see as the rather flippant declarations by theoretical chemists of molecules as "stable". One of the annoying things about theoreticians is that they regularly analyze molecules and proclaim them as stable. Experimentalists then have to sweat it out for years to actually try to make these molecules. Frequently such molecules are stable under rather extreme conditions, for example in gas phase at 4 degrees kelvin. To address the animosity that experimentalists feel against such carefree theoretical predictions, the three chemists have come up with suggestions for publication.

They make some interesting points about criteria that should be satisfied when declaring molecules as stable. In fact they think that one must do away with the word "stable" and replace it by the words "viable" and "fleeting". For example for "viable" molecules, one has to be clear about the difference between thermodynamic and kinetic stability. Molecules described as viable by theoreticians must have half lives of about a day, must be isolable in condensed phases at room temperature and pressure, and must not react easily with oxygen, nitrogen and ozone (?). Molecules with more than +1 positive or negative charge must also be included with "realistic" counterions. Molecules must even be stable under conditions of some humidity. The authors then also make suggestions about reporting accuracy and precision, and about the well-known fact that theoretically reported precision cannot be more than experimentally measured precision.

If theoreticians think these suggestions are asking for too much, they have a friend in Gernot Frenking.

Frenking batters these suggestions down by basically launching two criticisms:
1. The suggestions are too obvious and well-known to be published in Angewandte Chemie
2. The suggestions are heavily biased towards experimentalists' preferences
As Frenking puts it, he expected to walk into a "gourmet restaurant", and was served a "thin soup" instead. Ouch.

I have to say that while the suggestions made by the three prominent scientists are quite sound, Frenking's points are also well-taken. He lambasts the suggestions that realistic counterions should be included in the calculation of a molecule with multiple charges; there are already molecules with multiple charges predicted to be theoretically stable which were then isolated by experiment. Ionic molecules with charges more than + or -1 are easily isolated in condensed phases. And one of the central questions Frenking asks is; why does a molecule need to be so experimentally stable in order to justify the publication of its theoretical existence. After all there are many molecules present in interstellar space which cannot be isolated under average Joe lab conditions. Under these circumstances, Frenking is of the opinion that the distinction between "viable" and "fleeting" is "eyewash" (it's the European way of euphemism)

I resoundingly agree especially with this contention, harsh as it sounds. Why should experimentalists get an easy pass? The whole point of theory is to push the boundaries of what's experimentally possible. To suggest that one should only publish a theoretical prediction if it can easily be verified by experiment is to do disservice to the frontiers of science. While I can understand the angst that an experimentalist may feel when he sees an unusual molecule stable only under extreme conditions declared by a theoretician as "stable", that's exactly the challenge experimentalists should be up to, to devise conditions under which they can observe these short-lived molecules. If they do this they are the ones who carry the day. Since stability as is well-known is a relative term anyway, why insist on calling something "stable" only if it satisfies the everyday lab conditions of the experimentalist. I believe that it is precisely by testing the extreme frontiers of stability that chemistry progresses. And this can be done only by making things hard for experimentalists, not easy. Theoreticians pushing experimentalists and vice versa is how science itself progresses, and there is no reason for either one of them to quit questioning the boundaries of the others' domain.

There are other points and criticisms worth reading, include other referee comments which endorse the article and are also quite interesting. In the end however, I cannot answer Frenking's central question; should this article have been published in Angewandte Chemie? We should leave it for readers to judge.

Roald Hoffmann, Paul von Ragué Schleyer, Henry F. Schaefer III (2008). Predicting Molecules - More Realism, Please! Angewandte Chemie International Edition, 47 (38), 7164-7167 DOI: 10.1002/anie.200801206

Gernot Frenking (2008). No Important Suggestions Angewandte Chemie International Edition, 47 (38), 7168-7169 DOI: 10.1002/anie.200802500