The C-h···o hydrogen bond:  structural implications and supramolecular design.

The C-H‚‚‚O hydrogen bond is so well-established in structural chemistry that it seems difficult now to believe that when Sutor proposed the existence of this type of hydrogen bond in the early 1960s,1,2 her suggestion was drowned in scepticism, if not outright hostility.3 It was only two decades later, with Taylor and Kennard’s paper, that the subject was properly revived.4 Shortly thereafter, an Account appeared from this laboratory describing the role of the C-H‚‚‚O interaction in crystal engineering.5 Subsequently, one felt confident enough to term these erstwhile “interactions” hydrogen bonds, in a second Account.6 A recent invitation to contribute another Account and the many recent efforts in this direction by my students and postdoctorals have led to the present paper. It is clearly no longer necessary to justify the relevance of C-H‚‚‚O hydrogen bonds, so widely invoked are they in small-molecule and biological crystallography. The presence of O-atoms in a large majority of organic molecules means that this hydrogen bond is widespread, even if not identified in many cases. However, other questions concerning these weak hydrogen bonds could be posed: (1) What is their upper distance limit? (2) Are very short, bent bonds significant? (3) Why do C-H‚‚‚O bonds sometimes disturb the strong O-H‚‚‚O and N-H‚‚‚O network? Alternatively, why do hydrogen bond donors and acceptors not always pair in descending order of strength? (4) How important is cooperativity for weak hydrogen bonds? (5) Are C-H‚‚‚O hydrogen bonds responsible for crystal packing, or are they the forced consequences of packing? (6) Are weak hydrogen bonds robust enough for supramolecular synthesis and crystal engineering? (7) Does the C-H‚‚‚O hydrogen bond have any biological significance? These difficult questions cannot be answered fully. This Account attempts to address some of them, but better answers can only follow from further work.