The only existing O-H...F-C bond...not

This is a beautiful piece of data re-interpretation. A few years ago, there was a report published about a compound which supposedly demonstrated the only instance of a solution O-H...F-C hydrogen bond. This seemed to provide some support for hydrogen bonding involving fluorine.

Now a Spanish group has published a nice paper in CC that provides a refutation and re-interpretation of the data that along with some calculations, indicates that the observed data is not due to a C-F...H-O hydrogen bond, but simply due to steric hindrance that makes the three fluorines of a CF3 group non-equivalent. In the former interpretation, it was assumed that the non-equivalence of two Fs of this group with the third F indicated that the third F was involved in hydrogen bonding. The new interpretation says that it is steric hindrance that prevents rapid rotation of the CF3 group, and makes the three Fs non-equivalent. Calculations support the interpretation.

Thus, now we will have to look for other instances in which there is bonafide C-F...H-O bonding. Quite a neat piece of careful data analysis supported by crystallography and quantum chemical caclulations.

Another fact mentioned in the paper reminds me of one of the more memorable papers that I have read; Stanford's Eric Kool's demonstration that difluorotoluene- an isostere of thymine in which Ns are replaced by Cs and Os are replaced by Fs- behaves like thymine when DNA polymerase inserts it opposite adenine.

Reference:
Is there any bona fide example of O–HF–C bond in solution? The cases of HOC(CF3)2(4-X-2,6-C6H2(CF3)2) (X = Si(i-Pr)3, CF3)
Chem. Commun., 2007, 4384 - 4386, DOI: 10.1039/b710304b

Who is the fairer one; H or X?

There's a fair amount of discussion going on at Kinasepro and TotMed regarding halogen bonding, a pretty interesting topic. I have read a few reports about it, but questions still linger. One of the questions raised by a commenter at KP was "How can a X-bond (halogen bond) be as strong as a H-bond?".

With good timing, there is a paper just published in JACS that seeks to investigate that kind of issue. It deals with competition between X and H bonding. The authors considered the four relatively simple molecules shown above that are studded with strong H-bond acceptors (pyridinyl and imidazolyl N), weak H-bond donor (imine C-H) and weak and halogens as X-bond acceptors and donors. Three of the molecules were the same except for different halogens.

The authors obtained several crystal structures, of the molecules themselves, as well as their complexes with the other molecules. The results indicate that a strong-strong H-bond donor-acceptor interaction (imadazole/pyridine N...OH hydrogen) trumps any X-bonding interaction, which is probably not too surprising. Weak X...X and N...X interactions such as Br...Br and N...Br are also trumped by weak-strong H-bonding interaction (imine C-H...pyridine N). However, N...I interactions do seem to be able to trump imine C-H...pyridine N interactions, although not strong-strong H-bonds.

Does this prove the general case of most X...X or X...N bonds being weaker than H-bonds? Yes, but not in the context of a crystal really, because crystallization is a hideously complex phenomenon to predict since it involves many subtle interactions and the sum of their costs and benefits. In a crystal or a protein for that matter, a H-bond could very well be sacrificed for a X-bond, not because the X-bond is per se stronger than the H-bond, but because the other parts of the molecule could interact in a way that is more favourable in the orientation with the X-bond rather than the H-bond.

It would also have been nice if they had mixed together the different halogen containing molecules. And I am still waiting for a good theoretical chemist to explain how the interaction can be worth 4-5 kcal/mol.

Reference:
Structural Competition between Hydrogen Bonds and Halogen Bonds
Christer B. Aakeröy,* Meg Fasulo, Nate Schultheiss, John Desper, and Curtis Moore
J. Am. Chem. Soc., ASAP Article 10.1021/ja073201c

Book review- The Weak Hydrogen Bond: In Structural Chemistry and Biology

The Weak Hydrogen Bond: In Structural Chemistry and Biology (International Union of Crystallography Monographs on Crystallography, No 9),
By Gautam R. Desiraju, Thomas Steiner
Oxford University Press, USA; Reprint edition (July 16, 2001)

Chemistry is all about interactions, and chemists have traditionally classified interactions into various categories such as covalent and ionic, hydrogen bonding and Van der Waals. But this classification is primarily for convenience, and there are many borderline cases which any chemist should be aware of, if he wants to notice interesting phenomena.

One such borderline interaction that is very important in maintaining the structure of crystals is the weak hydrogen bond. Crystallographers are in a unique position to observe and catalog such an interaction, because they are constantly looking at structures frozen in time in the solid state. These are also structures that represent the dazzling chemical diversity inherent in nature. In this book, the authors, both of whom are leading authorities in the field, provide a comprehensive and extremely readable overview of this unique interaction, which should challenge the traditional wisdom of any chemist, and should allow him or her to greatly expand his or her horizons in the world of molecular interactions.

The book starts with a lucid and excellent introduction to what are usually described as 'normal' and 'strong' hydrogen bonds. The authors then gracefully demonstrate in the rest of the book by virtue of countless examples of organic, organometallic, and biological structures, how the strong and all important traditional picture of a hydrogen bond smoothly transitions to the domain of the weak hydrogen bond. Many of the rules that chemists usually apply to the notion of the hydrogen bond need to be modified and challenged, and excursions into weak hydrogen bonds actually exemplify the whole paradigm of weak intermolecular interactions. The authors explore all the evidence for such weak interactions including statistical, energetic, and spectroscopic. The crystal structures included reinforce the astonishing variety of molecular structures around us, both artificial as well as natural. There is also great simplicity in some of these structures, which makes them and the interactions in them truly beautiful to comprehend, in terms of their stability and symmetry. The discussion in every chapter is lucid, to the point, and shows the authors' own appreciation of their subject and its ramifications.

Their discussions drive home the point that chemists always need to think in terms of a continuum of interactions, if they truly want to understand the nature of molecules. In today's specialized compartments, with rigid definitions and rules, chemistry is often perceived as a science with rigid boundaries. This is far from being the case, and the weak hydrogen bond is a superb vehicle for demonstrating the continuous nature of the science. It also demonstrates the much more general paradigm of always thinking in terms of all kinds of interactions, 'strong' and 'weak', which any chemist, no matter what his specialty, has to appreciate. More than anything else, the study of such weak interactions proves that chemistry is still very much an art with many thin boundaries between concepts, and not just a science. It is not an exact science like physics, but it is precisely this ambiguity in it which nonetheless can be classified, that makes it a unique discipline. This book is a striking example of this fact.