Test Cases for Hydrogen Bonding

As mentioned earlier, @aerkiaga is working now on hydrogen-bond rendering.

We’re curious for some test cases, e.g., geometries or chemistry that should be hydrogen bonds (e.g., distance, angle, atoms) and should not be detected as hydrogen bonds.

Any suggestions or files?

The pull request in progress is here, which should link to some test builds:

  • Do you want to relay a seminal publication about this large topic? If so, Margaret Etter’s article Encoding and decoding hydrogen-bond patterns of organic compounds in Acc. Chem. Res. 1990, 23, 120–126 (https://doi.org/10.1021/ar00172a005) is a go-to; she wasn’t the first in the field but the systematic notation popularized by her is very much in use e.g., in crystallography to describe supramolecular architectures

    (image credit to M. Etter, 1990ACR120)

  • Search by +hydrogen +bond in the search box in common for IUCr’s publications equally accesses the Acta Cryst series:

    A sub set of the then listed publications deal with the description of specific cases where the underlying model data are typically deposit as .cif files in the CSD file of CCDC. Beside the mask for the occasional search, the subscription based interfaces webcsd, conquest, and Python API are really worth the time invested to get familiar enough with them. A complementary data repository is e.g., the crystallography open database (COD) of data derived from diffraction experiments.

    (image credit to Shaibah et al., 2020ActaCrystE1629, a typical publication featuring the pattern of hydrogen bonding (link, open access).

Thanks, we’ll certainly use some of these. I suspect we’ll need to be fairly flexible.

For example, Stefano Forli at Scripps published this last year:

J. Chem. Theory Comput. 2020, 16, 4, 2846–2856:

By quantifying directionality, we show that there is no correlation with strength; therefore, these two components need to be addressed separately. Results demonstrate that there are very strong HB acceptors (e.g., dimethyl sulfoxide) with nearly isotropic interactions and weak ones (e.g., thioacetone) with a sharp directional profile. Similarly, groups can have comparable directional propensity but be very distant in the strength spectrum (e.g., thioacetone and pyridine). Results provide a new perspective on the way HB directionality is described, with implications for biophysics and molecular recognition that ultimately can influence chemical biology, protein engineering, and drug design.

Oh sorry if the illustration conveys the idea hydrogen bonds cross space only like as straight and direct like bar magnets. This perspective is simple and narrow yet often too narrow.

For one, programs account for this when defining when a potential couple of H donor and acceptor are close enough (counting Angstrom). E.g. in CCDC’s full Mercury program which highlights close contacts differently from hydrogen bonds, one had the option to specify further tolerance for both distance and angle:

(image credit to Yale’s user guides. It is good that the screen photo is about an elder version of Mercury, because this option was made available for long.).

Briefly glancing over the publication you indicate, considering hydrogen bonding as more complex as just a vectorial property reminds me to the approach to compute Hirshfeld surfaces between the molecules in the crystalline state: contrasting to van der Waals surfaces one may tabulate and subsequently quickly apply, this type of surface is a frontier between two molecules where the electron density between the two passes the minimum. Thus, it depends on acceptor, donor, and geometry how far out (from perspective of the central molecule) this minimum of pro-molecule electron density is reached.

Mark Spackman, Dylan Jayatilaka and their co-workers (University of Western Australia) eased access to this type of analysis of interactions with distribution of their CrystalExplorer. One result is publications’ illustrations tend to widen the sector where the interactions of hydrogen bonding are significant:


(image credit to Bosch et al., 2021ActaCrystC458, Conformational control through co-operative nonconventional C—H⋯N hydro­gen bonds