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